CHEMICAL ENGINEERING METHODS AND TECHNOLOGY HOMOGENEOUS CATALYSTS: TYPES, REACTIONS AND APPLICATIONS No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services. CHEMICAL ENGINEERING METHODS AND TECHNOLOGY Additional books in this series can be found on Nova’s website under the Series tab. Additional E-books in this series can be found on Nova’s website under the E-book tab. CHEMICAL ENGINEERIN NG METHODS S AND TECHN NOLOGY HOMOG GENEO OUS CATALY A YSTS: TYPES S, REA ACTION NS AND D APPL LICATI IONS ANDREW W C. POE EHLER EDITOR Nova Scien nce Publishe ers, Inc. N York New Copyright © 2011 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631-231-7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers’ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book. LIBRARY OF CONGRESS CATALOGING-IN-PUBLICATION DATA Homogeneous catalysts : types, reactions, and applications / editor, Andrew C. Poehler. p. cm. Includes index. ISBN 978-1-61324-749-5 (eBook) 1. Catalysts. I. Poehler, Andrew C. QD505.H647 2010 660'.2995--dc22 2010043903 Published by Nova Science Publishers, Inc. New York CONTENTS Preface Chapter 1 Metallic Nanoparticles Nanocomposites: Their Catalytic Applications Rocío Redón, N. G. García-Peña and F. Ramírez-Crescencio Recent Evolution of Oxidation Catalysis by Mo Complexes Carla D. Nunes and Pedro D. Vaz Homogeneous Catalysts Based on Bis(imino)pyridine Complexes of Iron, Cobalt, Vanadium and Chromium: The Kinetic Peculiarities of Ethylene Polymerization N.V. Semikolenova, A.A. Barabanov, L.G. Echevskaya, M.A. Matsko and V.A. Zakharov Rational Design of Chiral Ruthenium Complexes for Asymmetric Hydrogenations Jiří Václavík, Petr Kačer and Libor Červený Supramolecular Gel Catalyst: Bridging Homogeneous and Heterogeneous Catalysis Jianyong Zhang and Stuart L. James Glycerol as a Sustainable Solvent for Homogeneous Catalysis Adi Wolfson, Christina Dlugy and Dorith Tavor Homogeneous Catalysis in Carbonylative Coupling Reactions Pawan J. Tambade, Yogesh P. Patil and Bhalchandra M. Bhanage Synthesis, Characterization and Catalytic Stud of Oxovanadium (IV) Complexes with Tetradentate Schiff Bases A.P.A. Marques,, E.R. Dockal, Ieda Lucia Viana Rosa and F.C. Skrobot Unique Design Tools for the Synthesis and Design of Dendrimers as Supports for Recoverable Catalysts and Reagents and their Applications in Asymmetric Synthesis Ashraf A. El-Shehawy vii 1 43 Chapter 2 Chapter 3 97 Chapter 4 127 Chapter 5 155 185 205 Chapter 6 Chapter 7 Chapter 8 233 Chapter 9 247 vi Chapter 10 Contents Recent Strategies in Phase Transfer Catalysis and its Application in Organic Reactions P.A.Vivekanand and Maw-Ling Wang Hexenoic Acids and their Derivatives – Preparation using Selective Homogeneous Catalysts Libor Červený and Eliška Leitmannová Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids C.F. Liu, A.P. Zhang, W.Y. Li, W. Lan and R.C. Sun Palladium Complexes of N-Heterocyclic Carbenes in Homogeneous Catalysis and Biomedical Applications Chandrakanta Dash and Prasenjit Ghosh Methods for Enhancing the Activity and Selectivity of Homogeneous Catalysts in the Oxidation Processes Ludmila I. Matienko, Larisa A. Mosolova and Gennady E. Zaikov 325 Chapter 11 371 Chapter 12 387 Chapter 13 403 Chapter 14 463 499 Index PREFACE In chemistry, homogeneous catalysis is a sequence of reactions that involve a catalyst in the same phase as the reactants. Topics discussed in this book include the catalytic applications of metallic nanoparticles nanocomposites; olefin oxidation chemistry based on Mo catalysts; homogeneous catalysts based on Bis(imino) pyridine complexes of iron, cobalt, vanadium, and chromium; Ru catalysts in asymmetric hydrogenation; supramolecular gel catalysts; glycerol as a sustainable solvent for homogeneous catalysis; homogeneous catalysis in carbonylative coupling reactions and methods for enhancing the activity and selectivity of homogeneous catalysts in the oxidation process. Chapter 1 – More than a simple review, this is a compilation of what has been done so far in relation to metallic nanoparticle-polymer composites with applications in catalysis reported up to now. The authors are going through all the transition metals from scandium to the noble metals to the copper group. Also, they report that, basically, the noble or platinum group metals are the metals commonly used as catalysts although some of the others have been proven to work as catalysts on different reactions. Chapter 2 – For 80% of all compounds produced in chemical and pharmaceutical industry at least one catalytic step is essential during their synthesis. Catalysts speed up chemical reactions but can be recovered unchanged at the end of the reaction. They can also direct the reaction towards a specific product and allow reactions to be carried out at lower temperatures and pressures with higher selectivity towards the desired product. This is a principle that is pursued with increasing emphasis and dedication leading to far more specific and cleaner processes. Homogeneous catalysts, on the other hand are usually complexes, which consist of a metal centre surrounded by a set of organic ligands. The latter impart solubility and stability to the metal complex and can be used to tune the selectivity of a particular catalyst towards the synthesis of a particular desirable product. By varying size, shape and electronic properties of the ligands, the active site at which the substrate binds can be constrained in such a way that only one of a large number of possible products can be produced. Oxidation catalysis is a quite important transformation in both industrial and academic aspects. Within this field, catalysts, ranging from a variety of available metal centered systems, which rely on Mo are one of the most important. Traditionally, oxidation catalysts are based on metal oxides, holding M=O moieties, with the metal center lying in high oxidation state. A large number of important chemical reactions are catalyzed by MoVI complexes. Inclusively, several industrial processes such as viii Andrew C. Poehler ammoxidation of propene to acrylonitrile, olefin epoxidation (ARCO and Halcon processes), and olefin metathesis reactions are carried out over molybdenum catalysts. Furthermore, as molybdenum is highly available to biological systems, the coordination chemistry of MoVI has stimulated considerable interest in view of its biochemical relevance, and many MoVI complexes have been studied as models of molybdoenzymes. In recent years the development of new approaches to prepare new and stable catalyst has turned to low oxidation state MoII organometallic complexes. These pre-catalysts proved to be quite adequate to the purpose by being highly active and selective in the epoxidation of olefins and in oxidation of other substrates. Additionally, such pre-catalyst complexes are more stable towards air and moisture which allows easier handling. This chapter lights up some recent advances on olefin oxidation chemistry based on Mo catalysts with special focus on the development of new approaches to achieve active catalysts. Chapter 3 – The family of highly active ethylene polymerization catalysts based on the complexes of transition metals with bis(imino)pyridine ligands has been intensively studied in the last ten years. In this study the authors summarize the known data and present new kinetic results on the ethylene polymerization over homogeneous catalysts based on Fe(II), Co(II), V(III) and Cr(III) bis(imino)pyridine complexes with close ligand framework (2,6-(2,4,6R3LMeCln, where R= H, Me, i-Pr, t-Bu, L=(C6H3N=CMe)2C5H3N, M= Fe(II), Co(II), V(III), Cr(III), n=2,3). The effects of the activator nature (different samples of methylalumoxane (MAO), or aluminium trialkyls) and polymerization conditions on the activity of these complexes and the resulted PE structure (molecular weight, molecular weight distribution, content of methyl and vinyl groups) have been studied. For the first time the number of active centers and propagation rate constant for ethylene polymerization with Fe(II), Co(II), Cr(III) and V(III) bis(imino)pyridine complexes, activated with MAO and Al(i-Bu)3, have been determined using method of polymerization inhibition by radioactive carbon monoxide (14CO). The experimental data obtained in comparable conditions have shown that the catalytic properties of bis(imino)pyridine complexes ( polymerization activity, number of active centers and propagation rate constant, copolymerization reactivity, composition of optimal activator, formation of single site or multiple sites catalytic system, catalysts thermal stability and PE structure) are mainly determined by transition metal center of complex. The size of the substituents R in 2,6-positions of arene ring in the ligand L affects the number of active centers and molecular weight of PE as well. Chapter 4 – Thorough optimization of reaction conditions for maximum yield is the essential prerequisite of every reaction conducted on an industrial scale. In the field of asymmetric chemistry, an additional yield requirement arises, i.e. the stereoselectivity of the reaction. The plethora of fine chemical products available on the world market indirectly demands constant improvements in the production processes and literally dictates an individual, made-to-measure solution for the best efficacy. The relentless expansion of the product range thus demands rapid but reliable tools for finding the optimal reaction conditions for a synthesis of the chiral product in question. Naturally, there is no catalyst to suit all substrates. Much like enzymes, almost every reaction requires at least a slightly modified catalyst or reaction conditions. Trial-and-error syntheses and subsequent testing of all (at first sight) potentially effective catalysts are as costly and time consuming as traditional combinatory methods, due to immense possibilities Preface ix of the catalyst and substrate structures. Many of the complexes prepared by these laborious procedures finally prove ineffective when trying to utilize them in a stereoselectively catalyzed reaction. Therefore, the objective is to synthesize only those truly offering the desired behaviour. While only a few metal centres can be used effectively (namely Ru, Rh, Os, Ir), the auxiliary ligands offer infinite solutions of key changes to the structure. The rational design has become a well-known term to describe the process of fine-tuning the ligand. Although this chapter focuses on Ru catalysts, Rh complexes are also mentioned, owing to the high parallelism of these two coordination centres in the field of asymmetric hydrogenation. The term “rational design” comprises the practice of altering the molecular structures aided by computational modelling. Bearing in mind the structure of the chiral product, an experienced theoretical-organic chemist should be able to assemble a well-founded series of ligands offering good possibilities of achieving the desired performance in a particular situation. This process involves a competent rejection of structures with a significant potential of failure with regards to enantioselectivity. Given the vast number of possibilities, such a process would ideally be performed automatically, i.e. either by high-throughput experimentation (HTE) techniques, which have been amply reviewed [1] and are not covered within this chapter despite their rapid development in recent years, or through computational chemistry. This preliminary virtual assay is often referred to as in silico screening. Recently, high-capacity virtual ligand libraries have been created and analyzed, allowing a systematic description of existing ligands and a subsequent prediction of the properties of analogues. Computational methods on various levels of complexity are available, enabling us to refine the search results by stepwise reduction of the number of potentially successful catalysts by employing more sophisticated techniques. Nevertheless, it ought to be noted that empirical findings still maintain an inimitable and supreme role. Molecular modelling is doubtless a powerful tool but one needs to appreciate that even models of the highest accuracy are still an approximation and will never yield 100% match. Nowadays, there are thousands of ligands used in asymmetric syntheses and millions of further possibilities. Nonetheless, the reader is advised to note that this chapter concentrates on those used in asymmetric hydrogenation. Ligands used for asymmetric hydroformylation, hydrocyanation, reductive amination, allylic alkylation, hydrosilylation etc., are not covered. Occasionally, however, some of these are mentioned as explanatory references that may be applied to all ligands, including those for hydrogenation. Chapter 5 – Supramolecular gels have received growing attention in recent years. They represent a novel type of soft materials which may find application in various aspects. Various organogels and metallogels offer rich possibilities for catalysis. Supramolecular gels can be used in catalysis by incorporating a catalytically active unit as part of the gelator. There are three strategies in literature: 1) catalysis by discrete gelators; 2) catalysis by coordination polymer gelators; 3) catalysis by post-modified gels. Unique new catalytic properties can arise from combining gels with catalytically active centres. Interestingly supramolecular gels show enhanced activity compared with their homogeneous analogues in a number of cases. They exhibit some combined advantages of homogeneous and heterogeneous catalysis. Chapter 6 – With its promising physical and chemical properties, glycerol can be used as a sustainable solvent in many catalytic and non-catalytic organic reactions. Polar and non- in certain reactions such as the catalytic transferhydrogenation of various unsaturated organic compounds and the transesterification of alcohols. Palladium-catalyzed carbonylation reactions of alkenes/alkynes. The Schiff base ligands were characterized by elemental analysis. melting points. Furthermore. aromatic halides with different nucleophiles have undergone rapid development since the pioneering work of Reppe and Heck. phenoxycarbonylation. The carboxylic acid and its derivatives like amides. melting points. Chapter 7 – Carbon monoxide is a ubiquitous molecule in organometallic chemistry and an important feedstock in multiple catalytic processes both at the laboratory and industrial levels.N’-bis(salicylidene)-1. pharmaceuticals. Herein. thioamides etc. electronic spectroscopy and 1H and 13C Nuclear Magnetic Resonance spectra. and other industrial products. and supercritical carbon dioxide or through distillation. carbonylative Suzuki coupling reaction. Using glycerol as a solvent also enabled catalyst recycling. In addition. carbonylative Sonogashira coupling reaction etc. The oxidation catalytic of methyl phenyl sulfide with the complexes in solution and heterogeneisated by means of supporting on alumina was studied. and microwave-promoted reactions. esters. have been explored using palladium as a catalyst of choice. emulsion-like systems. Glycerol also enabled easy isolation of the reaction product either by extraction with glycerol immiscible solvents such as diethyl ether. characterization and catalytic study of Oxovanadium (IV) complexes and yours precursors Schiff bases [N. methyl phenyl sulfoxide. inorganic compounds. glycerol was used as both solvent and reactant. The scope of carbonylation reactions is also extended for the synthesis of pharmaceuticals and their important intermediates using carbonylation as the key step using homogeneous catalysis. and ketones prepared in this way are important intermediates in the manufacture of dyes. the catalytic products were characterized by 1H Nuclear Magnetic Resonance and Fourier Transformed Infra-red spectroscopy. The term carbonylation covers a large number of closely related reactions that all have in common that carbon monoxide is incorporated into a substrate by the addition of CO to an aryl-. The catalytic reactions were accompanied by gas chromatography. Poehler toxic. recyclable liquid that is manufactured from renewable sources and that facilitates the dissolution of organic substrates. such that nowadays plethora of palladium catalysts and various synthetic protocols are available for the synthesis of aliphatic and aromatic carboxylic acids as well as their derivatives. aminocarbonylation.3-phenylenediamine] and [N. glycerol is a biodegradable. the authors summarize the recent developments in homogeneous catalysts and selected organic applications in this area. Palladium along with variety of ligands has been widely employed as homogeneous catalysts to affect carbonylation reactions. Various carbonylation reactions like alkoxycarbonylation. Fourier Transformed Infra-red spectroscopy and electronic spectroscopy. ethyl acetate.or vinylpalladium complex in presence of suitable nucleophiles. and transition metal complexes.N’-bis(salicylidene)-1. which reveals that complex synthetic processes can be accomplished under carbonylation conditions. Chapter 8 – The synthesis.3xylylenediamine] are reported. agrochemicals. Fourier Transformed Infra-red spectroscopy.N’-bis(salicylidene)-1.2-phenylenediamine]. [N. The oxovanadium (IV) complexes were characterized by elemental analysis. thiocarbonylation. the use of glycerol as a solvent promoted improved activities and selectivities of the reactants. can be . in many reactions.x Andrew C. The product of catalytic reaction. benzyl. . and recyclability will be addressed. hydroformylation. improved reaction rates. Nowadays. researchers incessantly invented new and novel phase transfer catalysts with more active-sites and higher efficiency. ultrafiltration or ultracentrifugation. epoxidation. Phase transfer catalysis will be of curiosity to anyone working in academia and industry that needs an up-to-date critical analysis and summary of catalysis research and applications. As a result. Currently. it is now imperative for chemists to invent as many environmentally benign catalytic reactions as possible. lower reaction temperatures and the absence of expensive anhydrous or aprotic solvents. dendrimers will combine the advantages of homo. ultrasound and microwave irradiation assisted PTC transformations have become immensely popular in promoting various organic reactions. it has become an important choice in organic synthesis and is widely applied in the manufacturing processes of specialty chemicals.N’-bis(salicylidene)-1. Catalysis seems to be a research area in which promising applications for dendrimers may be developed. dyes. as biomolecules. and as such they are. or. This chapter highlights some of the notable examples of the catalytic reactions using supported dendritic catalytic systems in such reactions as hydrogenation. In particular. dialkylzinc addition to aldehydes and imines. Some of the prominent features of the PTC include. monomers etc. perfumes. Chapter 9 – The use of soluble supports leads to recyclable catalyst systems that do not suffer from mass transfer limitations. PTC is considered to have great potential for industrial-scale application. Chapter 10 – In view of the increasing environmental and economical concerns.3-xylylenediamine] presents the best catalytic activity in homogeneous system probably due to its flexibility that favors the access of the substrate to active center in the catalysis. This combination of features makes dendrimers suited to close the gap between homo. Cinchona alkaloids and ephedrine derived catalysts are the most popular chiral PTC that has been employed to achieve the goal for inducing asymmetry into product molecules. due to these salient features. selectivity. Further key issues in this chapter relate to the deviating properties of dendrimers as compared to their linear macromolecular counterparts is considered. In view of the success and vitality of this .. additives for lubricants. dendrimers have recently attracted a lot of attention. dendritic catalysts are nanosized. pesticides.and heterogeneous catalysis. but the present chapter is specifically focus on summarizing the major concepts for their properties as well as the most pronounced advances for their applications as supports for recoverable catalysts and reagents in asymmetric synthesis. ingenious new analytical and process experimental techniques viz. The intriguing properties of dendrimers in catalysis including activity. Heck and other Pd-catalyzed C-C bond formation. ‘‘phase transfer catalysis’’ (PTC). Owing to its simplicity and the low cost of most of the phase transfer catalysts. Successful completion of reactions involving lipophilic and hydrophilic reactants can be achieved by employing an environmentally benign technology viz. Indeed. in other words. Asymmetric phase-transfer catalysis has attracted considerable attention as a convenient technique for the synthesis of chiral molecules. Dendrimers have a number of potential applications. the PTC technology has found universal adoption.and heterogeneous catalysis. stability. The oxovanadium (IV) complex from the Schiff base [N. Due to ever increasing necessity of increasing the efficiency of PTC in industries.Preface xi used as an intermediate in the fabrication of pharmaceuticals. filtration. since these well-defined macromolecular structures enable the construction of precisely controlled catalyst structures. and therefore they should lead to systems with activities similar to their monomeric analogues. easily isolable from homogeneous reaction media by precipitation. such as drugs. alkyation. pharmaceuticals. Perfumers [5] define their fragrance a little more precisely: cis-hex-3-en-1-ol is specified by its intense smell of fresh grass.92-2. the authors have proposed to present recent happenings in the field of PTC and to study its applications to various organic reactions. 0. and 0. lavender and brandy mint oil.xii Andrew C.trans-hex-2. These compounds can be prepared by selective hydrogenation of the sorbic alcohol obtained for example from the chemical reduction of sorbic acid. The titling of the two hexenols as leaf alcohols is partly reflective of their smell – their fragrance resembles that of freshly cut grass. it is a component of geraniol. The use of homogeneous catalysts opened new possibilities to carry out the hydrogenations and significantly higher selectivities of formation of the desired products. Typical applications of PTC in silent. it is added to flower aromas (lilac for example) and it can be used in imitations of mint and different fruit mixtures. The effects of the mass ratio of catalyst/SA. As stated above hexenoic acids and alcohols have very interesting fragrant properties. aldehydes and acids are widely used in perfume chemistry. specifically cis-hex-3-en-1-ol and trans-hex-2-en-1-ol. The major disadvantages of the use of heterogeneous catalysts in this case are the low selectivity of the process (in the case of hex-3-enoic acid derivatives there is essentially no selectivity) and the use of sorbic acid itself is impossible. The easiest method for the preparation of hexenoic acids from the point of view of selectivity and simplicity is the selective hydrogenation of easily available sorbic acid (trans.4-dienoic acid).24 without any catalysts.34 with DMAP.31 with NBS.54 under the experimental conditions catalyzed with iodine. Chapter 11 – Some C6 unsaturated alcohols. Details of the preparation of these compounds by hydrogenation using heterogeneous catalysts are given elsewhere [1-4]. and reaction temperature on the degree of substitute (DS) of cellulose were investigated. Further. Instead salts or preferably methyl or ethyl esters are used. kinetics of various organic reactions catalyzed by PTC carried out under a wide range of experimental conditions will be presented. can be obtained in various mixtures. The results showed that the DS of cellulosic derivatives increased to 0. It is also used for a refreshing orange aroma and it is a component of artificial geraniol and lavender oil. The possible mechanism of .94-2. Nbromosuccinimide (NBS). from 0. Poehler technique. The fragrant properties of hexenoic aldehydes are also very interesting for the perfume industry but the simplest method of preparation (aldol condensation) was not superseded by hydrogenation due to the low stability of aldehydes. and 4-dimethylaminopyridine (DMAP) in a solvent system containing 1-butyl-3-methylimidazolium chloride ionic liquid ([C4mim]Cl) and dimethylsulfoxide (DMSO). Chapter 12 – Homogeneous modification of sugarcane bagasse cellulose with succinic anhydride (SA) was catalyzed with three different catalysts including iodine. It is used as an imitation of raspberry or in many other fruit aromas that require a caramel-acid note. it is sweeter and more fruity than cishex-3-en-1-ol and it is often used as a component of artificial strawberry. Depending on the catalyst used different regio and stereoisomers. ultrasonic and microwave conditions are described. transHex-2-en-1-oic acid has a warm fruit aroma after dilution. trans-Hex-2-en-1-ol has in low notes a strong fruit smell (chrysanthemum or wine). From hexenoic alcohols the most commonly used compounds of this type are the socalled “leaf alcohols”. reaction time.56-1. partly herbaceous and slightly acidic. introducing another step to the process. indicating that these three catalysts were effective catalysts for cellulose succinoylation in ionic liquids. Pd. thereby generating an enormous interest in its palladium complexes in recent years. The strong σ-donating nature of the N-heterocyclic carbene ligand in the catalyst allows oxidative insertions of challenging substrates while the ligand topological steric demands promote the fast reductive elimination reactions. the Pd complexes of N-heterocyclic carbenes perform various other reactions like the oxidation reactions. it is possible to accelerate the formation of catalytically active species and prevent or hinder the processes that lead to catalyst deactivation. Additionally. N. O and S) bonds under ambient conditions. the air and moisture stability and the functional group tolerance. . the strong palladium−N-heterocyclic carbene (Pd−NHC) interaction help stabilizes many catalytically important active species at low ligand to Pd ratios and also at high temperatures thereby broadening its scope of catalytic applicability. it is possible to vary the yields of target products. A key strength of Pd mediated synthesis thus lies in its chemo. In this context notable is the contribution of Pd towards the development of the area. Understanding of the mechanisms of the additive’s action at the formation of catalyst active forms and mechanisms of regulation of the elementary stage of the radical-chain oxidation may apparently lead to the development of new. Of late. Cat–ROOH. Cat–RO2 and in that way of controlling the rate and selectivity of processes of radical-chain oxidation [20]. the N-heterocyclic carbenes (NHC) have added a new chapter in the design. Tsuji-Trost reaction and the polymerization reactions etc. Apart from the C−X (X = C and N) bond forming reactions. and C-3 positions in cellulose occurred. The specialty of Pd as a metal lies in its ability to efficiently construct numerous types of C−X (X = C. By introducing various ligands-modifiers into reaction. Chapter 14 – The application of metal-complex catalysis opens the possibility of regulating the relative rates of elementary stages Cat–O2. The results indicated that the reaction of hydroxyl groups at C-6.and regio selectivities that facilitate the synthesis of intricate target molecules otherwise not conveniently accessible by traditional methods. being a late transition metal. Even extending further beyond chemical catalysis. Fourier transform infrared and solid-state crosspolarization/magic angle spinning 13C NMR spectroscopies also provided evidence of catalyzed homogeneous succinoylation reaction. Furthermore. The catalyst performance is always accompanied by its deactivation. inherently possesses important attributes like. and thus control the reaction selectivity. It should be mentioned that in its original form. the palladium N-heterocyclic carbene complexes exhibit promising potential in various biomedical applications like in the anticancer studies. discovery and development of Pd catalysts. By changing the ligand environment of the metal center or adding different activating compounds. Chapter 13 – The knowledge of the efficient formation of C−X (X = C and N) bonds asymmetrically or otherwise is vital to contemporary organic synthesis. efficient catalytic systems and selective oxidation processes. which often are the key ingredients of a successful catalyst. C-2. which together constitute two important steps in numerous catalysis cycles.Preface xiii homogeneous succinoylation catalyzed with these catalysts and the actual role of these catalysts were also investigated. a catalyst often represents only the precursor of real catalytic particles. . trying to obtain materials that can have both properties as large. García-Peña and F. Inc. Cd.In: Homogeneous Catalysts Editor: Andrew C. Since nanoparticles have high relationship superficial area/volume which gave them their different properties compaired from their macromolecular counterpart. Coyoacán. telephone +52-55/5622-8602. usually a polymer matrix. ext. INTRODUCTION Nanocomposites can be defined as nanomaterials that combine one or more separate components in order to obtain the best properties of each component in which nanoparticles act as fillers in a matrix. C. Universitaria A. E-mail: rredon@unam. Chapter 1 METALLIC NANOPARTICLES NANOCOMPOSITES: THEIR CATALYTIC APPLICATIONS Rocío Redón*. Poehler ISBN: 978-1-61122-894-6 © 2011 Nova Science Publishers. 70-186. 04510. F. basically. recoverable and reusable supports but with plenty of reaction centers. N. they are so reactive * Corresponding Author Rocío Redón. in particular. México D. the noble or platinum group metals are the metals commonly used as catalysts although some of the others have been proven to work as catalysts on different reactions. which can be soluble obtaining the benefits of homogeneous catalysts. 1154. Also. ABSTRACT More than a simple review. this is a compilation of what has been done so far in relation to metallic nanoparticle-polymer composites with applications in catalysis reported up to now. FAX +52-55/5622-8651. In catalysis. México.. . P. G. We are going through all the transition metals from scandium to the noble metals to the copper group. while the matrixes are the supports of these centers. metal nanoparticles act as catalysis centers. we report that. like in heterogeneous catalysis.P.mx. Ramírez-Crescencio Centro de Ciencias Aplicadas y Desarrollo Tecnológico Universidad Nacional Autónoma de México. where the authors fount that. the high catalytic activity of SSP-Au/TiO2 1073 is attributed to the highly dispersed gold particles being modified by a strong interaction with TiO2 that induced a synergy effect in the catalysis [1]. Possible interactions in Nanocomposites. can produce metal oxides and usually are employed as supports of other metallic nanoparticles. Intra-molecular interactions (Chemical bond) Sc-Mn groups The first elements that we are going to address. Titanium. A TiOx porous layer obtained by templating synthesis was used as nanostructured reservoir for an organic corrosion inhibitor.2 Rocío Redón. Inter-molecular interactions = Metallic NPs = Matrix molecules Figure 1.or intra-molecular interactions or a combination of both (Figure 1). or the main research is around some optic applications. . finally. thus in this part we are going to mention a few researches. are from the groups scandium to manganese. No information about synthesis of Nb nanocomposites has been found during the present review. where they report spectral features of far-infrared electromagnetic radiation absorption in anatase TiO2 nanopowders that they attribute to absorption by acoustic phonon modes of the dispersed nanoparticles [3]. some others only report the synthesis of the nanocomposites TiO2-metallic NPs [2]. basically for heterogeneous catalysis. N. like in the Murray´s paper. On the other hand. Ramírez-Crescencio that it is necessary to protect them by adding extra molecules such as polymers or dendrimers and they can have either inter. that include the above mentioned metals and their applications. G. This provides active corrosion protection and self-healing ability of the coating system [4]. García-Peña and F. which basically. we have found a example where titanium NPs are use in medical applications where the authors reported a increased skeletal muscle cell and osteoblast numbers on hydrothermally-treated nano-hydroxyapatite/collagen type i composites for entheses applications [5]. it is well known that titanium has been largely used as titanim oxide as catalyst support. and in this direction there are some researches that include gold metallic nanoparticles as catalyst centers. as corrosion protective. B. P.5Cu27.Metallic Nanoparticles Nanocomposites 3 The case of vanadium is similar to titanium.5. no information about synthesis of Niobium nanocomposites has been found during the present review. [20] have prepared an alloy ingot with a composition Zr65Al7. the ability to control the characteristics of the phase transition [7c]. Qiang et. Many of the articles about Zirconium and nanoparticles are more related with ZrO2 (zirconia) as an excellent support of other nanostructures [19]. Although. some investigations about metallic nanostructured zirconium have been informed. the case presented is a metallic Ag arrays assembled in nanoporous VSB-5 nanocrystals. originally accommodated in the mineral. where they demonstrated. which in the case of asymmetric catalysts. Gubin [24] and collaboratores reported a metallic zirconium-poly(carbosilane) nanocomposites. essentialy as Y2O3. S. where the catalytic activity of these Ag(O)-VSB-5 composites was found to be highly efficient catalysts for the syntheses of olefin aldehyde from styrene [6] and in optical applications with vanadium oxide (VO2) in a study where they reported that the optical contrast between the semiconducting and metallic phases is dramatically enhanced in the visible region. As in the case of scandium. on the manufacture of new generation catalysts containing various metals (nickel. al. [21] reported an Cu50Zr50 alloy. or as an etch mask to fabricate pyramidal pits and then as a deposition mask to form the metallic pyramids [9] As in the previous elements. manganese. thus the reports include vanadium composite as catalyst. Other examples of alloys as Dutkiewicz’s [23] can be found. where the optical properties of the nanocomposites demonstrates that the obtained nanocomposites can be used as passive Q switches [8]. Bulk metallic glasses based on zirconium NPs had attracted great attention due to their elastic strain and remarkable plasticity [20]. And the group of Eckert [22] has achieved Zr62-xTixCu20All0Ni8 bulk samples (0 ≤ x ≤ 7. moved to the outer surface. or in a material to build fiber-optic by using ion implantation to dope the VO2 nanoparticles with tungsten or titanium ions. (yttria) [15] and yttrium aluminium [16] (or iron [17]) garnet nanoparticles. palladium) deposited on a porous support such as alumina or silica gel. J. copper. In the case of chromium we only found reports related to optical application with the use of aerosils modified by chromium oxide. presenting size-dependent optical resonances and size-dependent transition temperatures [7a] in a study concerning the absorption and scattering of infrared radiation by vanadium dioxide nanoparticles with a metallic shell. where the catalytic metal cations. where the authors prove that the transition of VO2 to the metallic state near (or away from) plasmon resonances leads to a decrease (or increase) in the absorption and scattering cross sections for a given wavelength [7b]. where they aggregated to metallic nanoparticles available for the growth of the nanotubes [12] and just. at. synthesized for future applications [13]. Pd nanoparticles associated to cinchonidine as an asymmetric ligand inside silica particles have been prepared by this process for the ethyl pyruvate hydrogenation [11]. obtaining a synergistic catalytic effect on conversion and selectivity in the case of Au/MnO2CeO2 catalysts. yttrium has become an important constituent of various materials for technical applications [14] and a wide range of articles have been published. Metallic niobium particles are reported only in . or for the production of carbon nanotubes with marine manganese nodule as a versatile catalyst. manganese also has been used as manganese oxide as support for gold NPs. due to the coexistence of metallic and nonmetallic gold species within nano gold particle and the minor presence of Ce3+ species [10]. In the last years.5).The only example that we found reported related to metallic yttrium involves an Al–Y–Ni–Co–Pd alloy achieved by the group of Louzguine-Luzgin [18]. Hajlaoui et. N.2 nm and show activity on the oxidation of rhodamine. due to their reactivity with environmental oxygen. Mesoporous doped TiO2 nanoparticles have mean diameter of 20 nm with mean pore size of 2. or Petukhov’s [35] are focus on this system. some investigations have been made on Nb as support of magnetic Tb nanoparticles [26]. Prunier’s [34]. using ionic liquids (ILs) as stabilizers [37]. Fortunatelly. Reddy and coworkers [45] have synthesized nanocomposite oxides of CeO2HfO2. Purohit [29] has obtained NPs through microwave assisted electron cyclotron resonance (ECR) plasma induced chemical sputtering process. Díaz et. Berko’s group has achieved Mo nanoparticles on a TiO2 (1 1 0) surface trough molecular vapor deposition (MVD) [30]. al. [50] have obtained Ta2O5/SiO2 particles by flame spray pyrolysis (FSP). This oxide presented a catalytic activity for NOx reduction with methane in the presence of oxygen. where the authors inform that these NPs have compositions based on TcxSy. Silica-Hafnia nanocomposites have been obtained by Loureiro et.nH2O by Meskin et. Tantala-coated polystyrene (PS) particles were prepared by hydrolyzing tantalum ethoxide in ethanol at 28 °C in the presence of functionalized PS beads (540 nm). Only a few reports have ben found related to lanthanum NPs. for soot oxidation. [47] Reactions of hafnium isopropoxide with hafnium halides at high temperature in pure TOPO (Trioctylphosphine oxide) yield nanometer-sized HfO2 nanocrystals of 5. . al. [44] have obtained Lanthane-doped mesoporous TiO2 nanoparticles via hydrothermal process by using cetyltrimethylammonium bromide (CTAB) as surfactant-directing agent and pore-forming agent. Nano-tantalum powders have been prepared by arc-plasma method and the average diameter of the grains is 10 nm [49] the product consist of a large quantity of nanoparticles of tantalum and hexagonal δ–TaO phase. some reviews of 99mTc nanocomposites are reported [38-40]. al. like the one from Cao et. who informed a method for preparing graphitic carbon encapsulated lanthanum NPs. [42] Fokema and Ying [43] have synthesized La2O3 through an aqueous solution of La(NO3)3 added to an aqueous organic base and aged for 12-24 h. hafnium has been studied as de correspondant. Blondeau-Patissier [32]. Technetium. the polymer core was removed either via chemical treatment with toluene or calcination at 650 °C obtaining sub-micrometer hollow spheres of Ta2O5 [54]. al. V. As the rest metals in these grops. little information about synthesis of metallic molybdenum NPs by soft chemical reduction is found. non-aqueous condensation of tantalum ethoxide [52]. Redel’s group had obtained dispersions of this metal through thermal decomposition of Mo(CO)6. like Pétigny ‘s [31]. Physical techniques of synthesis were used when metallic molybdenum NPs were required. Ramírez-Crescencio alloys. Other studies. with particle sizes of 6-7 nm. Molybdenum nanocomposites are more usual than “naked” or not protected NPs. al. L. al. Peng et. 99mTc is widely used in radiopharmaceutical for diagnosis and therapeutic purposes [38] mainly as coordination compounds [39]. lanthanum hydroxide nanofibers have been synthesized by Djerdj et.A.4 Rocío Redón. Unlike physical techniques. On other paper. G. In addition. S. [41]. al. using hydrogen as the ionizing gas. Domenichini’s [33]. as thin films [27] or matrix [28]. García-Peña and F. Schulz et. generally with Fe and B [25]. in this direction B. [46] Nanoparticles of HfO2 have been obtained through ultrasonically assisted hydrothermal decomposition of HfO(OH)2.5 nm [48]. oxides of tantalum have been synthesized by thin-wire explosion [51]. On other investigations. and hydrolysis of tantalum ethoxide [53]. [36] have obtained alumina/molybdenum nanocomposites putting together α-alumina powder and MoCl5 in anhydrous ethanol. Mo. 10 nm crystallites of elemental tungsten were obtained [57]. thus we are going to mention some of the last papers related on nanocomposites that contain iron nanoparticles and their uses mainly on catalysis. especially in within the employment of nanoparticles. BMim+OTfand BtMA+Tf2N. even though there are some other applications like in magnetism or optical. Rhenium nanostructures have been synthesized by Hassel and coworkers [62].(BMim+ = n-butyl-methyl-imidazolium.%Re eutectic alloy was directionally solidified using a constant growth rate and temperature gradient. A NiAl– 1. [63]. rhenium sulfide nanoparticles have been obtained by Tu et. iron has become more important in catalysis. Tungsten NPs [56] are obtained reproducibly by thermal or photolytic decomposition under argon from mononuclear metal carbonyl precursors M(CO)6 (M = Cr. al. A mixture of scheelite (CaWO4) and magnesium was milled together for 100 h in a nitrogen atmosphere. on the other hand. Finally. OTf = O3SCF3) with a very small and uniform size of 1 to 1. al.which increases with the molecular volume of the ionic liquid anion to ~100 nm in BtMA+Tf2N-. On the other hand. WO3/polyacrylonitrile nanocomposite were obtained by Wei et. Thermal plasma process was applied by Ryu et. which will be mention also. [58] to produce nanosized tungsten powder using ammonium paratungstate (APT) as the precursor. Makaryan [61] have studied the synthesis of composite polymer-based materials. nanosized W powder consisting of spherical particles of less than 50 nm was obtained. using a Fe-0/Fe3O4 composite [65]. Additionally WO3/TiO2 has been successfully tested for selective catalytic reduction of NOx. produced mainly long rhenium fibres.Metallic Nanoparticles Nanocomposites 5 Sahoo and coworkers [55] have obtained tungsten nanoparticles by thermal decomposition of tungsten hexacarbonyl [W(CO)6] at 160 °C in presence of a mixture of (1:1) surfactants. with good results. [60] stirring WO3 nanoparticles in a commercially available polyacrylonitrile (PAN) solution. in the decomposition reaction of H2O2 by measuring the formation of gaseous O-2. Fe/SBA-15/carbon composites were used as . oleic acid and trioctyl phosphine oxide (TOPO) under a blanket of Ar gas. The presence of surfactant reduces the particle size and with further increase in surfactant concentration increases the particle size. In the last years. al. FE-CU GROUPS These are the main metals that had ben involved in catalysis since the catalysis was explored. BtMA+ = n-butyl-trimethylammonium. after removal subproducts. Tf2N = N(O2SCF3)2. WO3/TiO2 composite NPs have been synthesized by dissolving W and Ti precursors in a suitable solvent and spraying into a high temperature acetylene-oxygen flame using a reactive atomizing gas.5 at.For example they had been used supported on carbon nanotubes in during FisherTropsch synthesis [64].5 nm in BMim+BF4. The selective dissolution of the NiAl matrix with a mixture of HCl:H2O2 produced rhenium fibers (diameter ~400 nm) Digestion of the NiAl–Re eutectic in sulphuric acid. [59]. thus we are going to try to cover the newest publications on the nanocomposites metal NPs-support molecule and their catalytic applications. Results indicate a higher hardness using amorphous nanosized tungsten fillers with a particle size less than 10 nm. The produced tungsten powder was treated by hydrogen during which minor amounts of WO2 or WO3 were reduced to tungsten. W) suspended in the ionic liquids BMim+BF4-. Polymeric matrices chosen are the copolymer of formaldehyde and dioxalane (CFD) and the polyphenylene sulphide (PPS). obtaining sizes from 5 to 20 nm and 10 to 50 nm. The Fe the active state of the catalyst is a crystalline metallic nanoparticle. The rest of the papers that we have found are related to other applications such as optical [128-124]. there are also some papers related to magnetic applications [104-107] and those dedicated on the nickel nanocomposite synthesis [108-113]. Ramírez-Crescencio catalyst in the benzylation reaction of benzene with benzyl chloride [66]. such is the case of the reactions to produce Hydrogen by reforming of methanol in supercritical water. as cathode material [127]. where the authors propose that the iron species dispersed in clay matrix may provide the catalytic active sites and the size of iron species has an effect on selectivity [68]. on other paper. where the nanoparticles were more efficient without the support [102]. in their use as catalysts in Sonogashira coupling reactions [101]. The as prepared copper NPs are catalytically active toward the mentioned "Ullmann reaction"-that is. dissecants. in order to understand the oxidation of the nanoparticles surface when catalytic reactions take place and to understand more of the enantioselective heterogeneous catalysis. Most of the reports are related with the magnetic [71-82]. optical properties [83]. to obtain a catalytic conversion of phenol oxidation of 49. as support like iron oxide with gold NPs in methanol oxidation. in microwave oxidation of alcohols using supported metallic iron nanoparticles [70]. as model catalyst Fe film on SiO2 during preannealing in O-2 and NH3 and during C2H2 decomposition. The reports that we have found for cobalt nanocomposites are some related to magnetic applications [97-99] and one more related to the synthesis for future applications [100]. in this paper the authors reported the in sittu generation and regeneration of the Cu NPs catalyst [114].4 % of selectivity to carbon dioxide and tar. The case of nickel. in methanation. the authors reported that copper metallic particles are formed and get anchored in the siloxane oligorner obtained during the reaction of phenylsilane and ethyleneglycol with bispyridinium. in the synthesis of carbon nanotubes (CNT). in the design of permeable reactive barriers [85]. in the Ullman reaction with sonochemically derived copper powder that shows the presence of porous aggregates (50-70 nm) which contain an irregular network of small nanoparticles. the use of copper NPs. studing their mechanical properties [128]. . yielding nanofiber-supported iron oxide nanoparticles. the condensation of aryl halides to an extent of 80-90 % conversion [115]. the authors made a study with nickel NPs and tartaric acid [103]. where the best performance was obtained when the catalyst was calcined at 500 °C and reduced at 550 °C [117]. obtaining an enhanced oxidation with the use of this support [69]. while secondary carbon nanofibers with diameters in the range from 10 to 20 nm were subsequently grown from cyclohexane catalyzed by the sintered metallic iron nanoparticles under reducing conditions [67d]. as templates [84]. as humidity sensors [86] or only the synthesis of iron nanocomposites for future applications [87-96]. García-Peña and F. in the case of metallic iron particles in montmorillonite matrix. in this case deposited onto mesoporous SBA-15 support were proved in catalytic activity tests for CO oxidation. where the catalyst metal surface supplies sites to dissociate the hydrocarbon precursor and then guides the formation of a carbon lattice and the liftoff of a carbon cap. while graphitic networks do not form on oxidized Fe [67a]. by using a nanocomposite of montmorillonite clay through anchoring on FeCo nanoparticles [67b] or by using Fe-doped carbon aerogels [67c]. as combustion characteristics [125]. as in its bulk applications.5 % with a 67. There are some papers dedicated to copper NPs catalysis. tetrachlorocopper(II). G. N. These supported metallic copper particles can catalyse the coupling reactions of silanes with alcohols [116]. by employing ferrocene. there are more catalysis examples. as insulators [126]. Finally.6 Rocío Redón. and there are those related to the synthesis of copper nanocomposites [129-133]. with silica supported Ni NPs. In the last case. Quantitative conversion was achieved in 25 minutes when 5 nm particles are used. they have explored the synthesis of this catalysis via polyol method assisted by microwave irradiation [136].7 h-1. Quantitative conversions were achieved in almost every case with TOF up to 74900 h-1. the best result was achieved with 81. Metallic ruthenium NPs are used in the catalytic hydrogenation of unsatured bonds. al. and 9.3-butadiene in the gas phase [137]. and templated mesoporous carbon supported ruthenium(0) nanoparticles [140]. the same catalyst was reported as the most catalytically active. in 1. and a selectivity of 83% to cyclohexanone product (cyclohexanol is the only byproduct). tested γ-Al2O3 supported metallic ruthenium nanoparticles in the catalytic hydrogenation of methyl benzoate to methyl cyclohexanoate. In contrast. Raspolli Galletti et. Quantitative conversion is achieved when the ruthenium composite is used.3-dioxane to 2-(4-carbomethoxycyclohexyl)-1. though they found less selectivity of the desired product (95%). and finally test it in the catalytic hydrogenation of benzene [139]. using tetrahydrofuran (THF) as solvent. which has shown a catalytic activity up to 88% conversion in 2 h. better results were obtained in comparison with other catalysts (Ru/C and Ru/Al2O3) prepared by the authors. A Ru/silica catalyst was tested too in the hydrogenation of benzene under biphasic (ionic liquids-benzene) conditions.Metallic Nanoparticles Nanocomposites 7 Ruthenium catalysis. Boujday and collaborators have used a SBA-15-type mesoporous silica to introduce the [⎨Ru-(C6Me6)⎬2Mo5O18 ⎨Ru(C6Me6)(H2O)⎬] poly-oxomolybdate by wetness impregnation.1.5% selectivity for the citronellal (CIAL) product. almost quantitative conversions were achieved in almost every experiment with TOF up to 37. Chaudret group obtained ruthenium nanoparticles supported onto nanoporous alumina membranes.5 h. reduce under a reducing atmosphere. and. Su and collaborators have synthesized silica. have developed γ-Al2O3 supported ruthenium(0) NPs to catalyze the hydrogenation of phenol [135]. These NPs were tested in the reduction of citral. and 2-(4carbomethoxyphenyl)-1. and lower times of reaction (15 h) were achieved. In a previous work.3-dioxane [134]. nerol. with better catalytic activity at 623 K. carbon coated silica. the authors performed a modified catalytic test in solventless conditions. When these catalysts were tested in the hydrogenation of benzene and toluene. Kantam and coworkers obtained nano-crystalline magnesium oxide supported ruthenium nanoparticles. the best results were found for the Ru-TOA supported on γ-Al2O3 using cyclohexane as solvent. citronellal and citronellol. they have determined better activities for the nanoparticles pre-reduced and later supported due to regularity inside the pores. In a similar synthesis. In this case. . al. Marconi et.5% conversion in 2 h. In the hydrogenation of benzene. for the hydrogenation of citral when two montmorillonite supported ruthenium catalysts were used [142]. Recently. as principal products).8 h-1 for toluene. Manikandan and co-workers obtained less selectivity and a major dispersion of products. when the silica modified PVP support is used. Liu’s group has used the 1. For methyl benzoate. with 87% selectivity to cyclohexanone product. and a TOF of 667 h-1. Quantitative yields were reported at 40º C. with 75.3-tetramethylguanidinium trifluoroacetate ([TMG][TFA]) ionic liquid to support metallic ruthenium nanoparticles on montmorillonite (MMT) [143]. Recently. for benzene. in the case of 2-(4carbomethoxyphenyl)-1.3-dioxane. using dichloromethane as solvent. from 11% to 43% (geraniol. Han’s group used a PVP (poly (vynilpyrrolidone)) modified silica to support ruthenium nanoparticles [138]. and tested them in the catalytic hydrogenation of 1. with a quantitative reaction in 20 h. with a quantitative reaction in 8 h. The Tsang’s group used CO2 supercritical microemulsions to synthesize Ru nanoparticles [141].3. thought better selectivity is achieved with the correspondent α-cyclodextrin with o-xylene.8 Rocío Redón. Asedegbega-Nieto and co-workers have supported ruthenium nanoparticles onto carbon nanofibers with different topographies and used them to hydrogenate selectively 4-acetamidophenol (paracetamol) [145]. and applied these catalysts in the hydrogenation of toluene [147]. These catalysts were compared with their sulfide analogous. In a recent investigation. at 110º C. if the metylatedβ-cyclodextrin is used as stabilizer. is Denicourt-Nowicki et.1’-bi-2naphtol (ee of >99.6’. the best trans-/cis. N.m. By their way Zhao’s group.Ndimethyl. The best TOF (83. yet better selectivity toward the formation of isomerisation products. which were used in the catalytic hydrogenation of arenes [150].7’. the authors determined that the best support is the platelet-type carbon nanofiber with a quantitative conversion of toluene to methylcyclohexane with a TOF up to 14200 h-1.5’. In every case. In a previous work. 95% conversion of acetophenone to 1-phenylethanol (acetone as by product) was achieved in 6 h. The best results were for cyclohexene with a TOF of 34 h-1.9%). this group developed the stabilization of Ru(0) NPs by the random methyladed cyclodextins [151]. Almost quantitative conversion (99. The best results were achieved for BINOL with a substrate/catalyst ratio of 1390.3-dimethylcyclohexane. the reduction of aryl group is achieved. Takasaki and collaborators used carbon nanofibers to support ruthenium nanoparticles and used them in the partial hydrogenation of 1. the catalysts were tested in the catalytic hydrogenation of o. with superior results for benzene with 25h-1 TOF. with 30. [149]. In the same line of investigation. In other work. the main product was a mixture of cis. On the other hand.3 h-1) was achieved for the hydrogenation of styrene. the reaction was quantitative. García-Peña and F. at 50º C.1’-bi-2-naphthol (BINOL) derivatives [146]. When longer times are used in the catalytic reaction. and the authors reported lower catalytic properties. There. Superior results were obtained when randomly 3methyladed-β-cyclodextrin is used as stabilizer in the catalytic hydrogenation of m-xylene.6% selectivity for the cis-1. During the catalytic hydrogentation.8’-octahydro-1. Ramírez-Crescencio using chlorine hydroxide ionic liquid. the same group combined randomly methylated cyclodextrins and N.and p-xylene. this group used carbon nanofibers with different topographies as supports. when β-cyclodextrin is used as part of the inclusion complex. al. and realized the first attempts to apply these ruthenium NPs in the catalytic hydrogenation of aryl derivatives [152]. and in every case.7.and trans-4-acetamidocyclohexanol with conversion of 60%. Philippot. LZY-82 and a dealuminated DLZY-82) to prepare zeolite supported ruthenium NPs by ion exchange and subsequent reduction in a H2 flow [153].0 h. Other group that has used carbon to obtain a Ru(0) catalyst. and used them in the transfer hydrogenation of various carbonyl compounds [144].8%) is achieved when a benzene/Ru(0) ratio of 10000 is used. In this investigation.N-(2-hydroxyethyl)-ammonium chloride salt to form an inclusion complex and stabilize metallic ruthenium nanoparticles. Roucoux and Claver’s group have developed an interesting oncoming to enantioselective . employed templated porous carbon materials to obtain supported ruthenium nanoparticles.8. when 3-methyladed-βcyclodextrin is employed.6. A previous work from this group focused in the stabilization efficiency of the methylated cyclodextrins. quantitative reactions were achieved in different times. and a TOF of 9980 h-1. al have used a series of Y zeolites (PQ-13. and used them to catalyze the hydrogenation of benzene [148]. in 48 h. and 88.6.5 h-1 TOF.4) is achieved when the ruthenium nanoparticles are supported onto the platelet-like carbon nanofiber.N-hexadecyl. Sun et. with a 99% yield of isolated 5. in 1. G. though only the alkene is reduced. the catalysts were tested in the catalytic hydrogenation of alkenes.ratio (1. These stabilized NPs were used in the catalytic hydrogenation of arenes in biphasic conditions. al. when the hydrogenation of more substituted benzenes are carried out. In contrast.Metallic Nanoparticles Nanocomposites 9 catalysis [154]. poor results are obtained when the catalyst is employed in the reduction of aryl derivatives (3. On the contrary. better result is achieved for the hydrogenation of α-acetoamido acrylic acid with a quantitative conversion to N-acetylalanine. the hydrogenation of carbon monoxide to yield hydrocarbons (Fischer-Tropsch process) was reported by Kou and Yan’s group [158]. low conversions are achieved.6 h-1 has been achieved for the reaction carried out in water. they have used furanose derived diphosphite ligands as stabilizers. The obtained NPs get poor TOFs (from 0 to 6 h-1) for the reduction of phenylaldehydes. quantitative hydrogenation was achieved in pentane. When the Ru/SnO2 and Ru/PVP were tested for . with a TON of 98. with superior TOFs from 1.3 h-1 TOF for p-aminomethyl-benzoic acid to 4-aminomethylcyclohexane carboxylic acid with 3 cis-/trans. to 45. Zuo group prepared SnO2 supported metallic ruthenium NPs and used them to catalyze the hydrogenation of o-chloronitrobenzene [163]. used RuO2 as precursor to synthesize Ru(0) nanoparticles in ionic liquids [156]. al. for benzene. with 60% selectivity for C10-C20 hydrocarbons. Dupont’s group has achieved metallic NPs in ionic liquids. with a quantitative conversion and a TOF of 953 h-1. achieved PVP protected nanoparticles and used them in the catalytic hydrogenation of arenes. A lower. using NaBH4 as reducing agent. A more recent investigation is reported by Kang et.7 h-1 TOF. olefins and carbonyl compounds [157]. They have used supported ruthenium nanoparticles onto different supports to carry out the Fischer-Tropsch process [159].6 h-1 TOFs were achieved for the hydrogenation of ethyl pyruvate to ethyl lactate in a homogeneous medium (ethanol).methylanisol. so the cataytic tests can be carried out in biphasic or homogeneous mediums. Other colloidal ruthenium NPs were achieved by stabilization with octa(aminophenyl) silsesquioxane (OAPS). where an activity up to 1. The catalyst was tested in the catalytic hydrogenation of oand m. but still good. at 20º C. 79% selectivity for selectivity for the cis-1-methoxy-3-methylcyclohexane product. By their way. Other catalytic reduction carried out by Ru(0) NPs is the hydrogenation of aromatic nitrocompounds. with a TON of 98. Finally. and in the second case. The best conversion (34%) of CO is achieved for the modified carbon nanotubes supported ruthenium NPs. with 100% selectivity for the cis-1-methoxy-2-methylcyclohexane product. In a homogeneous catalysts approach. Recently. When the catalysts were tested in the reduction of olefins. Yang and collaborators carried out the investigation [160]. When it comes to colloidal nanoparticles. for methylbenzoate.000h -1. in the first case. When tested in the hydrogenation of ketones. Rossi et.ratio). The authors said that their catalyst is soluble in organic mediums. al. Lu et. with a 85% of conversion to methylcyclohexane in 18 h at 75º C. with 16. In the same way. they have used 1-n-butyl-3-methylimidazolium (BMI) and 1-n-decyl-3-methylimidazolium (DMI) N-bis(trifluoromethanesulfonyl)imidates (NTf2) an tetraflouroborates (BF4) ionic liquids to synthesize well dispersed metallic ruthenium nanoparticles by [Ru(COD)(2-methylallyl)2] decomposition under H2 flow at 50º C [155].100 h-1. Pietrowski an collaborators. Quantitative conversions were achieved in every case. and superior result were obtained for toluene when [BMI][BF4] is used as stabilizer. good results with 16. at 20º C. in a biphasic medium (catalyst/H2O). Pertici’s group have used inorganic polyorganophosphazenes to support Ru(0) NPs and used them in the hydrogenation of various unsatured groups [161]. who studied the reduction of o-chloronitrobenzene to o-chloroaniline using magnesium fluoride supported ruthenium NPs as catalyst [162]. quantitative conversion was fulfilled in pentane. TOF is achieved for toluene with 556 h-1 in the same conditions. respectively) [165]. In an article. respectively. using supported ruthenium NPs. In a process contrary to the hydrogenation of unsatured bonds. via a wet air oxidation. the highest selectivity is achieved with 81% and 82% for CO and H2. CNT. activated carbon. with high mineralization yields. The supports used were ZrO2 modified with SiO2. this group supported ruthenium NPs onto CNT through the same method and modified with KOH [166].10 Rocío Redón. At 650º C. Besides. mesoporous high surface area graphite (HSAG). with 95.6% selectivity to CO and H2. a complete decomposition of NH3 is achieved. In other experiment. In a comparative conversion of the arenes to CO2. up to 269 h-1 and 1232 h-1 TOFs were achieved. each. The maximum conversion of methane (65. Concluding that higher temperatures. similar values were reported: quantitative conversion with >99. and 72. G. and Al2O3) were employed to compare the catalytic activities. proving chloride poisoning in the samples.8% selectivity to CO and H2. [169] The catalyst was obtained through a polyol process in presence of γ-Al2O3. ZrO2. synthesized by the same method.2%) was achieved at 673 K. With their catalysts. The best result is achieved at 650º C with a 79% conversion of the methane. The ruthenium NPs were loaded by impregnation of the supports with an excess of solvent (THF and ethanol) volume in a rotatory evaporator with solutions of the precursors. the oxidation is realized in absence of catalyst. are necessary for a good production of CO/H2(syngas). to study kinetically the catalytic decomposition of NH3 [164]. The catalyst used is the same. N. A quantitative conversion was achieved at 550º C. Guerrero-Ruiz and collaborators report this process [172]. this group investigated the partial reduction of methane. with a H2 formation rate of 33. .1% and 67. using the ZrO2-KOH supported ruthenium chlorine free NPs. The ruthenium NPs were supported by incipient wetness impregnation of the support materials using ethanolic [Ru(acac)3] solution.9% selectivity for the desired product. ultrasound is used instead of microwave irradiation. on the formation of completely oxidized products and CO/H2 production [170]. By their way. respectively. In other work. when the reaction is carried out at 800º C. for aniline and phenol. García-Peña and F. and consequently production of Ru(0). al. Other process catalyzed by ruthenium NPs is the oxidation of arenes.5 mmol/(g-catal min). In a previous work. Yin et. other supports (MgO. One of most reported processes is the partial oxidation methane. but in this occasion. the group studied the dependence of the formation of equilibrium RuO2 ⇔ Ru at lower and higher temperatures. Latter. The catalysts obtained via RuCl3 showed poor activities. for aniline and phenol.4%) is achieved with a Ru loading ratio of 14 %. and reduced under a H2 flow. Ramírez-Crescencio the catalytic hydrogenation. they have synthesized a series of ZrO2 materials modified with KOH and NH4-OH (labeled as ZrO2-KOH and ZrO2-NH4OH. at 823 K. respectively. dried. Some examples catalyzed by ruthenium NPs are found.5% conversion of methane. and commercial activated carbon (AC).5% and 95. with up to 88. Gedanken’s group studied the catalytic activity of SBA-15supported ruthenium NPs in the partial oxidation of methane [167]. at 750º C with 83. using NO as oxygen source [171].5% selectivity for the CO product. Zheng and collaborators prepared a series of γ-Al2O3 supported Ru(0) NPs. When the supported catalysts were tested. al. have realized studies in the catalytic decomposition of ammonia. Other work focused in this catalytic reaction is the one developed by Balint et. this group used a similar process to synthesize a Ru/TiO2 mesoporous catalyst [168]. the ruthenium NPs catalyzes the oxidation of molecules also. Better results were achieved in this experiment. Other catalytic reaction that can be seen as reduction is the catalytic ammonia decomposition. The best conversion (58. 473 K is required to obtain 90% and 100%. respectively. while the cesium promoted catalyst is more active at lower temperatures. up to 90% yield was obtained for the trans-γ-lactam.Metallic Nanoparticles Nanocomposites 11 when activated carbon is used in both cases. supported ruthenium nanoparticles over mesoporous TiO2 (modified with dodecylamine) and ZrO2 (modified with sodium dodecyl-sulfate) with high surface area. When different αdiazoacetamides are tested in the intramolecular carbenoid C-H insertion. with a 98% yield of isolated product. In the article. up to initial rate of 19. to also synthesize ammonia [176]. This group. N-p-chlorobenzylN-tert-butyl-α-ethoxycarbonyl-α-diazoacetamide gave the best result. Matveeva’s group developed a ruthenium catalyst for this process [174]. finally. with no [1. prepared by a sonochemical method. Other process reported for the ruthenium NPs mediated catalysis. too: when used the diazoacetamide prepared from L-phenylalanine. Superior activities were achieved for the cesium promoted catalyst in comparison with the ruthenium catalyst.ratio. In the same line of investigation. with more than 160 x 104 TOF.6% selectivity for the D-gluconic acid product. The intramolecular carbenoid N-H insertion reaction catalyzed by NCPS-Ru was examined also: allyl diazoacetates gave proline products with high cis.selectivity and in superior yields (91-96%).0 mol-acid/(h*mol-cat) when Ru/ZrO2 is employed.9 s-1 TOF is achieved with this catalyst. al. synthesis of ammonia is carried out by ruthenium NPs. with up to 91% yield for styrene. with Ru/TiO2. Recently. reported a series of polymer supported ruthenium NPs to catalyze carbenoid transfer reactions [180]. an investigation of catalytic decomposition of NaBH4 to produce H2 via polystyrene microspheres supported ruthenium NPs is reported by Chen and co-workers [177]. in 1 h. Up to 7. When the catalytic oxidation of acetic acid was carried out. With 1 wt. In the catalytic intermolecular carbenoid N-H insertion high yields (99%-60%) were obtained by . The authors report the catalytic production of γ-lactams by the catalytic carbenoir C-H insertion of diazoacetamides derived from amino acids. when Ru/TiO2 is used. Moroz group used the cesium promoted ruthenium catalyst.8x10-3 s-1 TOFs are found for this catalyst. Choi et. up to 95% yields were achieved. too: production of cyclopropyl lactones in good yields (70%-89%) was achieved. The highest activity is reported for the double promoted catalyst. when the NCPS-Ru catalyst was used. which were further oxidized. rapidly disappeared to yield p-hydroxybenzoic and p-hydroxybenzaldehyde acids. in the case of oxidation of succinic acid. % Ru/LiCoO2 loading. modified with the polyol process. up to initial rate of 30 mol-acid/(h*mol-cat). By their way. al. when p-coumaric acid oxidation was tested. with 99. have used two ruthenium alkali promoted catalysts supported onto Mg-Al hydrotalcite (HT) [175]. supported onto MgO. is the oxidation of D-glucose to D-gluconic acid. Seetharamulu et. This catalyst is active toward the intermolecular cyclopropanation of alkenes. using NCPS-Ru as catalyst. These substrates were tested in the catalytic cyclopropanation. Liu and collaborators had used a LiCoO2 supported ruthenium catalyst via a microwaveassisted polyol process [178]. When tested the catalytic intramolecular tandem ammonium ylide/[2.2]rearrangement product detected. the authors try to explain these results.3]sigmatropic rearrangement reaction. Besides the decomposition of ammonia. The catalyst was deposited via two successive wetness impregnation methods of acetone Ru(OH)Cl3 and ethanol Cs3CO3 solutions. rate up to 0. with an exclusive production of the cis-β-lactam. Özkar group have prepared a Ru(0) dispersion stabilized by sodium acetate by chemical reduction with NaBH4 [179]. with 70:30 trans-/cis.05 L(H2)/(s g(catalyst)) achieved. Recently. Perkas and co-workers developed a similar method [173]. Up to 13. The catalysts were prepared by impregnation of Ru(OH)Cl3 into a hypercrosslinked polystyrene (HPS) matrix. Selective aerobic epoxidation of alkenes is catalyzed by ruthenium NPs stabilized by H5PV2Mo10O40 (POM) and supported by wet impregnation on α-Al2O3. using iodobenzene and styrene. when styrene is used. When the catalyst obtained was tested in the Heck olefination. and phenol.2-dimethylcyclohexane.3dimethylcyclohexane. Ikeda and co-workers have achieved a Rh(0) carbon core-shell nanostructure [189]. respectively. Son’s group has achieved charcoal supported Rh(0) NPs with well defined shapes [190]. when the catalytic oxidative cleavage of alkenes is carried out. the synthesis of an other Rh(0) catalyst containing a mesoporous siliceous material. and tetralin with a Rh(0) catalyst [184]. Finally. o-. García-Peña and F. too. Chang group used a series of colloids to catalyze a Heck type olefination and a Suzuki coupling [183]. Besides. and the best results were obtained for anisole and phenol (with 129 h-1TOFs) and styrene (127 h-1 TOF). Different alkenes were tested in the catalytic epoxidation. and the best result was achieved when cyclododecene was used. respectively. [186] During the catalytic tests. with MCM41 pore architecture. and up to 97% for bycyclohexane. Barthe’s group has carried out catalytic hydrogenations in toluene. They carry out experiments in cyclohexene and benzene obtaining >99% conversion under all conditions and TOFs up to 7600 h-1 with cyclohexene. up to 99% isolated yield.4dimethylcyclohexane (with a cis. anisole and o-xilene. up to 62% yield for only one product is achieved. 1. G. obtaining 100% conversion for toluene and anisole. with a 66% epoxide yield.and p-xylene. The worst result was for Aniline (31 h-1 TOF). m-xylene. N. anisole. up to 92% yield is obtained for the 1-methyl-1phenylethene (obtaining methylphenone). By far. Other silica-supported Rh(0) NPs have been achieved by Mévellec et.2dimethylcyclohexane. the most common reaction catalyzed by metallic rhodium nanoparticles is the hydrogenation of unsaturated bonds. they use a series of activated aryl rings. and 94% with a TOF of 120 h-1 for o-xilene. at 353 K. Other hydrogenations catalysis have been carried out over benzoic acid. The best activities are reported for . 1. Finally. 98% for 3hydroxypiperidine. Rossi’s group has achieved recoverable catalyst by synthesizing Rh(0) NPs deposited over an amino modified silica-coated Fe3O4 system [188]. changed a series of variables and determined the best conditions.preference in every case) and cyclohexanol/cyclohexanone. A complete conversion has been reached in all cases under H2 1MPa in less than 3 h. intermolecular carbenoid C-H insertions were tried: the reaction of methyl phenyl diazoacetate with different substrates. Rhodium catalysis. they found and interesting cis-/trans. When a commercial available Ru/Al2O3 catalyst was tested for the Heck type and Suzuki catalysis.12 Rocío Redón. Carbon supported Rh(0) NPs are also used as catalyst for aryl hydrogenation. even better results were found. with 282 h-1 and 300 h-1 TOFS. obtaining ethylcyclohexane. has been reported by the same group [185]. No other products beside epoxide were detected. Ramírez-Crescencio a one-pot reaction of the appropriate amine and ethyl diazoacetate. t-butylbenzene was employed as model reaction obtaining 99% yield in 2 h. Launay’s group have carried out catalytic test over styrene. The best results are obtained for ethylbenzene from styrene and methoxycyclohexane from anisole with almost 100% yields. Previously. toluene. al. 1. On the reduction of aromatic rings. This catalyst was tested with other substrates. The authors. The resulting supported NPs have been used in the reduction of styrene.92/8 ratio of the product 1. with 85% yield for cyclohexanecarboxylic acid. even in scaling up reactions. using silica supported metallic Rh(0) NPs [187]. Yu and Che group used ruthenium NPs supported on hydroxyapatite to catalyze cis-hydroxilation and oxidative cleavage of alkenes [182]. 3hydrooxypyridine and byphenyl. this investigation was developed by Neuman’s group [181]. and up to 85% yield for styrene glycol was obtained. m. the same catalyst has been used in the hydrogenation of methylbenzoate and cinnamaldehyde.-naphthyl)-3-buten-2-one and 2acetyl-5. each. 80% and 100% selectivity for the α.β-unsatured bond or the aryl system have been obtained. In the hydrogenation case. Other aryl derivatives have been used to test the catalytical activity. In other work. In a previous work from the same group. CNT are widely used in the production of metallic NPs. toluene.3. In other investigation.8octahydroanthracene. and methyl benzoate. When toluene was used for catalytic test.1 h-1 TOF has been achieved. dos Santos and Dupont´s group has combined IL (1-n-butyl-3 methylimidazolium tetrafluoroborate) and sol-gel method to immobilize Rh(0) NPs within a silica network [200]. when it comes to phenol. al.8-dimethoxy-3. Other arenes have been used in hydrogenation with these NPs. Wai’s group has reported an investigation in the synthesis of a series of multiwalled carbon nanotubes (MWCNT) supported nanoparticles [191]. synthesized by Cimpeanu exploits the generation and .4% selectivity for 1. ethyl pyruvate and ethyl 3-methyl-2-oxobutyrate in the presence of quinine (QN) and cinchonidine (CD). By their side. 100% and 86% selectivity.2.4.7.4-tetrahydroanthracene. respectively. They have achieved nearly quantitative reactions in every case and TOFs up to 1700h-1. The systems have shown 53% enantiomeric excess (ee) for the α-hydroxiester with 56% yield in 2h and 59% ee with 100% yield. al. have used MWCNT as support materials for Rh(0) prepared by a simple microwave treatment [193]. They have obtained TOFs up to 54 min-1 in 22 min for 1-Decene. These NPs have been used in the hydrogenation of naphthalene and phenol in supercritical CO2.4-dihydronaphthalene have been performed with a modified supported Rh-trioctylamine (TOA). Recently. Kakade et.5.2% conversion has been found with a 62. One of them refers to a system of metallic Rh obtained via water-in-hexane microemulsion method and then supported over carboxylic acid functionalized nanotubes. with up to 99. 118. In a previous article. have been achieved. TON up to 9900 with nearly 100% conversion to methyl cyclohexane has been fulfilled. Other catalyst. Among the nanostructured carbon supports. respectively. respectively. The reactions were carried out at room temperature and 75ºC in n-hexane and solventless. In the first case. Recently. to the hydrogenation of the α.β-unsatured bond have been achieved (not the carbonyl or the aromatic fragments). Park et. Benzene was used as model reaction catalysis. a quantitative reaction and 100% selectivity for the (Z)1-(Dimethylphenylsilyl)-2-formyl-1-hexene product have been accomplished.3. TOFs of 600 h-1 have been achieved for benzene. performed hydrogenations over anisole and benzene with a rhodium in aluminum oxyhydroxide [Rh/AlO(OH)] prepared through a sol-gel reduction [198]. tetralin with a >96% yield has been achieved. >92% of conversion to cyclohexanone and cyclohexane with a ratio 15:1. Other γ-Al2O3 supported Rh(0) NPs obtained by Metal Vapor Synthesis have been used to hydrogenate unsatured bonds by Petrici’s [196] and Vitulli’s group [197]. On the other hand.6. a Rh/Al2O3 catalyst synthetized by flame spray have been accomplished by Hoxha et. The same systems in solventless conditions achieved 1000 h-1 and 5000 h-1. The hydrogenation of 4-(6’-methoxy-2. The hydrogenation of a couple of α-ketoesters. and used in enantioselective hydrogenations tests [195].3% selectivity for 1. In the silylformylation case. have been fulfilled. and silylformylation of 1-hexyne. where 76. al. Wai’s group has obtained Rh(0) NPs synthesized in a water-in-CO2 microemulsion in presence of surfactants [194]. calculated from the NMR peaks intensities.Metallic Nanoparticles Nanocomposites 13 tetrahedral nanoparticles over anthracene.2. this group used the same catalyst to hydrogenate anthracene [192]. respectively. the actual catalyst was entrapped in a bohemite matrix by gelation with water [199]. Dyson’s group combined the PVP-Ionic liquid method to synthesize a catalyst highly active under biphasic hydrogenation of unsatured molecules [205]. TOF values for both hydrogenations have been found in the order of 104 h-1 and 102 h-1.3’-bipyridine and 4.4’-bipyridine in all cases. phenylacetylene and styrene kinetic tests were carried out also with this system. Other work from this group reports the synthesis of the same system with 2. using PVP entrapped Rh(0) NPs reduced by Cp2V. Delmas et. Diferent bipyridine ligands were used alongside ionic liquids to obtain colloidal Rhodium NPs and later used in aromatic hydrogenation. BMim+OTf. to study the catalytic hydrogenation of oct-1-ene in a biphasic system [210]. reported poor conversions in many hours due to aggregations and lost of catalytic activities of the Rh(0) NPs. cumene. Nearly quantitative conversions for styrene. toluene. The best results were achieved for 4. In a previous article. Recently. PVP is other capping agent used in the stabilization of colloidal NPs.2’-bipyridine ligand and their use in hydrogenation of styrene under different conditions [209]. al. cyclopentene. have used PVP protected rhodium NPs. 250 h-1 TOF is achieved. benzene. Janiak group has obtained Rh(0) NPs stabilized by ionic liquids (BMim+BF-4. OTf. The tests were performed in three systems: BMI⋅PF6. hydrogen pressure and oct-1ene concentration. A series of substituted aryl rings were used for the catalytic tests. G.= -O3SCF3. each. Dupont’s group synthesized metallic Rh(0) NPs in 1-nbutyl-3-methylimidazolium hexafluorophosphate ionic liquid ([BMI][PF6]) under H2 at 4 bar and 75ºC for 1 h [203]. ethylbenzene. and 1% metal wt. deuterated benzene.14 Rocío Redón. ionic liquids are commonly used as stabilizers of many metallic NPs. In a previous work. Kou’s group used poly[(N-Vinyl-2-pyrrolidone)-co-(1vinyl-3-alkylimidazolium chloride)] copolymer to stabilize metallic rhodium NPs reduced with H2 in 1-butyl-3-methylimidazolium tetrafluoroborate ionic liquid ([BMIM][BF4]) [206].or non-coordinating anions. They carried out kinetic studies in the temperature range 303-323 K. In a similar strategy. this group used the same method to carry out the hydrogenation of benzene [204]. García-Peña and F. The authors. The best results obtained were for benzene with 96% conversion and for phenol with a better TOF (247 h-1).and BtMA+NTf-2 [BMim+ = n-butyl-methylimidazolium. Roucoux’s group developed a series of catalytic hydrogenations with . BtMA+ = n-butyl-tri methyl-ammonium.5 h. TOF of 250 h-1 was obtained in 16 h. finding better catalytic activities for ionic liquids with hydroxyl groups and weakly. propylbenzene. synthesized through a solvolysis method. N. A series of hydrogenation catalytic tests were executed to correlate the results to the Raft equation. Before their silica supported catalyst investigations. Ramírez-Crescencio entrampment of Rh(0) NPs in simple solid ammonium salts by inducing their supercritic CO2 melting to form ionic liquids. With 3. When it comes to colloidal catalysts. this group reported the catalytic hydrogenation in benzene with the same NPs system [207]. benzene. and average turnover frequency (TOF) of at least 2000 h-1 are obtained. although poor conversion and a 74/26 ratio for the products cyclohexanol/cyclohexanone were achieved. Other aryl derivatives used were. The best results have been found for the solventless conditions with 21 h-1 TOF. and has been used in the hydrogenation of cyclohexene and benzene [201]. NTf-2 = N(O2SCF3)2]) through thermal decomposition of Rh6(CO)16 [202].4’-bipyridine system. The rate was found to be first order with catalyst concentration. For the hydrogenation of benzene. They compared the catalytic activity of the Rh(0) NPs in different ionic liquids using styrene hydrogenation as model reaction. The tests were performed in cyclohexene and yields up to 98% are obtained in 2. acetone and solventless. and styrene. is employed by Pellegatta and collaborators [211]. Other biphasic system (water-benzene). 100% conversion to ethylcyclohexane has been achieved. by Roucox and co-workers [208]. 75ºC. 1-octyne and 1-decyne. In this study. no hydrogenation was fulfilled. toluene and p-xilene. X=Br. with a 37% conversion in 4 h.1_-binaphthyl ((R)-BINAP) ligand and tetraoctylammonium bromide (TOAB). Better results were found when HEA16Cl was employed as stabilizer. 2-picoline. AlemánVázquez and collaborators have used alumina supported Rh NPs in the catalytic ring opening of cyclohexane [216]. They have obtained colloidal NPs via H2 decomposition of two organometallic precursors ([Rh(η3-C3H5)3] and [Rh(μ-OMe)(cod)]2) in the presence of two chiral diphophite ligands. and when this catalyst was used over disubstitued benzene derivatives. The best results were obtained with an impregnation route. The catalysis for the inverse CeO2/Rh thin film with a TOF of 4. achieved nanoparticles inside FSM-16 siliceous material by impregnation of the Rh salt. obtained poly(ethylene imine) amides (PEI) protected Rh(0) NPs [222]. and later supported on silica by impregnation was achieved Li’s group [220]. and 1. Other report. Other Rh(0) NPs used in the catalytic hydroformylation of styrene are the ones synthesized by Axet and coworkers [221]. and S-heterocycles. O-. Cl. In the same line of catalytic tests. respectively. 5 h-1 – 10 h-1 TOfs were detected. they realized catalytic studies in a biphasic system [215]. respectively. 92% branched selectivity and 25% ee (S-enantiomer) are achieved for the Rh-BINAP catalysts and 89% to 92% branched selectivity and 26% to 30% ee (S-enantiomer) for the Rh-BINAP/SiO2. in contrast to Rh/SiO2 were 0. 5% and 6-9%.7 and 7. al. These NPs were tested in the catalytic hydroformylation of styrene and vinyl acetate with a syngas flow. this group has obtained excellent results in a one pot hydrogenation-dehalogenation of chlorobenzenes [212]. The chemical reduced nanocomposite achieved >99% conversion with 88% selectivity for hydroformylation reaction. low total conversion are obtained.diastereomers are the major products (up to 99%).3. In their last article. obtained TOFs of 429 h-1. 3% and 2% production of n-propane and ethane. for CO hydrogenation. With appropriate conditions the authors. and 149 h-1 for anisole. quinoline. Although. As the Rh/PEI prepared via H2 reduction showed better results. explores the hydrogenation of N-. as pyridine. homogeneous catalyst and Rh/SiO2.3. the same group used this catalyst to hydrogenate CO [218]. Fukuoka et. Aditionally. furan. calcination under O2. For catalytic ring opening of methylcyclobutane. I. with better TOFs for furan to THF (200 h-1) and 1. In a previous work. When compared to unsupported Rh-BINAP. and subsequent reduction in H2 [219]. CH3SO3.15 h-1 TOF was achieved. This supported catalyst was used in the catalytic hydrogenolysis of butane and a TOF of 195h-1 has been achieved with 96% selectivity to the production of methane. In a previous work.70x10-2 s-1. hydrogenolysis or alcanolysis of different molecules and CO hydrogenation. 0. When chlorobenzene and 4-chlorotoluene were used in the catalytic tests. respectively.N-dimethyl-N-cetyl-N-(2-hydroxiethyl)ammonium salts (HEA16X. When thiophene and benzothiophene were used. 100% conversion has been achieved to cyclohexane and methylcyclohexane in 1. an experiment varying syngas pressure was . BF4). and stabilized only with N.5-triazine [213]. In each case. An interesting catalyst chemically reduced in presence of (R)-2. Tuchbreiter et. N-methylindole. Other reactions catalyzed by metallic rhodium NPs less reported include. CeO2 supported Rh(0) NPs are used in the catalytic ring opening of methylcyclobutane and hydrogenation of CO by Hayek’s group [217].5triazine (176 h-1). benzofuran.3. over catalytic hydrogenation of various benzene derivatives were investigated [214]. is found. a quantitative reduction has been found. al.2_-bis(diphenylphosphino)-1.55 h-1 TOF was detected. Regioselectivity up to >99% for the branched product with 40% of ee has been fulfilled. 256 h-1.Metallic Nanoparticles Nanocomposites 15 metallic rhodium nanoparticles synthesized via chemical reduction with sodium borohydride. the influence of the counter-ion in the surfactants. the cis. respectively. where the authors found better selectivity for hydroformylation catalysis at higher pressures. a number of excelent reviews have been published in the last years like Astruc´s [232-233]. When the catalysis was carried out over isopropyl alcohol.2Zr0. N. A catalytic related reaction is the hydrosilylation of multiple bonds. Other investigation to hydrosilylate aromatic nitriles was carried out by Petrici’s group [225]. The catalytic tests were realized under solventless condition and activated and deactivated aryl niriles were tested.15 at 400 K. Better oxidations were found for smaller NPs. Hasik and co-workers carried out tests with composites of Rh(0) and polypyrrole (PPy) [228]. They used γ-Al2O3 supported and unsupported Rh(0) NPs synthesized via Metal Vapour Synthesis (MVS). a Rh/Ce0. who focuses mainly in the catalytic Heck . where they found a correlation between the catalyst performance and the existence of different Rh(0). this group reported a catalytic sylilformylation reaction.16 Rocío Redón. In other work. the lower ones were achieved for the deactivated aryl nitrile. The titania supported NPs were obtained through lasser ablation. Dupont group applied their Rh(0) NPs synthezised via imidazolium ionic liquids to hydroformylate 1-alkenes [223]. realized studies of CO oxidation using a γ–Al2O3 supported rhodium catalyst [227]. with up to 1.69 s-1 TOFs. Quantitative conversions to aldehydes in 4 h were found. Palladium catalysis. to their catalyst. But two main catalytic reactions have been reported for palladium(0) NPs: reduction of alkenes and alkynes and C-C cross coupling. better conversions (80%) are obtained for benzonitrile and trimethylhydrosylane. Rh(I). García-Peña and F. and 90. In the catalytic oxidation of alcohols. when Senkan group used a Rh/TiO2 catalyst to fulfill the partial oxidation of propylene [229]. When the catalysts were calcined before use. Montini et. the authors determined that above 750 K the decomposition ethanol to H2.8/5. achieved a Rh/CexZr1-xO2-Al2O3 composite and used it for the ethanol steam reforming [230]. G. The reaction proceeded with regio. the water gas shift reaction is operative.51 ratio at 370 K. Acetone was also the main product. Longer time reactions are required to achieve the same results when the TOA unprotected catalyst is used. When it comes to palladium catalysis. and CO2 occurs. a clear indication that above that temperature. Newton et. many articles have been published in the last ten years. In a later paper. In a recent investigation. lower conversions (75-80%) are achieved.49/2. Although less information about this reaction is available. Somorjai’s group has reported studies of CO oxidation over rhodium NPs supported on SBA-15 [226]. In a previous reaction. acetone and propene were found as products in a 97.8O2Al2O3 catalyst was synthesized by the same method [231]. The authors report tests of a reaction in 1-hexyne. The supported nanoparticles denoted sensitivity to the aryl nitrile subtitution. adding trioctylamine (TOA). and it is impossible review all these investigations.36 at 430 K. with 25 ratio of lineal/branched aldehydes. In other report. as stabilizer. In other proceses. with a lesser degree of propionaldehyde and COx.64/9. In this work. 94. al. and obtained a quantitative conversion in 10 h with a 100% stereoselectivity for the (Z)-1-(Dimethylphenylsilyl)-2-formyl-1-hexene product. regardless the nitrile nature. when triethoxyhydrosylane is employed. al.and stereoselectivities to afford the (E)-1-silyl-1-alkene in 89% yield. Ramírez-Crescencio realized. and Rh(III) phases. In the last case. The system favors the dehydrogenation of ethanol to acetaldehyde. Quantitative conversions were obtained for the unsupported nanoparticles at 100ºC with trimethylhydrosylane (HSiMe3). CO. although some acetone formation is detected. Thiot and co-workers used a polyionic gels method to synthesize Rh(0) NPs and used these composites in the catalytic hydrosilylation of acetylene [224]. catalytic oxidation of molecules is also applied to metallic rhodium NPs. although the system was not sensitive to this variable. a decrease in the turnover frequency is registered due to the formation of Rh2O3. 1. TOF up to 10000 h-1 is achieved with quantitative conversions.1. For the conversion of cis-2-pentene. in 3 h. CNT are used as supports to synthesize palladium(0) NPs. up to 50% was achieved. Previous to these reviews. Hou and co-workers used the 2. Gomez et. The use of other ILs did not change the activity.3-tetramethylguanidine acetic acid (TMG+ AA-) ionic liquids to support palladium(0) NPs. and reduced under H2 flow. and mesoporous carbon (CMK-3) to support palladium(0) nanoparticles. Kiwi-Minster group explored the ionic liquid-carbon nanofibers (CNF) anchored to sintered metal fibers (SMF) stabilization of palladium NPs for a posterior use in the partial hydrogenation of acetylene under continuousflow conditions [246]. and cyclohexene. A review of great interest in our group is the one realized by Jesús and collaborators [239]. when CMK-3 and AC were used with a [NaOH]/[PdII] ratio of 4:1. made a review where informed about C-C cross coupling and hydrogenation reactions catalyzed by palladium NPs [237-238]. Trzeciak published a fine review.7x10-2 mol(gPdS)-1.3.680 hydrogenation/isomerization selectivity. and used them in the oxidation of benzyl alcohol and C=C hydrogenation of cinnamaldehyde [241]. ≈5% for 1-pentene. activated carbon (AC). homogeneous and heterogeneous. the catalysts prepared by the authors showed better activities in the 2-10 range of [NaOH]/[PdII] ratios. 1. 1. In a related investigation. al. and CB with a 8:1 [NaOH]/[PdII] ratio. used ionic liquid modified MWCNTs to obtain palladium catalysts and test them in the hydrogenation of different olefins [244]. with 80% selectivity for the hydrocinnamaldehyde. Harada et. a quantitative conversion is achieved. and 0. in 90 minutes. Mastalir group has achieved palladium(0) NPs encapsulated in graphite and used them to catalyze the hydrogenation of 1butene. When the 1-butene is tested. Farina has realized a study of high-turnover catalysts. Finally.3-dimethyl1-[3-N. Hydrogenation reactions. Chun et. with predominance for the catalytic isomerization. This report exhibits catalytic reactions carried out with dendrimer-supported palladium NPs. Tessonnier group used MWCNTs supported palladium(0) NPs for the selective hydrogenation of cinnamaldehyde into hydrocinnamaldehyde [243]. sepiolite clay is modified with 1. and ≈35% for pentane. al. Quantitative conversions were achieved in 25 h. and isomerization of 1-butene and cis-2-pentene [242].086 s-1 TOF. TOFs up to 2820 h-1 are achieved when styrene is used as substrate. On the other hand. dried.327 production selectivity of cis-2butene/trans-2-butene in the isomerization catalysis. For the oxidation of benzyl alcohol to benzaldehyde. al. with 0.3-tetramethylguanidine lactic acid (TMG+ LA-) and 1.3dimethylimidazolium hexaflourophosphate ([BMMIM][PF6]) ionic liquids to synthesize some palladium(0) NPs via H2 flow [247]. when 1-hexene and styrene are employed as substrates. where the author studied mechanistically the Heck reaction [234]. at 150º C. In the catalytic hydrogenation of cinnamaldehyde to 3-phenylpropionaldehyde. and use them in the reduction of alkenes and in the C-C cross coupling [245]. with a 60% production for the trans-2-pentene. The catalyst was synthesized by mixing an aqueous solution of H2PdCl4 and the previously modified sepiolite. Quantitative conversions were found when this NPs . the maximum activity (>80%) was achieved in an hour.3 tetramethylguanidine trifluoroacetic acid (TMG+ TFA-). quantitative conversion was fulfilled when Pd/CB was used with a 4:1 [NaOH]/[PdII] ratio. used in cross coupling reactions [236]. Selectivity up to 85% for ethylene was achieved with a rate of 3.3. When a commercial cPd/C was tested for this catalytic reaction. the type of investigation developed by our group [240].N-bis(2pyridyl)propylamido] imidazolium ([BMMDPA][PF6]) and 1-n-butyl-2. used carbon black (CB). cis-2-pentene.Metallic Nanoparticles Nanocomposites 17 cross coupling.1. no transformation was detected for cyclohexene.3. Jones´s group reviewed palladium catalysts used in the Mizoroki-Heck and Sukuki-Miyaura couplings [235]. styrene to ethylbenzene. and TOFs up to 727 h-1 for penten-3-ol. with NPs reduced in 1-propanol. Crooks and collaborators are one of the first groups in achieving dendrimer-encapsulated NPs. ethanol. This behavior is attributed to steric interaction between the substrates and the functional groups on the dendrimer periphery. employed a sonochemical preparation to produce Al2O3 supported NPs. The Pd reduction was carried out by an hydrazine solution. via H2 reduction of Pd(acac)2 dissolved in the before mentioned ionic liquids [248]. synthesized poly(acryonitrile-co-acrylic acid) supported NPs by electrospinning the copolymer-Pd solution [260]. with 72% selectivity for 1-butene. for the hydrogenation of allyl alcohols. Astruc group has achieved palladium NPs stabilized by “click” ferrocenyl dendrimers catalytically active in the hydrogenation of styrene [252]. After their experiments.3-butadiene. Ebert and co-workers obtained catalytically active poly(amideimide) nanofibre mat supported palladium(0) NPs for the hydrogenation of methyl-cis-9octadecenoate (methyl oleate) [259]. Dupont’s group stabilized palladium(0) NPs in 1-nbutyl-3-methylimidazolium hexafluorophosphate (BMI·PF6) or tetrafluoroborate (BMI·BF4). two possible products can be detected: the trans-isomer methyl-trans-9-octadecenoate (methyl elaidate) and the hydrogenation product methyl-cis-9-octadecanoate (methyl stereate). Metallic palladium NPs embedded in a PAA and/or PEI thin film. better catalytic activities were found (8088 h-1 TOF). This catalyst was . N. The best results were obtained with lower loadings. were used by this group in the hydrogenation of allyl alcohols [257]. In a previous work from this group. Bruening and co-workers synthesized α-Al2O3 supported poly(acrylic acid) (PAA) and polyethyleneimine (PEI) thin films. especially palladium and platinum nanoparticles obtained via chemical reduction with NaBH4 of a palladium salt [249]. they conclude that the process of hydrogenation of the methyl oleate takes place via isomerization reaction. In one investigation. Erman and collaborators.18 Rocío Redón. No byproducts were detected in any case. In other investigation. before and after electrospinning. TOF up to 3500 h-1 was achieved in the catalytic hydrogenation of 1-propen-3-ol. Also. especially with high generation dendrimers. 99% conversion is achieved. TOF up to 5880 h-1 was achieved for allyl alcohol. rate up to 700 mmol·(Pd-g)-1·min-1. The sonochemical reduction was carried out in the presence of alcohol additives (methanol. and a PAMAM dendrimer) to encapsulate or stabilize Pd(0) NPs and used the composites to reduce styrene to ethyl benzene [253]. When these dispersions are used in the partial hydrogenation of 1. These films are used as supports for metallic palladium nanoparticles [255]. Part of their investigation has focused in the correlation between the generation of the dendrimer used to encapsulate and the activity in different catalytic reactions. Ramírez-Crescencio were tested in the catalytic hydrogenation of cyclohexene to cyclohexane. al. In a recent investigation. this group used a series of dendrimers (triazolyl dendrimers. G. The best catalytic results that they obtained for a triazolyl dendrimer first generation with 27 dendronic-9-propyl units with up to 3390 h-1 TOF when methanol was used as reducing agent. this group tested dendrimer-encapsulated palladium(0) NPs in the catalytic reduction of allyl alcohols [250-251]. Okitsu et. with a 500:1 substrate/Pd ratio. triaziolylferrocenyl dendrimers. all supported onto alumina. triazolyl dendrimer-encapsulated Pd(0) NPs were tested in the catalytic hydrogenation of allyl alcohols by Astruc group [254]. They have found selectivity for lineal substrates. the same catalyst was used in the hydrogenation of allyl alcohols [258]. When these nanoparticles were tested in the catalytic hydrogenation of 1-hexene and trans-3-hexene. García-Peña and F. When the catalytic tests were carried out. and 1-propanol). for the hydrogenation of 1-hexene. When a zero generation was used. and ethyl actylate to ethyl propionate at 35º C. the catalytic reaction is tested when the catalyst loading is varied [256]. 56 s-1 with 8. when 10% loading of flame spray made catalyst is used. Jayaraman’s group modified silica with poly(ether imine) based dendritic phosphine ligands to support palladium(0) NPs [263].2 s-1. 1. before and after addition of SiO2 precursor (Na2Si3O7). up to 11.4-diol and phenylacetylene [269]. Other report from this group sinthezised palladium(0) NPs stabilized in block-copolymer micelles and used them in the selective hydrogenation of 2-butyn-1. The n-dodecyl sulfide stabilized NPs were achieved by reducing with hydrazine hydrate and sodium hydroxide in presence of n-dodecyl sulfide. although a 1:1 ratio is achieved in the production of 1-cyclooctene and cyclooctane. by NaBH4 or ascorbid acid reduction of H2PdCl4 in presence of cetyltrimethylammonium bromide (CTAB) [266]. in 4 h or less. TOF up to 5. and used the NPs in the same catalytic reaction [267].7% conversion was achieved in the case of 1-hexyne with 100% selectivity to 1-hexene. this group used the same catalyst in the same reaction to compare its performance with an impregnation made catalyst. In other experiment. the same results were found for the reaction of 6-bromo-1-hexene to 1bromohexane. this group achieved shape defined palladium NPs. Obare’s group used a series of supported and unsupported Pd(0) NPs to catalytically hydrogenate styrene. When this catalyst was used in the hydrogenation of various olefins. via flame spray pyrolysis method. In a recent investigation. was used to support palladium NPs. Mastalir et.7-dimethyloct-6-ene-1-yne-3-ol. In the reduction of phenylacetylene to styrene. etc.5% selectivity to the trans-3-hexene product.34 s-1) with 8. A gel type resin (FCN) as a result of copolymerization of glycidyl methacrylate (GMA). quantitative reactions were obtained in each case. with quantitative conversions in the reaction of styrene to ethylbenzene. in the hydrogenation of 1. The catalysts were obtained by hydrazine reduction. although from this product. A similar result was reached for the conversion of 3-hexyne (5. with a 75% conversion. decomposition. have synthesized SiO2 supported palladium(0) NPs. using tetradecyltrimethylammonium (C14TABr). In a previous article. these NPs were supported over silica. to use them in the partial hydrogenation of 1-heptyne [261]. up to 50% suffers other processes like isomerization. TOF up to 66. at 25º C. using ethanol as solvent. These NPs were used in the catalytic hydrogenation of 2-methyl-3-butyn-2-ol. with 42% conversion and 93% selectivity for the 1-heptene product. and test them in the hydrogenation of 2-butyne-1. and 6bromo-1-hexene [262].4diol product was obtained with a total of 90% conversion.4-diol [268].Metallic Nanoparticles Nanocomposites 19 tested in the selective hydrogenation of dehydrolinalool (3. An increase in the palladium loading did not increase the rate of .5-cyclooctadiene. with palladium acetylacetonate and tetraethylorthosilicate (TEOS) as palladium and silicon precursors. quantitative conversion was found. DHL).3 reaction rate is achieved when the catalyst is synthesized when a high concentration of acrylic acid co-polymer was used and the reduction was carried out after electrospinning. styrene.91 s-1 was achieved when the alumina supported catalyst was used.2 s-1 has been achieved.2% conversion and 94. 94% selectivity is reached in a quantitative reaction. In a recent experiment.4-diol. al. TOF up to 0. Up to 95% selectivity for 1-heptene is achieved. For the hydrogenation of 2-butyne-1. Better results were achieved by Minsker group in the selective reduction of 1-hexyne to 1-hexene (9. with up to 91. and ethylene glycol dimethacrylate.4% selectivity to styrene. the group used PdCl2(NH3)4 as metal precursor. in 85% conversion with 96. tested MCM-41 supported palladium(0) NPs and tested in the hydrogenation of alkyne reductions [264]. on the other hand. the catalyst yielded 90% of total conversion. Somboonthanakij and collaborators.5 selectivity) [265]. up to 92% selectivity for the 2-butene-1. The best results were achieved with the largest Pd spheres. The best conversions were obtained for the silica supported NPs.5cyclooctadiene. 90 min. When the catalysis was carried out in super critic conditions. drying. quantitative reactions were achieved in 30 min. with up to 68% selectivity for the citronellal (CIAL) product. By their way. Ramírez-Crescencio hydrogenation or the selectivity.3-butadiene (0. were developed by Underhill et. Lower but good conversions were carried out in benzene and phenol in 60-50 minutes. al. The palladium reduction was carried out in supercritical CO2. In other investigation.20 Rocío Redón. penylacetylene.2%. kinetic studies were carried out to determine the effect concentration of NaBH4. each. A colloidal system of palladium(0) NPs were obtained by Wai and collaborators to hydrogenate 1-phenyl-1cyclohexene.9%. and 100% selectivity for ethylbenzene. >50% conversions were detected after 9 minutes of reaction. in presence of the nanotubes. Murugadoss and co-workers . The main catalytic reaction reported with metallic silver nanoparticles is the reduction of nitrogen compunds. maleic acid and nitrobenzene >99% conversion were detected in almost each case (>95% conversion for styrene) in 20 s to 30 min (for the reduction of nitrobenzene to aniline). ethylbenzene. and later loading the palladium(II) composite into a reactor and producing the super critic CO2. with a 93% selectivity for the ester product. Sastry and collaborators obtained a H-Y zeolite grafted with amine groups to support Pd(0) NPs [279]. The catalyst was prepared by mixing palladium(II) hexfluoroacetylacetonate (Pd(hfac)2) with SBA-15 in THF. Lee and co-workers used a supercritical CO2 system to synthesize mesoporous silica SBA-15 supported Pd(0) NPs to hydrogenate the 4-methoxycinnamic acid benzyl ester [276]. the group used high density polyethylene (HDPE) granules and fluoropolymer (PFA) tube to support Pd(0) NPs [274]. have immobilized PVP supported silver NPs onto halloysite nanotubes through reduction of AgNO3 by polyol process [280]. and poly(acrylic acid) (PAA). and 40 min. and nitrobenzene. >99% conversion was achieved in less than an hour. al. This catalyst was used in the hydrogenation of transstilbene. Liu et. Other work from this group reports the same catalytic system [278]. Silver catalysis.80 s-1 TOF). respectively. surfactants like cetyltrimethylammonium bromide (CTAB) were used to stabilize palladium(0) NPs. 85. García-Peña and F. N. with a H2 flow. with 99. cross-linked poly(2-cinnamoyloxyethyl methacrylated) (PCEMA). The best results were found when prism-like NPs were used in the catalytic reduction of 1. also used a super critical CO2 to synthesize Pd(0) NPs. 96% conversion is achieved in 10 min of reaction. Piccolo and co-workers used this cationic surfactant to produce well defined palladium NPs in dispersion [271]. Recently. This composite was used in the reduction of 4-nitrophenol to 4-aminophenol. When tested in the hydrogenation of styrene. In the catalytic hydrogenation of 4methoxycinnamic acid. Meric et. al. G. When it comes to colloidal systems. and quantitative monoreduction of naphthalene was achieved in 10 minutes with the HDPE supported Pd(0) NPs. methyl methacrylate (MMA) and ethylene glycol dimethacrylate (EGDMA) [270]. trans-stilbene. Quantitative conversion was achieved when 150 bar of CO2 was added to the hydrogenation reaction. vinylacetic acid (VAA). The catalysis was improved when the tests were carried out at a pH=10. The deposition was the same. this group used a water-in-CO2 microemulsion to obtain palladium NPs and use them in the reduction of a number of olefins [275]. In a previous work. This group combined H2SO4-HNO3 modified MWCNTs and supercritical conditions to support Pd(0) NPs [273]. methyl trans-cinnamate and trans-stilbene [272]. and aniline. which were used in the catalytic hydrogenation of citral [277]. Nanospheres derived from hydroxylated polyisoprene (PHI). to encapsulate palladium(0) NPs and test them in the catalytic reduction of triethylallyl ammonium bromide (TEAA). When this catalysis was tested in 10-(3-propenyl)anthracene. In a recent investigation. Debecker and co-workers obtained silver NPs via multiple layers surfactants and latter supported over TiO2 or V2O5/TiO2 by wet impregnation. Other group of reactions commonly catalyzed by metallic silver NPs is the oxidation of molecules. This nanocomposite. achieved colloidal silver NPs reduced with NaBH4. Pradhan et. different phenylsilanes were used. By their side. Qian group carried out a similar investigation [282]. They report better photocatalytic results with the NPs obtained via chemical reduction. The reports on osmium metal nanoparticles have been focused on the synthesis. Kaneda’s group has explored the catalytic oxidation of phenylsilanes to silanols [291]. Again.6 – 1. when tris n-butylsylane and t-butyldimethylsilane were tested. they didn’t report any possible product in the reaction.N-dimethylformamide (DMF) in the presence of PVP. 99% conversion was obtained. Faster results were found with the NaBH4 reduced NPs. Obtaining a TOF value of 1. while the HMTA reduced catalyst showed low activity at temperatures slightly above room temperature. with a 99:1 selectivity for dimethylphenylsilanol. In contrast. and ascorbic acid [283]. In a related catalytic reaction. no catalytic activity was found. CO. al. al. reached a total degradation within 11 min. who used microfiber supported silver NPs to reduce methylene blue [285]. More investigations have been developed in the degradation of commercial dyes. When the formaldehyde reduced catalyst was tested in the CO oxidation. The best catalytici results were obtained with cubic NPs in 12 h with 82% conversion. The Os nanoclusters can be separated from the reaction system as a precipitate and the precipitated can easily ‘‘dissolve’’ in many organic solvent such as acetone and THF to form stable colloidal solutions. The truncated triangular silver NPs were synthesized by a solvothermal method in N. Gyenge et. When dimethylphenylsilane was used. and conversions of 96% . along with NaBH4. Osmium. In a previous work. Rupa and collaborators have used TiO2 supported NPs to photodegradate the commercial dye Reactive Yellow-17 (RY-17) [284].99% were achieved in each case. although they do not report which products were obtained. [293] used tetrabutylammoniumtriethylhydroborate . al. although its catalytic maximum (100%) was reached at 230ºC. and used them in benzene oxidation to CO2 and H2O [289]. [292] obtained an average particle size of the Os nanoclusters in a stable colloidal solution of 0.9 nm with a size distribution of 0. Their catalyst are hydroxyapatite (Hap) supported silver NPs. Other catalytic degradation carried out by metallic silver nanoparticles is the phenol degradation. At 10 min.8 nm (σ:0. The Ag-V2O5/TiO2 showed better conversion (100%) at 350ºC than the Ag-TiO2. Li and collaborators obtained silver NPs with well-defined shapes and used them to oxidize styrene to benzaldehyde and styrene oxide [288].5% conversion. In a slightly different reaction.28). no catalytic activity was detected below 150ºC and its maximum activity (100% conversion) was detected at 270ºC. N2H4.Metallic Nanoparticles Nanocomposites 21 embedded silver NPs inside a chitosan matrix [281]. Dai’s group supported silver NPs over TiO2 with a twistlike helix structure [287]. An experiment was carried out in the absence of the silver NPs. Tian and collaborators obtained Ag/SBA-15 catalysts prepared through an in situ reduction method using hexamethylenetetramine (HMTA) and formaldehyde as reducing agents and used them in the catalytic oxidation of CO [290]. A 81:19 ratio for benzaldehyde was achieved. they have achieved a 71. and no degradation was observed. Kundu and co-workers used this catalytic reaction to sense low concentrations of ammonia in solution [286]. thus Wang et. like the one realized by Demir group. They have supported the silver NPs over a cuttlebone derived organic matrix (β-chitin) by reducing via Tollen’s reagent and NaBH4.5x10-3 s-1. 8 nm. Cunha and Cruz [303] reported decreased activity for very small metal particles (1-2 nm) in the study of the hydrogenation of benzene and toluene over Ir /γ-Al2O3. al. using this system for the catalytic oxidation of ethanol. Iridium-based films on Au electrode surface have been synthesized by Birss et. Stowell et.2S)-diphenylethylenediamine as chiral modifier to improve the dispersion and stability of the Ir particles. [305] have used presynthesized iridium nanocrystals stabilized by weakly bound tetraoctylammonium bromide (TOAB) ligands to be infused into presynthesized mesoporous silica using CO2 and toluene to produce an active catalyst for 1-decene hydrogenation.oxidation. Yang et. al. al. [304] have obtained Ir NPs supported on SiO2 using cinchona alkaloids and (1S. Osmium islands deposited on Pt (111) have been synthesized by Strbac et. This catalyst was proved to be active for hydrogenation of various arenes and ketones under mild conditions. obtaining a mean particle size of 2. Ir nanoparticles (~3. The NPs prepared have a mean diameter of 1. explains their relatively low stability that leads to aggregation/agglomeration and eventually to the bulk metal. al. al. Dupont et. A good catalytic performance in the asymmetric hydrogenation of acetophenone in MeOH was obtained. [306] have used a reversed micelle technique to obtain hollow silica nanospheres (~35 nm) containing Ir NPs (1-2 nm) for studies in hydrogen storage. Reduction of [(1.N-dimethyl-N-cetyl-N-(2-hydroxyethyl)ammonium chloride salt. but on the other hand. Catalyst was recupered by simple filtration. Os NPs are electrochemically active for BH4. is responsible to some extend for their catalytic activity. [307] have reported the synthesis of iridium NPs in aluminum oxyhydoxide Ir/AlO(OH). Due to the reaction is carried out in two phases. . Yinghuai et. sol-gel solution showed Ir NPs of 1-2 nm average size and IrOx were not detected. al.5 nm) are used for borylation of benzene and catalyst is recyclable by extraction of impurities. al. Catalyst can be recycled by centrifugation-decantation method.22 Rocío Redón. [297] have realized several studies about synthesis of nanoparticles in different ionic liquids(ILs). This catalytic suspension was efficient for hydrogenation of benzenederivatives such as mono or disubstituted arenes and provides the corresponding saturated compounds. al. G.4 nm. high selectivity(100%) acetone hydrogenation catalyst [298]. onto the support and into the decene during reaction. catalyst can be reused after simple decantation in a separating funnel without a significant loss of activity. al. [300] have obtained iridium NPs using a different ionic liquid as stabilizer. their results indicate that IL reacts with the nanoparticle surface and generate surface-bound protective species which on the one hand. where desorption of ligands from the adsorbed nanoparticle surface. where. Ramírez-Crescencio (C4H9)4N[BH(C2H5)3] as both reductant and stabilizer. This catalyst was used for opening the cyclohexane ring showing better results than Rh/Al2O3. will enhance metal binding to the surface and aid catalyst stability. Mévellec et. Park et. So.5-COD)IrCl]2 by H2 in neat acetone yields 1 equivalent of H+Clfor each Ir(I) reduced to iridium(0) resulting in a highly efficient (100%). Yung and coworkers [294] have synthesized Os NPs supported on MWCNTs by vacuum pyrolysis at 573 K using [Os3CO10(NCMe)2] as precursor. the ligands must be strong enough binders to stabilize nanocrystals but weak enough to provide reactant access to the metal surface. They found that “good” capping ligands appear to be poor choices for catalytic applications. RodríguezGattorno et. Miyao et. [295] and Pacheco Santos et. García-Peña and F. al. [299] have obtained aqueous suspensions of Ir NPs through chemical reduction of IrCl3 assisted by sonication in the presence of a surfactant: N. al. N. [308]. Gupta et. [296]. Iridium. [301] have synthesized iridium NPs in the presence of different capping ligands to hydrogenate 1-decene to decane. acid-assisted. [302] have prepared iridium NPs supported on Al2O3. al. room temperature and even with an hydrogen balloon. [320] have studied the hydrogenation of isophorone at room temperature and pressure H2=2 bar with platinum NPs. the total Pt surface area decreases as the sizes of the DENs decreases. al. poly(benzimidazole) (PBI) and Pt nanoparticles. Ethylene and pyrrole hydrogenation reactions were studied. Presence of nanoparticles within the dendrimer layers are important to demonstrate the charge storage effect for non-volatile memory applications while the dendrimer layers act as a host network to trap the Pt nanoparticles. toluene hydrogenation and CO oxidation were studied. al. [317] have obtained platinum NPs of different sizes and small narrow size distributions. Recently Knecht et. Using a G6-OH PAMAM dendrimer. This decrease is attributed to the increase of the dendrimer adsorption on the metal nanoparticles. Using other dendrimers as stabilizers for Pt NPs. Ye et. and it was found that the activity was increased to a certain temperature. then NPs were immobilized onto mesoporous silica SBA15. Dendrimer encapsulated nanoparticles (DENs) are immobilized in a glassy carbon electrode and are used for oxygen reduction reaction (ORR). [316] have obtained Pt NPs within a ultrathin film matrix formed by covalent layer-by-layer assembly of pyromellitic dianhydride (PMDA) and second generation PAMAM dendrimer in supercritical CO2. In the same way. [321] have obtained a nanocomposite made of MWCNTs. [311] have synthesized platinum NPs stabilized with a PAMAM G4OH dendrimer. This behavior is explained by a partial decomposition of dendrimer capping. Yang et. After removal dendrimer. they proposed that low generation assemblies do not provide kinetic barriers to prevent NPs aggregation into larger metal clusters. After. Lang et. al. They found that the average particle sizes of the metal nanoparticles are almost independent of the concentration of the dendrimer as well as the generation for both the PAMAM and the PPI dendrimers. Platinum NPs supported over hypercrosslinked polystyrene (HPS) have been synthesized by Bykov and collaborators [319]. Modification of Pt/HPS catalyst with cinchonidine gave better results for enantioselective hydrogenation of ethylpyruvate. silica was added to a Pt-G4OH. Du et. al.Metallic Nanoparticles Nanocomposites 23 Platinum. When the size of DENs was reduced. al. The catalytic activity of the dendritic catalyst decreased with the increase of the generation of the dendrimer. Okamoto et. [318] have reported that dendrimer complexes with Pt2+ are not fully reduced when exposed to BH4. this can be explained considering that larger dendrimers could limit the accessibility of the substrates into the active centers of platinum nanoparticle-cored dendrimer. al. also. Such nanoparticles are used to carry out hydrogenation of nitrobenzene derivatives with molecular hydrogen under mild conditions. lower ORR activity was observed. [312] have used hydroxyl terminated PAMAM G4 dendrimers to stabilize platinum NPs obtained by reduction of Pt2+ with hydrogen. the rate constants decrease with increasing dendrimer concentration. al. Marty´ et. al. The nanocomposites were used for reduce 4-nitrophenol to 4-aminophenol. al. In order to “activate“ the catalyst. [309] have obtained platinum NPs stabilized by polyaryl ether trisacetic acid ammonium chloride dendrimer through an alcohol reduction method. Michels et. MWCNTs are wrapped with PBI . [314] have used poly(propyleneimine) (PPI) dendrimers and PAMAM dendrimers to stabilize platinum NPs. al. al. al. [313] have used PAMAM G5 OH dendrimers to obtain stabilized platinum NPs that were deposited on SiO2. [310] have carry out the hydrogenation of phenyl aldehydes to phenyl alcohol under an atmospheric pressure of H2. Puniredd et. the dendrimer was removed via calcination.in aqueous solutions. [315] have obtained platinum NPs stabilized by supramolecular dendritic assemblies of β-cyclodextrins and PPI dendrimers. Huang. Deutsch et. NaBH4 and different amounts of K2PtCl4. This film matrix is immobilized onto SiO2. Esumi et. et. Changing liposomes type. Comparing PPy-Pt/GCE with Pt/GCE they have found that the activity and stability of the Pt nanoclusters embedded in PPy nanowires were higher than pure Pt deposited on electrode. al. al. [333] this method have the advantage that do not need an additional reduction agent. Using Pt PVP-protected NPs as precursor Lin et. Liu et. al. [325] have reported that generation in situ of platinum seeds and autocatalytic growth in presence of surfactants leads to two. [334] have synthesized platinum nanoparticles reducing H2PtCl6 with ethanol in presence of PVP. 298 K and hydrogen at 0. [328] have synthesized platinum NPs encapsulated on Al2O3. They found that activity of PPy-based composite was higher than the exhibited by the PANI-based one. have been employed by Tang et. Dendrimer encapsulated platinum NPs functionalized with glutamate dehydrogenase and supported on CNT. [332] over a glassy carbon electrode (GCE). Dendrimers also play a role as stabilizers for the particles. That have been used for hydrogenation of phenyl aldehydes.and three-dimensional platinum nanodendrites. al. Such nanostructures were used for hydrogenation of propene. al. al. al. [335] to build a multilayer biosensor of glutamate. This fact was explained by the authors by the presence of different acidic centers in the polymers. Modifying PVP and ethanol amounts can obtain different particle sizes. Kostelansky et. Using a Pt/PVP colloidal solution in methanol. Wang et. Song et.al. Collier et. [337] have stabilized Pt NPs with the water-soluble phosphine ligand tris(4phosphonatophenyl)phosphine (TPPTP). Platinum particles supported on polypyrrole (PPy) and polyaniline (PANI) have been used by Hasik et. [324] have obtained platinum NPs supported on the outer surface of MWCNTs by reduction of PtMe2COD using hydrogen on supercritical CO2.1 MPa. Pd and Ru NPs. N. García-Peña and F. Li et. [326] have reported crown-shaped platinum NPs using UV irradiation in the presence of G4-NH2 PAMAM dendrimers in water. The composite was used for methanol oxidation and have higher efficiency than carbon black/Pt system. [330] have achieved hydrodechlorination of monochlorobenzene to benzene and finally to cyclohexane with high catalytic efficiency. al. al. Platinum NPs embedded in polypyrrole(PPy) nanowires have been synthesized by Li et. Synthesis of platinum-polystyrene nanocomposite through an alcohol-reduction method has been studied by Kim et. [327] to catalyze the isopropyl alcohol conversion. Bayrakceken et.24 Rocío Redón. [331] have obtained a Pt/PVP@MCM-41 composite (MCM-41: mobile crystalline material) which is active in the conversion of cinnamic acid in their corresponding hydrocynnamic acid. Using a surfactant (SDS) in the synthesis of Pt NPs they have obtained superior polymer electrolyte membrane (PEM) fuel cell activity. and were used for electrocatalytic oxygen reduction and methanol oxidation. These NPs were used for the enantioselective catalytic hydrogenation of ethyl pyruvate and shown similar results that previous supported analogous. al. sheetlike nanodendrites or foamlike nanosheets of platinum can be obtained. G. Taylor et. Advantage of this system is attributed to a protection effect of the 3D structure of the composite to poisoning. The negatively charged TPPTP-Pt NPs were . [323] have obtained Pt/SWCNTs composite in supercritical methanol. Zhu et. [336] have used Octa(diacetic aminophenyl) silsesquioxanes (OAAPS)to stabilize Pt. [329] have prepared solvent stabilized Pt NPs by the electron beam evaporation of the metal and co-condensation with the vapours of organic solvents at 77 K in a Torrovap metal atom reactor. al. Ramírez-Crescencio and deposition of Pt nanoparticles was carried out via polyol method. al. [322] have obtained MWCNT/PANI composite films supporting electrodeposited Pt NPs. The composites were used for the electrochemical oxidation of formic acid. al. this support provides small diameter and size distribution due to its pore dimension. Luo et. al. al. Yoo et. but the method described by Brust and its variation are one of the most popular synthetic schemes in the field [342]. al. [345] have mentioned that synthesis of dendrimers is prohibitive for many applications because of the high cost of the dendrimer synthesis although hyperbranched polymers can be easily accessible and they can effectively stabilize metal nanoparticles in organic solvents. [340] have proposed the use of S layers from S. [351] have obtained better results not only with 1-phenylethanol but with several alcohols at room temperature under atmospheric conditions. [346] have synthesized gold NPs in the matrix of a plasticized anion-exchange membrane. However. Catalytic performance of Au/polymers over oxidation of glucose with H2O2 was affected by the kinds of polymer supports and has less influence by the size of Au nanoparticles. [349] for studying the reduction of 4nitrophenol to 4-aminophenol and it was compared with other reported supports for the same reaction. Niesz et. al. PMMA as polymeric support of gold NPs have been used by Kuroda et. leads to slower . Park et. after poly(2-vinyl pyridine) (P2VP) chains are adsorbed to the surface of these particles and then gold NPs are prepared in P2VP brushes. There are numerous routes for the production of colloidal Au(0) nanoparticles. polystyrene (PS).The results indicate that the structures of polymer supports play an important role in determining the catalytic activities. Ishida et. al.al. Addition of anionic Pt salt under flowing H2 gave larger NPs. Wu and coworkers [347] have developed a method in which nanocomposite with hydrophilic clay faces and hydrophobic polystyrene (PS) brushes in the edges are used to stabilize PS colloidal particles. radiodurans as a biomolecular template to order arrays of dendrimer encapsulated platinum NPs. between dendrons. provide regular 2D arrays. They argue that the increased steric congestion. Tang et. Gold nanoparticles functionalized with carbohydrates (glyconanoparticles) have been synthesized by several groups [343]. al. acidocaldarius and D. [348] have deposited gold NPs onto polymer beds such as poly(methyl methacrylate) (PMMA). Using a hyperbranched polymer chemically analogous to PAMAM dendrimers. [350] They argue that the bad performance of the Au nanoclusters may be partially related to their large size. and hyperbranched polymer showed better results than its corresponding linear analog. poly(vynilchloride) (PVC) and melamine-formaldehyde resin (MF). Platinum-silica aerogel nanocomposites have been synthesized by a supercritical impregnation method by Yoda and collaborators [338]. al. Mark et. This approached. al. Miyamura et. Using a four dendritic thiol ligands. they have obtained gold nanoparticles. al. Gold. [339] have obtained Pt NPs by reduction of H2PtCl6 in water with NaBH4 in the presence of the capping poly(ethylene oxide)13-poly(propylene oxide)30-poly(ethylene oxide)13 triblock copolymer at room temperature. have been developed by Biffis et. where gold NPs are dispersed throughout the matrix of the membrane but excluded from the surface. Pérignon et. polyaniline (PANI). [341] have obtained a Pt/PPy nanocomposite by means of ultrasonic irradiation in the presence of sodium dodecyl sulfate or poly(N-vynil-2-pyrrolidone). Kumar et. [344] have found that large citrate protected gold nanoparticles (around 17 nm) can be extracted from water into chloroform using hyperbranched polyethylenimine (HPEI) polymers. These results were obtained using gold nanoclusters stabilized with polystyrene. Advincula [352] have found that average size of gold NPs increases while the sizes distributions becomes broader as the size of thiophene dendron increases. Oxidation of 1-phenylethanol with dioxygen in water catalyzed by microgel-stabilised gold NPs with poor results.Metallic Nanoparticles Nanocomposites 25 electrostatically deposited onto a glassy carbon electrode (GCE) modified on multilayers and are used for oxygen reduction reaction (ORR). al. al. Gold nanoclusters capped by dendron thiol-terminated Fréchet-type benzyl ether dendrons (G1) have been synthesized by Li et. The separation between the rows corresponds to 1. resulting in the formation of larger gold clusters and broader size distribution. al. al. Again. Mertens et.3 times the length of the dendron in its fully extended conformation.2 ± 0. These clusters are stable in aqueous solution for several years. García-Peña and F. a poly(aryl ester) dendron was used by Frein et. Ramírez-Crescencio reaction with the growing Au nanoparticles. functionalized dendrons using DTT. [364] They have obtained NPs in biphasic media using tetraoctylammonium bromide (TOAB). [363] have obtained gold clusters capped with tetrahexylammonium bromide. al. [370] have studied the . The size and shape of Au-NCDs (nanoparticles-cored dendrimers) change with the generation number of dendrons [354]. The Au atoms in the G1-gold clusters were largely Au(0). For the 4th generation dendrimer (G4) the autoreduction process is much faster compared to the low generation dendrimers G2 and G3. Using a two-phase method Rodríguez-Vázquez et. Olefin metathesis can be achieved on the surface of gold nanoparticles [368].26 Rocío Redón. [365] have obtained gold nanorods via oxidation of spherical gold nanoparticles using NaH2PO4 in the medium of cetyltrimethylammonium bromide (CTAB). Love et. N.and tridimensional arrays [367]. Bakshi et. al. the reduction of metal ions is practically instantaneous. [353] using poly(oxymethylphenylene) dendrons (PPD) of generations (G) 1-4 functionalized with a thiol group at the focal point as capping ligands. Using maltose-modified PPI dendrimers (generation 2-5). al. Fabrication of hydrophobic gold nanorods from hydrophilic one have been developed by Mitamura et. [357] have obtained nanoparticle-cored dendrimers (NCDs) through the synthesis of monolayer-protected nanoparticles and then adding dendrons on functionalized nanoparticles by a coupling reaction.not just the simple steric effect of dendritic ‘size. In order to functionalize gold NPs. polymerization of aniline and formation of Au nanoparticles (average size 5 nm) are simultaneously achieved in the presence of γ-irradiation. it is mentioned that nature of the support must be taken into account in order to explain the catalytic behavior of these catalysts.4nm. the structural nature of the dendritic branching must play a role in controlling nanoparticle growth . al. Pietsch and collaborators [361] have obtained gold NPs using NaBH4 or only dendrimer as reducing agent. Tomalia and Huang [358] have reported Cystamine core (G1–3) PAMAM dendrimers reduced to their respective thiol core.’ Shon et. Huang et. through a one pot synthesis. water. a composite made of SWNT-PANI-Au. indicating that also. Krasteva and coworkers [360] have found that resistivity and vapor-sensing properties of chemiresistors made from gold nanoparticle/poly(propyleneimine) composite films depend on the size (generation) of the dendrimers. al. Gold NPs supported over TiO2. Al2O3 and SiO2 have been used by Zanella and collaborators [369] for the water gas shift reaction. toluene and NaBH4 obtaining nanoparticles ordered in evenly spaced rows. Lee et. The average size of the nanoparticles was 1. CeO2. [355] Size-controlled gold nanoparticles were obtained by the variation of the mole ratio of G1 to Au. al. in the case of G5 dendrimer. [356] have determined that using branched ligands leads to smaller and better defined Au NPs than using an analogous nondendritic stabilizer. When increasing the generation number of dendrimer the size of the gold nanoparticles increases and polydispersities too. al. al. [359] have obtained gold NPs in aqueous phase in the presence of sodium dodecylsulfate (SDS) and dodecyltrimethylammonium bromide (DTAB) and poly(amidoamine) dendrimers (PAMAM). [362] have reported. G. al. One-dimensional arrays of Au-dendrimer nanocomposites have been obtained by Torigoe et. [366] DNA-based gold nanostructures have been synthesized by several groups obtaining bi. polymers that are part of the composites help nanoparticles to work better as catalysts by lowering costs. efficient and non-contaminant. al. Au over SiO2. not only at the bottom. Gold NPs supported on TiO2 were used by Raptis et. Diao et. supports. [371] have studied the synthesis of hydrogen via methanol oxidation using gold supported on CeO2. the activity being correlated with the metal's high standard electrode potential was reviewed by Bond and Thompson [376]. [375]. they demonstrate that intermediates of reaction involves organo-gold species. [381] and used for epoxidation of alkenes with O2. [374] have studied the ethanol dehydrogenation by gold nanoparticles supported on mesoporous sillicas and conventional sillicas obtaining different particle sizes. al. activated carbon and SiO2. but everywhere in order to find the “dream catalyst”. Au is more resistant to deactivation by chemical poisoning or overoxidation and it displays a higher intrinsic chemoselectivity. al. [379] have prepared a catalyst of MWNT. . al. Supported gold chloride is the most active catalyst for the hydrochlorination of ethyne. Br-. MgO. Santosh et. al. which was used to demonstrate electrocatalytic oxidation of methanol and CO. Guan et. MgO. Au sols were prepared by reduction of HAuCl4 with NaBH4 in an aqueous solution of poly(vinylalcohol).2-diols to α–hydroxy-carboxylates with gold nanocolloids They argue that in comparison with Pt and Pd. templates or protectors. as mentioned above. poly(dimethylsiloxane) or DESAL-5 DK) and then reutilized without significant lose of activity. by being environmentally friendly or through a combination of these applications. by increasing their selectivity and/or reactivity. [373] have reported that the oxidative lactonization of diols using molecular oxygen as a primary oxidant can be catalyzed by Hydrotalcite supported gold NPs. [377] have reported that gold submicroparticles (AuSMPs) dispersed on indium tin oxide (ITO) are catalytically active toward CO electrooxidation in solution. Oxidation of nitic oxide can be catalyzed by TiO2-Au nanocomposite film electrode as reported by Milsom et. CeO2 and C for studying the oxidation of benzylic compounds into their corresponding ketones without solvent at 1 O2 atm and T ≤ 100°C. the best catalyst which is cheap. the study of this kind of materials is still growing and. Mitsudome et. I-) exhibit significant poisoning effect on the catalytic activity of AuSMPs/ITO electrodes. cellulose acetate. Al2O3. TiO2 and silylated materials have been synthesized by Aprile et. [378]. Maximum activity for alcohol dehydrogenation was observed at a particle size around 6 nm. providing a new twist on Feynman's famous quote. Thus. there is a promising future and still a lot of work to be done to get the best catalyst ever designed. Gazsi et. recoverable. it is necessary to keep in mind that there is plenty of room. Al2O3.Metallic Nanoparticles Nanocomposites 27 catalytic oxidation of several 1. Films have 3050 nm per layer and gold NPs exhibit a 20 nm average diameter. TiO2. Dapurkar et. al. polyaniline (PANI) and gold nanoparticles (8-10 nm) MWNTPANI-Au. obtaining gold NPs with average size of 2-4 nm. CONCLUDING REMARKS AND FUTURE PROSPECTS As matrices. Methanol oxidation over Au/TiO2 (prepared by deposition precipitation method) catalyst have been studied by Nuhu et. al. al. [372] have used gold NPs (less than 10 nm) supported on TiO2. al. Thus. recyclable. They also found that the halide ions (Cl-. this catalyst was recovered by filtration through a membrane (polyimide. al. [380] as a heterogeneous catalyst for the isomerization of epoxides to allylic alcohols in high yields and good selectivity. Sc. Ana A Albeniz at Valladolid Unive ersity. Obta aining her Ph h. she s had the oportunity o of working w in di ifferent Chem mistry Groups aroun the Wo orld. R. in the sa ame Universit ty in 2002. Ramírez-Cre escencio ACKNO OWLEDGME ENTS Financial support s for th his research by PAPIIT IN101308 I and d PUNTA is gratefully ac cknowledge ed. During D her Ph. ABOUT THE AUTH HORS Rocío Red dón was born in Mexico City C in 1969. J. N. . Garcí ía-Peña and F. Cr raig Jensen fr rom 1998 to 2001. In Chemistry at th C he Universida ad Nacional Autónoma A de México. and in USA U at Hawa aii University with Prof. in 1997 in i England in Essex Univer rsity and in 19 998 in Oxfor rd University with Prof. D. CCADET” in the Univers sidad Naciona al Autónoma de d México. studies. In 1993 she obtained her r B. with Prof. . Dilworth h. Finally y she obtained d a Post-doct toral position in the “Labo oratorio de M Materiales y Nanotecnología a.28 8 Rocío Redón n. in 1998 in n Spain. G. w where she actua ally works on the synthesis and character rization of nan nocomposites dendrimerno oble metal NP Ps and their ca atalytic applica ations. D. c) R. Gao. Sep 23-2 28. 29 2003 471-475 2003. L. J. Commun. P. She obtained d her B.Sc. Po oddenezhnyi. A. to obtain he er M. M. Redón in nan nostructured materials m appli ied to catalysis. J. Cec cilio. R. L. D M. B Nanot technol. W Ind. M. in n 1984 and studied s chemistry at the U Universidad Nacional Autón noma de Méx xico. A-Ge en. Mu urray. 8 2006 421-428. Ma ater. Mate er. W. C. Borisenk ko. S. M. Tewink kel. W. 2nd All l Russian Con nference on C and d Nanotechnology. V. Millot. Bogatyrev. T Mexico. H. Boik ko. N L. . U Appl. Ch hang. M. Pighin ni. N. 177403. Chen. Biomed. Phys. [8 8] E. S. A. H L. Lop pez. b) O. 5 2005 1199-12 202. A. Boatner. Wei. Q Y. in 1982. 48 8 2003 602-6 606. . Re es. Liu J. Catal. Uematsu. J. Chem. C. [1 10] L.Sc. D. Zheludkevich. Sasir rekha. Rev. Chen. G. L. García G Peña was w born in Toluca. L. She is cu urrently worki ing with Prof. de egree in chem mistry from th he Universida ad Nacional Autónoma A de México in 20 008. Lam maka. V. México. A. 8 U. I. Perla. F. D. [7 7] a) R. 93 2004 2 Art No. T. N. N Ichikuni. Y. . 27 2002 132 27-1329. 60 2006 2 18161822. H. Te ech. 1 200 05 297-305. Yasaka au. Mikheeva. Rus ssia. 1 2006 92-98. 8 1996 2047-2055. H. N. Phys. T. Ha aglund. Lett t. Aymes. C. degre ee in chemistr ry. T. [4 4] S. A. Q. Lett. Haglu und. Kwak. W. Nano Lett. 246 2003 87-95. B. V. He is cu urrently comp pleting his Ma aster thesis on interactions of o iridium nan noparticles wit th dendritic sp pecies. [5 5] V. Schub bert. A. Netting. E. S. REF FERENCES S [1 1] [2 2] [3 3] L. Lett. N. Lo opez. S. M. Nanoelec ctron. His und dergraduate re esearch was done d in the gr roup of Prof. F. Q. I Sidorov. L. Wang. Feldma an. Glass Phys s. Gao. . En ng. Rocío R Redón concerning fr ree-solvent syn nthesis of irid dium nanoparti icles. 45 2006 4927-493 35. D. R. M. 2002. Ruan. C. F. P. Webster. Z K. T. Chem. L A. N. E. Sav viot. St Pe etersburg.M Metallic Nanop particles Nanocomposites 29 Nidia G. Surface Chemistry [9 9] J. [6 6] Z. Feld dman. She expects to graduate in i 2010. Mon ntemor. M. Ferreir ra Electrochem m. Odom. Sato. Haynes. Henzie e. Lamber Chem. Fan. Fermín Ra amírez was born in Puebla a. Alekseenko. Optoe. Shimazu. Opt. 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The latter impart solubility and stability to the metal complex and can be used to tune the selectivity of a particular catalyst towards the synthesis of a particular desirable product. Inc. on the other hand are usually complexes. Catalysts speed up chemical reactions but can be recovered unchanged at the end of the reaction. Traditionally. Within this field. They can also direct the reaction towards a specific product and allow reactions to be carried out at lower temperatures and pressures with higher selectivity towards the desired product. Oxidation catalysis is a quite important transformation in both industrial and academic aspects. holding M=O moieties. the active site at which the substrate binds can be constrained in such a way that only one of a large number of possible products can be produced. Homogeneous catalysts. several industrial processes such as ammoxidation of propene to acrylonitrile. the coordination * Corresponding author: Phone: +351 217 500 876. This is a principle that is pursued with increasing emphasis and dedication leading to far more specific and cleaner processes. as molybdenum is highly available to biological systems. Chapter 2 RECENT EVOLUTION OF OXIDATION CATALYSIS BY MO COMPLEXES Carla D.ul. By varying size. olefin epoxidation (ARCO and Halcon processes). with the metal center lying in high oxidation state. which rely on Mo are one of the most important. oxidation catalysts are based on metal oxides. Poehler ISBN: 978-1-61122-894-6 © 2011 Nova Science Publishers. ranging from a variety of available metal centered systems.pt . Fax: +351 217 500 088. E-mail: cmnunes@fc. C8. catalysts. which consist of a metal centre surrounded by a set of organic ligands. Furthermore. and olefin metathesis reactions are carried out over molybdenum catalysts. Inclusively. Vaz Centro de Química e Bioquímica. Portugal ABSTRACT For 80% of all compounds produced in chemical and pharmaceutical industry at least one catalytic step is essential during their synthesis.In: Homogeneous Catalysts Editor: Andrew C. Campo Grande. Departamento de Química e Bioquímica Faculdade de Ciências da Universidade de Lisboa Ed. 44 Carla D. Nunes and Pedro D. Vaz chemistry of MoVI has stimulated considerable interest in view of its biochemical relevance, and many MoVI complexes have been studied as models of molybdoenzymes. In recent years the development of new approaches to prepare new and stable catalyst has turned to low oxidation state MoII organometallic complexes. These precatalysts proved to be quite adequate to the purpose by being highly active and selective in the epoxidation of olefins and in oxidation of other substrates. Additionally, such precatalyst complexes are more stable towards air and moisture which allows easier handling. This chapter lights up some recent advances on olefin oxidation chemistry based on Mo catalysts with special focus on the development of new approaches to achieve active catalysts. INTRODUCTION The significant enzymatic role of molybdenum in biochemical reactions [1–3] specially in the oxidation of aldehydes, purines and sulfides [4] induced chemists to use molybdenum complexes as biomimetic catalysts in the oxygenation of organic compounds [5,6]. Under such auspices, MoVI dioxo-complexes have been extremely investigated [7–9] particularly with respect to the catalytic role of transferase enzymes like nitrate reductase in which their active sites consist of a cis molybdenum dioxo moiety [10,11]. The ability of molybdenum to form stable complexes with oxygen-, nitrogen-, and sulfur-containing ligands led to development of molybdenum Schiff base complexes which are efficient catalysts in both homogeneous and heterogeneous reactions [12–15]. The activity of such complexes varies markedly with the type of ligands and coordination sites [16]. Molybdenum-catalyzed olefin epoxidation has received interest from both academic and industrial research laboratories because epoxides are important building blocks in organic synthesis and polymer science [17–20]. Although numerous procedures have been developed [21-24], there is still a need for the development of new catalysts that may uncover a more detailed understanding of oxidation pathways and inform the design of more efficient catalytic systems. Since the first example of a molybdenum oxo complex catalyzing the epoxidation of alkenes with peroxides such as organic hydroperoxides and hydrogen peroxide [25], a variety of different complexes have been developed [26–41]. Despite this, molybdenum catalysts are also suitable for many other oxidation reaction types. Oxidation of alcohols to aldehydes and ketones is one of the most important transformations in organic synthesis [42–44]. In particular, the oxidation of primary alcohols to aldehydes is important since they find wide applications as intermediates in fine chemicals particularly for perfume industry [45–48]. Traditionally, the oxidation of alcohols is carried out using stoichiometric inorganic oxidants such as permanganate, bromate, or chromate based reagents which generates large amount of heavy metal waste [49-52]. Several transition metal-based homogeneous systems such as palladium [53–64], ruthenium [65–68], manganese [69,70], tungsten [71], rhenium [72], copper [73,74], and iron [75,76] have also been reported. However, mixtures of the organic substrates, products, solvents, and molecular oxygen are well known for being explosion hazards in many cases. In addition, catalytic oxidation of amines is also a major functional transformation in organic synthesis [42–46]. Amongst the possible amine oxidation products (hydroxyl, nitroso, nitro, azo and azoxy), aromatic nitroso compounds are utilized extensively as chemical feedstocks for a wide range Recent Evolution of Oxidation Catalysis by Mo Complexes 45 of useful materials such as dyes, pharmaceuticals, perfumes and plastics [47,48]. As a drawback, amine oxidation poses problems due to non-regioselectivity or over-oxidation of amines and competitive oxidation of substrates. Within this context, MoVI complexes have proved also as adequate catalysts for such transformations being explored in several works given its functional as well as structural similarity with molybdo-enzymes catalyzing a variety of oxidation reactions [77–80]. Oxidation reactions using Mo complexes occur in the presence of terminal oxidants, Chart 1, such as hydrogen peroxide (H2O2), or organic hydroperoxides, such as urea hydrogen peroxide complex, tert-butyl hydroperoxide, ethylbenzene hydroperoxide, cumyl hydroperoxide and trityl hydroperoxide. Chart 1 Hydrogen peroxide 1 Urea·H2O2 complex 2 tert-Butyl hydroperoxide 3 Ethylbenzene hydroperoxide 4 Cumyl hydroperoxide 5 Trityl hydroperoxide 6 From this library of peroxide oxidants it has been found in recent years that H2O2 is the least competent oxidation agent concerning olefin epoxidation. In this way olefin epoxidation reactions have centered mainly on the use of the organic hydroperoxides. When these are used, olefin epoxidation proceeds via a Lewis acid catalyzed process. This is a class of reactions known as heterolytic reactions involving a two-electron transfer process. In this process the catalytic center does not undergo a change in its oxidation state. It occurs since the electron-transfer steps involving the metal are concerted and accordingly there is no valence net change in the metal. The key role of the metal is then to activate the organic peroxide (ROOH) in such a way that an O atom from it may be transferred to the olefin. OXIDATIONS WITH [MOVIO2]2+ COMPLEXES AS CATALYSTS The majority of studies dealing with catalytic applications using high-oxidation state Mo complexes has traditionally relied on the use of simple complexes centered on the tetrahedral MoO2X2 (X = Cl, Br) core shown in Chart 2. VI 46 Carla D. Nunes and Pedro D. Vaz Chart 2 7, 8 Particular interest in MoVI-oxo complexes arose in the late 1960s when ARCO and Halcon presented patents on the olefin epoxidation catalyzed by MoVI compounds in homogeneous phase [81,82]. In the following years different mechanisms were suggested to explain the reactivity of these complexes. The debate as to which of the two main proposed mechanisms is more accurate, the one favored by Mimoun et al. [83] or the one suggested by Sharpless et al. [84] has not been settled to date, despite the fact that several theoretical and mechanistic studies have been presented [85]. It has been generally agreed, however, that formation of a MoVI alkyl peroxide occurs followed by transfer of the distal oxygen atom of the alkyl peroxide rather than an oxo ligand [86]. The industrial ARCO and Halcon process employs tert-butyl hydroperoxide (tbhp) as oxidizing agent. Despite the fact that H2O2 is a more environmentally friendly oxidant (the only byproduct formed is H2O), tbhp has other advantages that still make it the preferred oxidizing agent in industrial processes [87]. A kinetic model, proposed by the groups of Kühn and Gonçalves [88], was built up for a homogeneous batch reactor based on a simplified mechanism involving three steps: (i) reversible coordination of tbhp to the starting MoVI complex to give a MoVI alkylperoxide; (ii) irreversible oxidation of cyclooctene to cyclooctene oxide by the species formed in step 1, with formation of the starting complex and tert-butyl alcohol; (iii) reversible coordination of tert-butyl alcohol to the starting complex. This model is consistent with the observed kinetics. The first step in this reaction mechanism was characterized in more detail by studying the kinetics of the reaction of the starting complexes with tbhp in the absence of any reductant by UV/Vis spectroscopy. Rate constants, equilibrium constants, and activation parameters were determined. All ΔS‡ values were negative and therefore support an associative mechanism in which a seven-coordinate intermediate is formed. The results also suggest that the first step is not always the rate-limiting step of cyclooctene epoxidation with these complexes. DFT calculations later on have confirmed such findings for such mechanism proposal [89]. This mechanism, proceeds through coordination of the hydroperoxide to the metal center, Scheme 1. Coordination proceeds by means of the distal oxygen atom of the peroxide, rather than the proximal one. The very next step is the H-atom transfer to one of the oxo ligands of the metal center. It then starts with a hydrogen transfer from the peroxide to one of the terminal Mo=O oxygen atoms and the remaining t-BuOO− anion binds as a seventh ligand, forming a fivemembered ring held together by a hydrogen bond. In the second step, a concerted approach of the olefin to the Mo–Od (Od = distal) bond gives rise to an intermediate containing a sevenmembered Mo–C–C–Od–Op(t-Bu)···H–O–Mo ring (Op = proximal). In the final step, decomposition of the intermediate leads to the starting complex, alcohol and the desired epoxide. The activation energy for the addition of the olefin (second step) is the highest one, in agreement with available kinetic studies showing that the catalyst formation is not always a Recent Evolution of Oxidation Catalysis by Mo Complexes 47 rate-limiting step. There is also evidence that the resulting alcohol by-product (t-BuOH) can react with the starting complex, competing with t-BuOOH and hence leading to the progressive catalyst poisoning, which has been observed experimentally. Scheme 1. Proposed reaction mechanism for t-BuOOH activation and olefin epoxidation at the NOX face of octahedral [Mo2O2X2L2] (X = Cl, Br, Me) complexes. The metal is hidden for clarity. Op and Od stand for proximal and distal O atoms in peroxide. From the continuing research developed using such catalysts, much of the work has centered on ligand design. Many works have been devoted to exploring the chemistry of a large family of complexes of formula MoO2X2(N,N’) or MoO2(N,O)2 where N,N’ and N,O are bidentate ligands and X = Cl, Br, alkyl [89–101]. The reactivity and selectivity of such complexes is largely dictated by the bidentate ligands and recently a high asymmetric induction was achieved for the first time on this kind of systems [102]. The simpler MoO2X2 or MoO2X2L2 derivatives (L = labile ligand) have been less studied in this regard [103–105]. Starting from the late 70’s and early 80’s decades of the XXth century, a rising interest in stable organometallic complexes arose during the development of models for reactive intermediates for the nitrogenase enzyme [106–108]. For this reason, reactions of MoO2X2(bpy) (X = Cl, Br ; bpy = 2,2’-bipyridine) precursors with different Grignard reagents were thoroughly explored by Schrauzer and co-workers. The first isolated compounds were of the type MoO2BrR(bpy) and being synthesized by reacting MoO2Br2 (bpy) with different organomagnesium halides in thf. Some of the MoO2BrR(bpy) complexes were isolated [R = Me [106], Et [106], CH=CH2 [107]], while others were only generated in solution [R = Pr, i-Pr, t-Bu, CH2C(CH3)3] [108]. Complexes with Me and Et react back with Br2 to yield MoO2Br2(bpy) and CH3Br or C2H5Br, respectively. A modification of the synthetic method used for MoO2BrR(bpy) afforded the preparation of several complexes of composition MoO2R2(bpy), as evidenced in Chart 3. 48 Carla D. Nunes and Pedro D. Vaz Chart 3 The first compound of this type obtained, MoO2Me2(bpy) [109], was synthesized by reacting MoO2Br2(bpy) with methylmagnesium chloride in thf. Several other complexes, namely, ethyl [112], propyl [112], butyl [112], neopentyl [110], cyclopentyl [112], cyclohexyl [112], benzyl [111], several aryl [113–116], and organosilicon derivatives [117], followed in the following years using different Grignard reagents. From this set of complexes, MoO2Me2(bpy) exhibits a high thermal stability (melting point = 503 K) and is stable under air. The decomposition temperatures were found to be related to the stability of the Mo-C bond. Decomposition was observed to occur on prolonged heating under basic or acidic conditions in solution. The most temperature sensitive are those complexes with hydrogens in β-position like the diethyl derivative or those where steric effects cause an additional Mo-C bond labilization, as found in the c-C6H11 derivative. In 1991 the first examples of MoO2R2L2 complexes were reported, where L2 was not bpy but 4,4’-dimethyl-2,2’-dipyridyl (Me2-bpy), conferring a higher solubility to the synthesized compounds [118]. The MoVI compounds MoO2R2L2 [L2 = Me2–bpy; R = CH2–CHMe2 (9), CH2–CMe3 (10), (CH2)4CH=CH2 (11), CH2Ph (12), CH2C6H4Me-p (13), and CH2CMe2Ph (14), Chart 4, were prepared by reaction of the corresponding Grignard reagents with MoO2Br2L2, followed by aerobic oxidation of the resulting reaction mixture. Chart 4 9 12 10 13 11 14 The decomposition reactions of these compounds were studied in very detail by Vetter and Sen [118]. The complexes were found to decompose in solution under inert gas atmosphere at varying rates. The course or rates of the reaction were found not to be influenced by the nature of the solvent in use. As the decomposition evolves, insoluble Recent Evolution of Oxidation Catalysis by Mo Complexes 49 molybdenum oxides are formed and in solution quantitative amounts of hydrocarbons can also be detected. Anaerobic decomposition associated with a given complex is a sensitive function of the hydrocarbyl group R. If β-hydrogens are present on R, equal amounts of alkane and alkene are formed through a β-hydrogen abstraction pathway. When β-hydrogens are absent from R, the predominant product is the free radical R· formed by Mo-R homolysis. Other complexes of the type MoO2R2L2 (R = CH3, C2H5; L = bidentate Lewis base ligand) were reported by the research groups of Gonçalves, Kühn, and Romão during the past decade [34,94,95,119,120]. A wide range of compounds was synthesized, bearing a variety of bidentate ligands of the type 1,4-diazabutadiene (R-dab), with different R groups, phenanthroline, and substituted bypiridines, Chart 5. Chart 5 Besides providing access to more soluble complexes, which are better amenable to reactivity and spectroscopic characterization than the modestly soluble MoO2R2(bpy) derivatives, the different stereochemical and electronic characteristics of these ligands impart distinct reactivities to the MoO2R2 core. Such complexes were obtained by alkylation of MoO2X2L2 (X = Cl, Br) with the appropriate Grignard reagent [34,94,119,120]. The catalytic properties of MoO2X2L2 (X = Cl, Br) and MoO2R2L2 [R = CH3, C2H5; L = 1,4-diazabutadiene (R-dab), with different R groups, phenanthroline, or substituted bypiridines] (Chart 5) have been recently studied in detail by several research groups [34,94,95,119,120]. The complexes were found to be active for the epoxidation of olefins using tert-butylhydroperoxide as oxidant at moderate temperatures (328 K). However, when H2O2 was employed as the oxidant, no epoxidation products could be obtained, Scheme 2. The catalytic performance of such complexes is resumed in Table 1 showing results of olefin epoxidation using both MoO2X2L2 (X = Cl, Br) and MoO2R2L2 (R = CH3, C2H5; L = N,N’-bidentate ligands) complexes as catalysts. Scheme 2. Efficient and inefficient olefin epoxidation using tbhp and H2O2, in the presence of MoVI catalysts. 50 Carla D. Nunes and Pedro D. Vaz Table 1. Catalytic performances of catalysts based on MoO2X2L complexes (X = Cl, Br, CH3; L = bidentate Lewis base ligand) in cyclooctene epoxidation at 328 K and after 24 h reaction [94]. X Cl 15 Br 16 73 L Conversion % 89 57 17 65 18 27 19 24 20 CH3 21 35 22 92 23 35 89 24 Recent Evolution of Oxidation Catalysis by Mo Complexes 51 60 25 29 26 72 27 48 28 40 29 In most cases, the overall yield obtained after 4 h is relatively low (between 5 and 60%), but increasing greatly up to 24h reaction time. However, over a 24 h period yields proved to be strongly dependent on L and R ligand type used. Electron-attracting ligands L lead to more active compounds, rendering the electron deficient molybdenum center. Steric effects of the ligands also seem to play an important role on the catalytic activity. Ligands, which create more steric hindrance near the metal center, usually decrease the catalytic performance of complexes. Increasing both reaction time and temperature leads to a significant increase in the product yield in all examined cases. However, at ca. 363 K further increase in product yield is hampered by catalyst decomposition. This is most evident with the organometallic MoO2R2L2 (R = CH3, C2H5; L = N,N’-bidentate ligands) derivatives. It is also remarkable that during the catalytic cycle loss of the R group as methane, ethane, or methanol by a potential M–C bond breaking does not play an important role. The use of MoO2X0-2L1,2 (X = halogen; L = mono-, bi- or tridentate ligands) complexes have also been thoroughly studied as evidenced in Table 2. In fact variation of the coordination sphere around the metal center (0-2 halogen ligands and 1 or 2 Lewis base ligands) were found to be crucial based on the reported results. From the results shown in Table 2, it is possible to observe that terminal olefins are generally more resistance to oxidation and that the use of H2O2 does not favor the reaction. This is quite clear in the epoxidation of cyclooctene where reactions do occur to completeness in the presence of tbhp while with H2O2 they do not. Table 2. Catalytic Performance of MoO2X0-2L1,2 (X = halogen; L = mono-, bi- or tridentate ligands) complexes in olefin epoxidation. X L Olefin Oxidant Conversion % Epoxide sel. % Ref. — 30 O2 96 0 121 O2 O2 86 95 85 81 tbhp 31 tbhp tbhp tbhp 73 46 100 96 100 100 100 100 122 tbhp 70 100 tbhp 96 100 tbhp 46 65 tbhp 48 68 tbhp tbhp tbhp F H2O2 40 77 45 99 100 91 100 100 123 32 Cl 33 tbhp 100 100 124 tbhp 100 59 H2O2 34 68 100 125 tbhp 35 H2O2 36 126 80 100 127 tbhp 37 96 100 128 . X L Olefin Oxidant Conversion % 100 Epoxide sel. % 100 Ref.Table 2 (Continued). 39) (R = Cl. Asymmetric catalysis is a particularly elegant and efficient method to achieve the introduction of such functional groups into larger organic compounds [132]. From several RTILs tested in recycling catalytic experiments with complex 39 the best results were observed for the system using [bmim]NTf2. Chiral epoxidations are currently of high interest for the synthesis of non-racemic chiral intermediates in the pharmaceutical and chemical industries to generate such optically pure products [87]. Development of chiral active pharmaceutical ingredients (APIs). The catalytic properties of MoO2R2(Me-p-tolyl-dab)2 (38. is of major relevance since it is recognized that enantiomers of a chiral compound can have dramatically different biological activities. When developing catalysts for a given reaction one must bear in mind not only high activity but more important. The need of enantiomerically pure chiral compounds faces a continuous rise. Such results led to the belief that some chiral derivatives of these complexes might be applied equally efficiently as chiral . in some case with severe adverse effects [130].4-p-tolyl-1. either chlorinated or an adequate RTIL. entry 8.3-butadiene) were assessed for olefin epoxidation under not only the previously applied conditions (tbhp as oxidant. Enantiopure complexes are used mainly in pharmaceuticals but not limited to. Chart 6 38. and specialty materials. The application of RTILs also enabled the catalyst recycling. In a quest for more efficient and selective catalysts some works have devoted to the development of MoVI catalysts with chiral ligands to yield enantiopure compounds. CH3 . 39 The authors reported that this complex presents excellent selectivity toward the epoxide formation relatively high activity under solventless conditions or with additional solvent. In fact if a catalytic system is not selective then it is of no real use.4-diaza-2. 328 K) but also using as alternative solvent several RTILs. as evidenced in Table 3. for example. as well as in other sectors such as flavor and aroma chemicals.Recent Evolution of Oxidation Catalysis by Mo Complexes 55 Room temperature ionic liquids (RTILs) have also been used as alternative solvents. selectivity. Chiral epoxides. From the results discussed above in this chapter. it was shown that non-chiral MoVI (organo)complexes could successfully yield racemic epoxides. Chart 6 and Table 3 [129]. Me-p-tolyl-dab = 1. This is powered by the increasing number of legal regulations and health concerns as well as the need for industrial efficient processes. agricultural chemicals. are a key structural unit present in many biologically active compounds as well as in important natural products [131].3-dimethyl-1. in particular. 39) for olefin epoxidation in the presence of regular solvents or RTILs [129]. Starting in the 70’s decade of the XXth century.56 Carla D. methyl pyrolinols and diisopropyl tartrates as ligand species [134]. Catalytic performance of MoO2R2(Me-p-tolyl-dab)2 (R = Cl.82]. were found in the class of 2’-pyridyl alcohols. % 100 100 100 100 100 100 100 96 [bmim]NTf2 (R = H) [bdmim]NTf2 (R = CH3) 100 53 14 100 100 [C5O2mim]PF6 92 [(d-h)2dmg]PF6 100 . R Cl Solvent / RTIL None Dichloroethane Conversion % 100 94 73 CH3 [bmim]PF6 (R = nBu) None Dichloroethane 100 100 90 [bmim]PF6 (R = nBu) [C8mim]PF6 (R = nOct) 94 Epoxide sel. have found application in chiral epoxidation reactions. MoVI complexes with different types of chiral ligands.136] and from which MoO2L2 (L2 = 2’-pyridyl alcoholate) type complexes that were active as catalysts for epoxidation. Chiral ligands which were easy to make and stable in oxidation reaction conditions were also searched for. among which diisopropyltartrates. lactamides and several other hydroxyacid amides. could be prepared. The application of chiral MoVI complexes in olefin epoxidations was a spin-off of the application of homogeneous MoVI catalysts in the Halcon and Arco processes [81. CH3) complexes (38. Some examples accounted with the use of N-alkyl ephedrines [133]. Ligands that would also allow the possibility of varying steric characteristics easily through simple substitutions. Nunes and Pedro D. which were known to be easily accessible [135. Table 3. Vaz catalysts. In that case the oxazoline ligands were bound to the metal by a covalent Mo–O bond in contrast to previous reports. Kühn and coworkers [98] also synthesized MoO2Cl2L (L = oxime). 43. 44 [96].and . Chart 7. Chart 7 40 41 42 The complexes were examined for their catalytic activity and good conversions. with the bulkier norbornane ligands leading to the highest optical inductions. toluene as solvent and tbhp as oxidant. was obtained. being observed. conversions from 25 to 30% were reached within 18 h at 308 K. Enantioselectivities were more dependent on the ligands being found to range between 4 and 26%.8-diol) and MoO2Cl(thf)L (L = 8-phenylthioneo. Herrmann et al. Gonçalves and coworkers [139] reported MoVI dioxo complexes holding coordinated pyridyl alcoholate ligands and used in olefin epoxidation. Using tertbutylhydroperoxide (tbhp) as oxidant at 328 K. Chart 8 43 44 Using styrene as substrate. to form enantiomerically pure 2‘-pyridinyl alcoholates which were subsequently applied as chiral ligands in MoVI complexes. Teruel and colleagues [92] also applied chiral oxazoline ligands attached to MoO2 cores. 2%). In 2000. 20% with an ee of 25% using 1-hexene as substrate. lying in the range from 4 to 6%. for the epoxidation of trans-β-methylstyrene. A conversion of ca. in 2001. Selectivity was below 50% and ee’s were still negligible (ca. in the range of 70%. Chart 8. Mono-substituted complexes were more active than those with two chiral ligands. [MoO2(thf)2L] (L = cis-p-menthane-3. Later on. up to 86% conversion was achieved although ee’s were very low. Another class of suitable C2-symmetric bis(oxazolines) chiral chelating ligands were developed in parallel [96] by Romão et al. Chart 8. [138] made use of chiral precursors.Recent Evolution of Oxidation Catalysis by Mo Complexes 57 In 1999 Bellemin-Caponnaz and others demonstrated this by applying the ligand 2[(−)menthol-pyridine] to such a complex [137]. Vaz isoneomenthol) complexes. When esterification was used to protect the –OH group in the sugar ligand tridentate coordination of the ligand took place due to Lewis acid catalyzed deacetylation. and already discussed in this chapter. Nunes and Pedro D. to prepare complexes of general formula MoO2L (L = sugar). In the case of cis-β-methylstyrene ee’s of up to 30% were achieved. ee’s of up to 23% and conversions up to 58% (temperatures 323– 343 K) were reached [142]. tbhp as oxidizing agent and toluene as solvent (328 K). The observed ee’s were on an average low. with 24% in the best case using complex (45). Chart 10. Chart 10 46. which made possible to explain the good activity and low enantioselectivity of the MoVI complexes with coordinated oxazoline ligands [143]. in 2004. at 72% conversion.89]. When tbhp or cumyl hydroperoxide (chp) were used as oxidants and trans-βmethylstyrene as substrate. Following also their previous work [92]. Chart 9 45 The first sugar ligands were attached to [MoO2]2+ moiety by Rao and coworkers [140] in 2001. Conversions were found to reach 63–82% obtained with the cisβ-methylstyrene as substrate. They proposed a reaction mechanism for olefin epoxidation catalyzed by a seven-coordinate molybdenum species with hemilabile ligands as it was later on confirmed by kinetic and theoretical studies [88. Turnover frequency (TOF) was high (13000 h-1 in the best case) when cyclooctene was the substrate although velocity of reaction slowed down with increasing time. In 2004 Herrmann published [142] further results in continuation of previous work published in 2000 [138].58 Carla D. A number of chiral 2’-pyridinyl alcohols were used as ligands for the MoO2 core. published further research. Chart 9. 47 These were applied in olefin epoxidation by Kühn et al. [141]. In the same year. Teruel et al. Singh and . Shi and coworkers [146] used both mono and tetradentate compounds for the asymmetric olefin epoxidation of cis-1-propenylphosphonic acid with 30% aqueous hydrogen peroxide affording (1R.Recent Evolution of Oxidation Catalysis by Mo Complexes 59 coworkers [144] also reported a chiral MoVI compound with bidentate oxazoline ligands. the systems presented in Table 4 using the pyridine 2’-alcoholate ligands reported by Hamann [148] were found to be quite original since they relied on the use of chiral hydroperoxides instead of the use of chirality in the ligands. 12%). additionally it was found that an excellent regiospecificity was also achieved. in recent years. Table 5.2R)-N. Chart 11.4-diazabutenes of the type R–N=C(Ph)–C(Ph)=N–R. In parallel studies some attention has been devoted. Reactions were found to proceed with high retention of configuration and high selectivity to the epoxide. This reaction is strongly influenced by ligands. 44. For example in a complex with a tetradentate salen ligand. . solvents as well as reaction temperatures. cumyl hydroperoxide (chp) or trityl hydroperoxide (thp) and chiral bis-hydroxamic acid (bha) derivatives as ligands [149-151]. Gonçalves and coworkers also prepared chiral 1. Kühn et al. Chart 11 48 In addition to these results. (1R. The outcome was the synthesis of epoxides with good ee’s and additionally.2)-epoxypropyl phosphonic acid. In fact. see Chart 8. a few others not discussed within the text are screened in Table 4. used a tetradentate chiral Schiff base. 65%) could only be achieved at low conversions (ca.2S)-(−)-(1. The resulting complexes were applied as effective catalysts for epoxidation using cis. better ee’s were obtained in noncoordinating solvents such as methylene chloride than in a solvent like ethanol. obtaining ee’s up to 26% with cis-βmethylstyrene [145]. these being obtained from a linear terminal olefin which is usually seen as unactivated. stressing the relevance and difficulties of assessing enantiopure epoxides. active in the epoxidation of styrene.4-pentanedionate) in the epoxidation of olefins as well as in sulfide oxidation using tert-butyl hydroperoxide (tbhp). only for cis-β-methylstyrene though. An ee of 69% for a MoVI complex coordinated to ligand 48 was observed at 30% conversion after 24 h reaction time.2-diamine and hexa-coordinate MoVI complexes [100]. In this case high 77% ee at room temperature was obtained (at 24% conversion). In olefin epoxidation experiments all oxidation products were achieved in high enantiomeric excess (ee) and.and trans-β-methylstyrene by tert-butylchloroperoxide. to the use of [MoO2(acac)2] (acac = 2. Increasing the reaction temperature increased the epoxide yields but good enantiomeric excesses (ca.N’-dibenzylidenecyclohexane-1. reaching yields of up to 70%. % ee % Ref. Complex Olefin Oxidant Conversion % Epoxide Sel.Table 4. tbhp 92 100 <5 147 49 7 36 <5 <5 AcO OAc O OOH 50 100 100 30 100 100 50 148 100 100 20 . Chiral epoxidation of olefins with MoO2L2 complexes and organic hydroperoxides. 100 100 28 100 100 53 100 100 40 100 100 38 100 100 34 . alcohols. Another important aspect of such Mo–bha catalysts is that it selectively oxidizes the most electron rich alkene in the presence of multiple double bonds (entries 14.3epoxysqualene with good enantioselectivity (69% ee). Scheme 3. last entry). for the rapid preparation of enantiopure sulfoxides. has garnered extensive attention from the synthetic community. Although a number of methods for assessing high enantioselectivity during sulfide oxidation have emerged in recent years [152165]. On the other hand if that ratio rises to 5 sulfones are selectively obtained. Asymmetric sulfide oxidation. 17). Nunes and Pedro D. in the presence of a MoVI dioxo complex. Reaction conditions for asymmetric sulfide oxidation using Mo-bha catalytic system. To delight of the authors. arenes. It was noteworthy since synthesis of 2. phosphines and sulfides [170–174]. low enantioselectivity and restrictive structural requirements are still serious obstacles for such transformation [152-156]. This is a fine example of selectivity tuning based on variation of reaction conditions. Of particular value are those compounds which contain chiral sulfoxides. as evidenced in Scheme 4. In a different approach. Sheikshoaie [166] has reported selective oxidation of sulfides to sulfoxides or sulfones by varying the quantity of urea hydroperoxide (uhp) used as oxidant.3-epoxysqualene often requires multiple steps. In this way the authors have found that the Mo-bha system selectively oxidizes a single optical isomer with resulting resolution enhancement which is sometime so difficult to achieve [150]. A variety of synthesis of peroxocomplexes of various metals are known [167–169] to catalyze the oxidation of olefins. was subjected to similar reaction conditions. OXIDATIONS WITH [MOVIO(O2)2]2+ COMPLEXES AS CATALYSTS Transition metal peroxo and peroxy complexes have played for some time now an important role in the epoxidation of alkene substrates to their respective epoxide products. entry 16. Table 6 evidences the most relevant achievements stressing catalysts capability to perform such transformations which are relevant in organic synthesis. . Additionally in that work [150] the authors have also reported kinetic resolution for formation of sulfides to sulfones. Vaz From Table 5 it is possible to conclude that trisubstituted and terminal alkenes also provided good selectivity (entries 8−13). 15. The Yamamoto group has reported also the use of the Mo-bha system for asymmetric sulfide oxidation. squalene (Table 5.62 Carla D. In this way if uhp/sulfide ratio is 1 only sulfoxides are obtained. phenols. an important biogenetic precursor of steroids and polycyclic terpenoids. the Mo-bha complex in the presence of 1 equiv of chp selectively provided 2. Encouraged by the selectivity observed for myrcene oxidation (Table 5. according to the reaction shown in Scheme 3. a structural class widely utilized in both the pharmaceutical industry and academia [152-156]. Chiral epoxidation of olefins using MoO2(acac)2 complex with bha ligands [149].R) chp 77 64 (R.Table 5. Ligand Olefin Oxidant Epoxide Yield % ee % tbhp 51 20 28 tbhp 52 chp thp 15 42 72 27 66 96 chp 53 tbhp 82 87 92 96 (R.S) . S) tbhp 41 81(S.S) tbhp chp tbhp chp 47 91 13 33 33 (E/Z) 75 (R) 43 69 .Table 5 (Continued). thp 95 85 (R) chp 84 82 (R) O chp tbhp 95 77 85 (R) 43 (R) Ph chp 89 50 (R. and quite a number of studies have been conducted [22.188. thp.27. 41 h 298 K.189]. Similarly to that described previously in this chapter. in 1969 [190] and the earlier development of the Arco [81] and Halcon industrial processes [82]. In this regard MoVI complexes are an important class of oxidants for this type of reaction.Recent Evolution of Oxidation Catalysis by Mo Complexes 65 Table 6. Sulfide Reaction time / h 16 Yield / % 81 ee (%). . CH2Cl2 Racemic 273 K. 24 h 45 (75% ee) 46 (68% ee) 55 54 Scheme 4. The catalytic activity of peroxometal complexes is influenced by the type of metal atom. the number of peroxo ligands attached to the catalyst and the nature of the remaining ligands in the coordination sphere [175–187]. Asymmetric sulfide oxidation using MoO2(acac)2 complex with bha ligands and thp as oxidant [150]. much of the impetus for this research has in many ways been due to the early contributions by Mimoun et al. Kinetic resolution of sulfoxides during sulfoxide to sulfone oxidation. config 79 (S) 20 75 81 (S) 19 76 75 (S) 18 81 82 (S) 24 66 62 (R) 17 82 86 (S) 19 83 72 (S) O O N OH N OH C(4-iPrPh)3 S O S + : : (PhiPr-4)3C O O S MoO2(acac)2 . In the case of bulkier ligands. Kagan et al. Chart 12 54 . Chart 12. dmf. is well known [191]. This core. far lesser progress has been made over the years in obtaining highly stereoselective versions of this reaction using oxoperoxo MoVI chiral complexes at either the stoichiometric or catalytic level. When these are less bulky. is still an open challenge. Nunes and Pedro D. which gives more stable compounds than its diperoxo analogue. [212] reported another catalytic version of this reaction. in all cases. converting itself into a [MoO(O2)]2+ core. for olefin epoxidation using molecular oxygen [190]. py).2. organic ligands are generally used to complete the coordination sphere. yielding chiral epoxides.66 Carla D. In the late 1970’s Schurig et al. The reason advanced for such result was that an enantiofacial discrimination of the olefins and kinetic resolution leading to enrichment of the enantiomers was not likely [212]. MoVI-peroxo complexes also catalyze the oxidation of alcohols to carbonyl compounds [201] and amides to hydroxamic acids [202. hmpa. the 7-coordinate complexes obtained are of the type MoO(O2)2L (L = bidentate ligand) [177. with an yield of 70% and ee of up to 34%.203]. it has been shown that the MoO(O2)2 cores with bidentate ligands are useful catalysts in the epoxidation of olefins [196–200]. again for the epoxidation of trans-but-2-ene. namely. The highest ee obtained was only 35%. [MoO(O2)]2+ accommodates the bidentate ligands by forming oxomonoperoxo complexes of the type MoO(O2)L2 (L = bulky bidentate ligand) [193-195]. among which primary and secondary alcohols. [211] reported the preparation of an optically active MoVI-oxodiperoxo complex 55 (Chart 13) and its application in enantioselective epoxidation of trans-but-2-ene. L =H2O. In addition some other achievements in oxidation of several organic substrates with varying functional groups. an important structural motif. but is also a rather reactive species. Vaz In oxoperoxo chemistry of Mo. Conversion to the trans-(1R. The quest for a chiral analogue of the Mimoun oxodiperoxo MoVI type complexes of general formula MoO(O2)2Ln (n = 1. Recently.2R)-but-2-ene oxide was accomplished. showing its effectiveness over a range of olefins which could be enantioselectively epoxidized in the presence of only 10 mol% of 55. which readily performs substrate oxidation. Shortly afterwards. In such complexes. has a high formation tendency. Despite enormous effort that has gone into developing these processes. the oxomonoperoxo core.193–195]. as well as sulfides have also been reported [204–210]. although recognized as most stable [191] and a common motif in oxoperoxomolybdenum [192]. in which two peroxo groups and a doubly bonded oxo ligand create the median MoO(O2)2 plane. In attempts to study the mechanism of oxygen transfer in this epoxidation reaction by Modena and co-workers a series of reactions with chiral MoVI catalysts as chiral tools was carried out to probe its mechanism. (49% ee) and (S)-3methylpent-1-ene with either MoO(O2)2·pla (51% ee for the 2S. [215] also prepared a set of other chiral MoVI-oxodiperoxo complexes based on a series of enantiomerically pure hydroxyamides. MoO(O2)2·pla. such studies were unable to provide clear-cut evidence on the oxygen transfer mechanism from the MoVI-peroxo complex. and (d) the type of chelate ring formed by the ligand with the metal. (S)-piperidine lactamide (pla) (56). A series of stoichiometric epoxidations of prochiral. Besides reactions using complex 55.3S)-2-hydroxy-3-methylpentanoic acid piperidineamide (hmppa) (59). unfortunately.N-dimethyl-(−)-menthylamine-N-oxide.3S diastereomer) or with MoO(O2)2·dmla (55) (51% for the 2S. (S)-2-hydroxy-3-methylbutanoic acid piperidineamide (hmbpa) (58). (2S. 7–9% ee) which contradicted previous findings of Mimoun [213]. Another relevant factor discovered was that enantioselectivity was inversely dependent on the degree of alkyl substitution present in the olefin. (b) the degree of branching of the alkyl substituents. Preferential formation of (R)-alkyloxiranes has been detected. It was also evidenced that certain chiral monodentate ligands. (S)-N. affording the major enantiomer with 36% ee [214]. Schurig et al. as reaction ee decreased in the following order: prop-1-ene > but-1-ene > 3-methylbut1-ene. schematized in Chart 14. can be used to give enantioselective epoxidations (albeit low.3S diastereomer and 49% for the 2R. (S)-N-acetylprolinol (AcPro) (61) and (S)-N-benzoylprolinol (BzPro) (62). like. The best results were obtained using trans-but-2-ene with the complex derived from (S)-piperidinelactamide. The highlight of this work was use of complex 55 in the epoxidation of trans-oct-2-ene under the same conditions as used by Schurig et al. (−)-menthyl-phosphoric triamide and N. (c) presence of an additional stereogenic centre. The chiral hydroxyamide ligands mentioned above with a variety of structural differences were screened with an objective at gaining some insight into the influence of: (a) the size of the amide component.3S diastereomer and 49% for the 2R.3S diastereomer).N-dimethyl3-phenyllactamide (dmpla) (57). (S)3-hydroxybutanoic acid piperidineamide (hbpa) (60).Recent Evolution of Oxidation Catalysis by Mo Complexes Chart 13 67 55 Mimoun then tested some chiral monodentate ligands noticing there was no observable asymmetric induction [213]. chiral racemic and chiral non-racemic olefins were used in a study using the above mentioned complexes. . Still. on the enantioselectivity of the reaction. 68 Carla D. as this property increased in the following order: seven-membered chelate > six-membered chelate > five-membered chelate. epoxidation of trans-but-2-ene with MoO(O2)2·pla and one equivalent of (2S. according to Chart 15. It was suggested that a subsequent kinetic resolution of the oxirane products by a till then unknown Mo-diol catalyst would lead to this enantiomeric enrichment. Vaz Chart 14 56 pla 57 dmpla 58 hmbpa 59 hmppa 60 hbpa 61 AcPro 62 BzPro Since then it has been established that when the steric bulk in the main chain of the ligand was increased depending on the type of amide ligand there was an increase or decrease in the ee. The chelate ring geometry formed between the ligand and the metal was also shown to affect enantioselectivity of oxirane formation. The complexes were obtained from the reaction of chiral phosphinoyl alcohols with MoO(O2)2 being suggested that coordination to the Mo center would occur through the P=O group. It was only in 1999. a decade later. It was also established that the addition of optically pure 1. For instance. Nunes and Pedro D.2-alkanediol additives enhanced ees of the oxirane products.3S)-butanediol yields the corresponding epoxide with 93% ee. Chart 15 63 64 65 66 67 68 69 70 . that Stirling and co-workers reported their work on the use of chiral phosphinoylalcohol complexes of MoVI for the epoxidation of a number of olefins [216]. The authors ruled out a mechanism of coordination of olefin to the metal center and opted for a situation in which two or more mechanisms were at work for which predominance of a single one being determined by the actual reaction conditions used. Carried out under catalytic conditions (olefin : catalyst ratio of 200). Table 7.219]. ca. In the former. In the case of complex MoO(O2)2·70 epoxidation of hept-1-ene was carried out under both stoichiometric and catalytic conditions. The ee’s determined were in the 2–39% range (see Table 7. Such mechanistic proposal had been previously suggested by Thiel [218. Ligand 64 65 66 67 68 69 70 70 a b Conversiona / % 72 55 77 39 47 80 35 >70b ee / % <2 0 <2 9 23 8 3 3 All reactions carried out under stoichiometric conditions (olefin : catalyst ratio of 10). for some selected results). Chart 16 71 72 Shortly after. Based on a model (Chart 15. using tbhp as terminal oxidant (Table 7. it was raised that the mechanism most likely involves a direct attack of the olefin on one of the peroxo oxygen atoms [217]. 3% in both cases.Recent Evolution of Oxidation Catalysis by Mo Complexes 69 The resulting complexes were screened in the epoxidation of both terminal and disubstituted olefins under both stoichiometric and catalytic conditions. 63) it was also suggested that both O1 and O3 should be the transferred oxygen atoms as they are proximal to the chiral ligand. and asserted that despite the environment near O1 being different to that around O2 it is the rate of oxygen transfer that dictates the degree of enantioselectivity. the catalytic reaction outperformed most probably based on a different mechanism. entries 7 and 8). under stoichiometric and catalytic conditions [216]. Epoxidation of hept-1-ene with MoO(O2)2L (L = P ligands in Chart 15) complexes and tbhp. Yoon and co-workers reported the preparation of MoVI-oxodiperoxo complexes based on (R)-piperidinylphenylacetamide 71 and (R)-piperidinylmandelamide 72 . Although ee’s were very low. d.70 Carla D. = not determined.and cis-β-methylstyrene were transformed to the corresponding epoxides [221]. Epoxidation of the latter was found to be unselective and additionally ees were not reported. Both have been tested in the catalytic epoxidation (2. ee / % 2 1 0 5 6 n. Vaz (Chart 16). the preparation of the first chiral MoVI-oxodiperoxo complexes 73.d. and despite moderate yields. . Under the conditions used. Later on in 2004. The highest ee (81%) was obtained using trans-β-methylstyrene and complex 72. Nunes and Pedro D. At the same time. which was used in a series of stoichiometric and catalytic olefin epoxidations with tbhp [222]. 74 containing N/O ligands (Chart 17) were reported [143]. a new report on the synthesis of 2(1-pyrazole)pyridineoxodiperoxo MoVI chiral complex 75 (Chart 17) has been presented. Chart 17 73 74 75 Table 8. Aromatic olefin epoxidation using 2-(1-pyrazole)pyridineoxodiperoxo MoVI chiral complex 75 and tbhp [222]. Olefin Conversion / % 31 86 28 37 44 49 n. and the first report of a catalytic epoxidation using this type of complex when both trans. they were able to achieve moderate to good ees (26–81%).5 mol% catalyst) of cyclooctene and (R)-limonene in the presence of tbhp. due to small yield of epoxide. (3) fast on/off exchange of ligands or part of ligands from the coordination sphere of MoVI peroxy complex. Chart 18 76 77 78 79 In face of these and previous results. (2) labile nature of the peroxy ligand. led to almost no ee (Table 8). As in previous reports. This as well as exchange between coordinated alkyl hydroperoxides and alkoxides has recently been demonstrated on the basis of some DFT calculations [89]. weak coordination has been recently proposed by Barlan and co-workers [225] to explain the lack of success using such epoxidizing system. Chart 18. In further attempts. being this the active catalytic species [89]. to form chiral alkyl hydroperoxide MoVI species in situ. Fast on/off exchange of ligands or part of ligands mentioned above from the coordination sphere of MoVI peroxy complex could have been the reason for lack of enantioselectivity in the last system discussed above [223]. led to the study of series of chiral pyridines and pyrazoles. it was proposed that the mechanism would involve a coordinated alkylperoxide to the MoVI species. which had been alluded to by Mitchell and Finney [224]). This arises from epoxide decomposition due to oxidative cleavage under the reaction conditions used.219] involving oxygen transfer from the coordinated alkylperoxide addition and (ii) direct transfer of an oxygen to the olefin from one of the peroxo oxygen atoms of complex 75 [217]. In fact. no enantioselectivity was observed in these reactions. Under the same conditions an excess of cyclohexene originated the corresponding epoxide along with cyclohexane-1.2-diol.Recent Evolution of Oxidation Catalysis by Mo Complexes 71 In the latter case the catalytic epoxidation reactions. This result led to the suggestion that catalytic olefin epoxidations could be based on two possible mechanisms at work: (i) that suggested by Thiel [218. This is most probably the key reason why only poor to fair enantioselectivities are obtained using oxoperoxo MoVI catalysts in olefin epoxidation. excess styrene was treated with the same complex being benzaldehyde the sole product. Continuation of this subject [223]. In a sequel of the work [221]. particularly at high temperature during reaction. lack of enantioselectivity was put down to the following reasons: (1) presence of other chiral or achiral MoVI peroxy or peroxo species in solution competing with the principal oxoperoxy complex (multiple catalytically active species. leading to generation of a number of competing diastereomeric transition states. . Catalytic oxidation of olefins. Substrate Product Temp.72 Carla D. alcohols.231]. / K 298 Yield 91 96 98 90 70 90 87 97 313 91 97 353 81 98 63 89 60 88 96 96 96 78 . Nunes and Pedro D. Vaz Table 9. amines and sulfides using [MoO(O2)2(hpeoh)]− [hpeoh = o-C6H4(OH)−C(CH3)=N−OH] (80). H2O2 and NaHCO3 in acetonitrile [230. Recent Evolution of Oxidation Catalysis by Mo Complexes 73 Over the last decade the Thiel group have conducted exhaustive studies on this catalytic reaction using 2-(pyrazol-3-yl)pyridinyloxodiperoxo MoVI complexes in both homogenous [218. is that the two electrophilic oxygen atoms are disposable to the incoming nucleophilic olefin. Another important reason in the case of the oxodiperoxo MoVI complexes. evidenced that ligand dissociation appeared to occur. To circumvent this problem and develop catalysts that can reach high eneantioselective products one must realize that: (1) stronger non-dissociating chiral ligands are to be used. oxygen to olefin transfer rates are different. (2) the rate difference of the oxygen transfer from the two peroxo ligands must be accentuated. An additional novelty was the use of a room temperature ionic liquid (RTIL) as reaction medium. More recently some more works have been published concerning oxidation of a variety of substrates using MoO(O2)2 complexes with pyridine and phenol oxime derivatives as ligands [230. and due to the symmetric disposition of the two peroxo groups both enantiomers of the oxirane product should be obtained. This point had previously been mentioned by Ross [216]. reported the epoxidation of cyclooctene in the presence of MoO(O2)2(4-MepyO)2 and using urea hydrogen peroxide complex (uhp) as oxygen source. entry 14). use of NaHCO3 seems to lead to different regioselectivity as evidenced by the oxidation of cinammyl alcohol which in its presence yields the epoxide as the sole product with 70% (Table 9. . Noticeably. depending on the system. Most probably.231] and using H2O2 as oxidant and in the presence or absence of NaHCO3 as a co-catalyst. In both cases selectivity is 100% to the respective oxidation product. Such findings by Thiel and co-workers identified the principle reason why the asymmetric induction is so weak in such systems. particularly [C4mim][PF6] (1-butyl-3-methyl-1H-imidazol-3-ium hexafluorophosphate). At the same time the Gallindo group [232]. but not enough to provide high enantioselectivities. showing that conversions are quite high across substrates. In addition and according to the authors. at a different temperature though. In addition. When in the absence of NaHCO3 the same substrate under similar reaction conditions leads to cinnamylaldehyde in 89% yield (Table 9. these works although recent. giving the corresponding epoxide with 83% yield. One combined study by this group [229] using both NMR experiments and DFT calculations. Results are summarized in Table 9. entry 5).219] and in heterogeneous phases later on [226–228]. stress the demand for more robust catalysts based on the point raised above in this chapter. ligand dissociation from metal is the reason why rates of oxygen transfer are not significantly different. Substrate conversion was found to reach a maximum of 89%. (3) additional efforts must be spent developing and testing chiral monoperoxo complexes holding strongly coordinating chiral ligands. Despite no ee’s have been reported it should be mentioned that in most cases selectivity is quite high. Still. Activation energies required (89–110 kJ·mol–1 in Thiel’s study) for ligand dissociation are provided by high temperatures required for successful epoxidation reactions. a series of complexes containing the Cp ligand with ansa bridges were also prepared and its catalytic performance reported. oxidant and olefin) but also to its achievements. The set of catalytic systems tested since then is resumed in Table 10. an increasing awareness on the use of precatalysts has been observed [33. Such pre-catalysts are simply organometallic MoII carbonyl complexes which can be oxidized to the dioxo MoVI homologues. Such approach has proved quite adequate as kinetics as well as conversion and yields are superior (Table 10. After those results have been reported. The original idea behind the synthesis of ansa-bridged compounds was to hinder Cp-loss after possible intermediate ring slippage. 5) for both the case of cyclooctene and limonene. due to considerable ring strains under oxidative conditions [239]. an oxo-peroxo Mo acetylide moiety and formation of organic phase of the product (aldehyde) have enabled very easy and efficient recycle of this homogeneous catalyst even up to five recycles without appreciable loss in conversion and aldehyde selectivity. The very first example of a complex of this family was CpMoO2Cl reported in 1963 by Cousins and Green [234]. excellent selectivities have also been reached. followed. with maximum selectivity. Comparison of the catalytic performance with the use of the dioxo complex was found to produce similar results. The results show that the Mo acetylide complex is very efficient catalyst for accomplishing such transformation [238]. The dioxo complex mentioned above was synthesized in very low yields and surprisingly as the only isolable product from air oxidation of CpMo(CO)2(π-C3H5) in the presence of HCl.233]. and derived from the above mentioned Cp complexes. Introducing chirality with a chiral substituent on the Cp-ring has also been attempted. the water soluble nature of the catalytically active species. entries 2.38. as compared with conventional oil bath heating. other works concerning the direct use of MoII carbonyl complexes as precatalysts. which are then oxidized in situ to yield the active species. More recently. Such system can very well tolerate electron-rich as well as electron-withdrawing substituents on aromatic ring. accounting not only for the catalytic system used (precatalyst complex. From data shown in Table 10 concerning cyclooctene epoxidation it should be mentioned that the work of Abrantes et al. It was also found that under the catalytic reaction conditions the tricarbonyl complex rapidly yields CpMoO2Cl which was reported to be the active species. According to the authors. Ansa-bridged derivatives have been used to introduce chirality in the system by transforming the bridging C atoms into chiral centers. [236] has used microwave radiation as a convenient method to perform the heating of the catalytic tests. Vaz OXIDATIONS WITH [MOII(CO)2. it turned out that ansa-bridges with only two carbon atoms in the bridge are not sufficiently stable. In the case of primary alcohol oxidation yielding the corresponding aldehydes. both complexes reaching identical performance in cyclooctene epoxidation (complete substrate conversion with 100% selectivity to the epoxide after 6h). 3 and 4. Nunes and Pedro D. From the recent evolution on the use of the latter carbonyl complexes it was found that these undergo oxidative decarbonylation to yield the corresponding organometallic MoVI dioxo congeners [235]. However.74 Carla D. obtained by oxidation of [CpMo(CO)3]2 and CpMo(CO)2(π-C3H5). In that work the group of Gonçalves showed possible the direct use of the CpMo(CO)3Cl carbonyl complex as a precatalyst for olefin oxidation using tbhp. .3]2+ COMPLEXES AS PRE-CATALYSTS Since the starting of the XXIst century. X Cp . CH3 82 tbhp 94 (mw) 86 100 100 100 100 84 236 tbhp 91 (mw) 80 Cp–COProBz .Recent Evolution of Oxidation Catalysis by Mo Complexes Table 10. CH3. Cp’ = Cp or Cp derivatives) complexes. last 3 entries) as the regular ansa-Cp . Complex Cp’ . Aryl . 235 75 Cp . Catalytic performance in olefin or primary alcohol oxidation using Cp’Mo(CO)3X (X = Cl. Cl 81 Oxidant tbhp Substrate Conversion 100 Selectivity 100 Ref. CH3 83 tbhp 100 237 Cp-CCPh . C≡C–Ph 84 H2O2 86 92 238 87 87 90 90 60 88 65 91 72 82 70 75 82 88 82 85 In the case of the use of N-heterocyclic carbene Cp derivative ligands. reported by Royo’s group [240] these were not as active (Table 11. Nunes and Pedro D. 100 85 100 86 239 100 87 100 88 100 89 25 90 25 91 240 11 92 . holding the most bulkier Cp derivative showed a high activity towards cyclooctene epoxidation (Tabel 11. I) in cyclooctene epoxidation. Vaz derivatives reported by Kühn. Complex Yield Ref. Catalytic activity of ansa-CpMo(CO)2X (X = CO. Table 11. last entry). In fact only one of the catalysts.76 Carla D. Recent Evolution of Oxidation Catalysis by Mo Complexes 77 91 93 Table 12. X Cl L CH3CN 94 Conversion / % 100 Ref. Catalytic activity of Mo(η3-C3H5)X(CO)2L complexes in olefin epoxidation. 241 N N 95 95 241 88 96 241 100 97 99 98 100 99 Br CH3CN 100 100 241 242 243 241 100 101 99 102 64 103 45 104 241 242 244 244 . . entry 6) was found to be more active in cyclooctene epoxidation than the Cp counterparts (Table 11. as evidenced in Table 12. Br. Ln = mono or bidentate lewis base ligands) complexes have also been reported in recent years [241-246].78 Carla D. Table 13. Epoxide yields were found to reach almost 100 % in many cases stressing the usefulness of such association. Vaz 80 105 33 106 64 107 245 245 246 In a different though parallel perspective. These works screened over quite some ligands. In fact such system (Tabel 12. related catalytic systems using Mo(η3C3H5)X(CO)2Ln (X = Cl.N’ bidentate ligands but in some cases it was found that when the ligands hold N–H moieties deactivation does occur with conversions dropping down drastically (Table 12). 247 247 13 112 248 9 113 248 In fact it was found that catalytic activities were very dependent on the type of ligand used. Nunes and Pedro D. More recently the use of carbene ligands in these allyl complexes has been reported showing good activities using H2O2 as oxygen source [243]. Catalytic activity of MoX2(CO)3L complexes in cyclooctene epoxidation. 3 last entries). X Br L CH3CN 108 Conversion / % 100 88 109 I CH3CN 110 81 63 111 247 247 Ref. Generally the ligands used relied on N. CH3) complexes has by far been the mostly studied across years as compared to the other mentioned carbonyl systems based on the Mo(η3-C3H5)X(CO)2Ln or the MoX2(CO)3Ln (X = Cl. In fact a survey on such ligands has permitted to establish an important ligand structurecatalytic activity relationship stressing the importance of the inexistence of deactivating N–H moieties. Ln = mono or bidentate Lewis base ligands) halocarbonyl families reported above in this chapter. Br. These complexes were developed in pioneering work by Baker for catalytic applications other than oxidation [249]. The synthesis of Cp*MoO2Cl [Cp* = η5-C5(CH3)5] was obtained by oxidation of the dimeric carbonyl complex [Cp*Mo(CO)2]2 with O2 in chloroform and subsequent treatment of this intermediary with PCl5. To this concern the chemistry of CpMoO2X and CpMo(CO)3X (X = Cl. leading also to other species such as mono oxo and dimeric complexes.or bromoform) and with O2. This is shown in Figure 1. I. Br) complexes. such systems were found to have quite high performances. As in the first method. Scheme 5. Br. although it was found very recently that such systems suffer from the same ligand dependency which leads in some cases to deactivation. Table 13. This complex exhibited good thermal stability being also able to be manipulated in dry air. Ln = mono or bidentate Lewis base ligands) heptacoordinate halocarbonyl family were also reported to possess catalytic activity in olefin epoxidation [247. yields were also reported to be very low. Br) complexes (Chart 19) [250-252]. Cousins and Green were the first authors to rationalize several synthetic methods for obtaining the CpMoO2X (X = Cl.Recent Evolution of Oxidation Catalysis by Mo Complexes 79 The use of related though different complexes from the MoX2(CO)3Ln (X = Br. along with both ease of preparation and separation from other reaction products. 114 Both derivatives showed to be stable under inert N2 atmosphere. One of the methods consists in the irradiation of [CpMo(CO)3]2 in a solution of the haloform of interest (either chloro. decomposing slowly under air and rapidly in solution.254]. Attempts at understanding the mechanistic aspects of the transformation of the MoII carbonyl precursors into their MoVI dioxo congeners by means of an oxidative decarbonylation process have been the aim of quite some works. However. yielding a μ-oxo bridged dimer. These difficulties have surely been the cause for a gap between these early works and the next publications dealing with Cp dioxo molybdenum complexes which have emerged in the late 1980’s [253. Such synthetic procedure was a . This is the result of relatively unspecific synthetic pathways. This is true when ligands hold NH moieties as already discussed a few lines above in this chapter [248]. Chart 19 81. which affords the desired CpMoO2X (X = Cl.248]. I. The first records dealt mainly with the development of proper methods of preparing the CpMoO2Cl complex from CpMo(CO)3Cl. yields Cp*MoO2Cl [255]. In a parallel pathway the chloride carbonyl Cp*MoCl4 precursor complex discarded the need to conduct the reaction in chlorinated solvents. Vaz substantial improvement in comparison to its Cp counterpart previously described by Green [234].80 Carla D. The several synthetic pathways developed for Cp*MoO2Cl (58) are also summarized in Scheme 5. The numbers adjacent to ligand names refer to the respective reference. Ligand structure–catalytic activity relationship from MoII based complexes for cyclooctene conversion. . Nunes and Pedro D. Figure 1. Cp*) and will be briefly addressed in the following lines. In particular irradiation of Cp*Mo(CO)3Cl in toluene under an O2 purge and UV radiation for 2 h . This scheme stresses the different synthetic routes as well as its efficiencies in both terms of reaction time and product yield. Several other methods have emerged in the following years for the synthesis of Cp’MoO2Cl (Cp’ = Cp. Reaction times lower than 30 min. Such dimeric complex is likely formed via hydrolysis of Cp*MoO2Cl generating Cp*MoO2OH. 2 h (Scheme 5). Despite this. In fact. Dimethyldioxirane was found to be unable to oxidatively decarbonylate to (η5C5R5)MoO2Cl in contrast to other systems [260]. including treatment of [Cp*Mo(CO)2]2 with 30% hydrogen peroxide and HCl [258]. in the absence of air (N2) led to the formation of Cp*MoOCl2. the base used in these reactions is not innocent on the products obtained. when Cp*MoCl4 reacts with t-BuNH2 in the presence of water and air the [Cp*MoO3]– anionic trioxo complex is formed being isolated as its [t-BuNH3]+ salt. When reaction times longer than 30 min are used the formation of the μ-bridged oxo dimer [Cp*MoO2]2O is obtained. A few other methods have since then been reported [257. evidences the latter method of oxidative decarbonylation of (η5C5R5)Mo(CO)3Cl provides a more general route comprising different derivatives of the Cp . Synthetic pathways for preparation of Cp*MoO2Cl (see text for details). On the other hand in the presence of air Cp*MoO2Cl is obtained. Subsequent treatment of this complex with gaseous HCl gives Cp*MoO2Cl neatly. which then undergoes condensation by loss of H2O. The desired complexes could be obtained in yields reaching 75% by stirring a CH2Cl2 solution of the carbonyl precursors with excess of tbhp for ca.258].Recent Evolution of Oxidation Catalysis by Mo Complexes 81 Scheme 5. In this context the former complex seems as the logical intermediate to the dioxo complex. CH3. This complex was found to yield Cp*MoO2Cl by reaction with aqueous NaOH in the presence or absence of air [256]. Comparison with previously described synthetic routes. A major improvement on the synthesis of (η5-C5R5)MoO2Cl (R = H. CH2Ph (Bn)) complexes from their corresponding and readily available (η5-C5R5)Mo(CO)3Cl precursors was reported in 2003 [259]. including stopped-flow kinetic analysis.4. In this way. with tbhp as oxidant. geraniol.2.5-tetramethylcyclohexa-1. However.4-diene). Br. Apart from tbhp.82 Carla D.t. (η5-C5Bn5)MoO2Cl is significantly more stable than its Cp and Cp* congeners. showing no observable oxidation of the Cp* ligand as evidenced by 1H NMR data [255]. rendering the Cp*–MoVI species unable to form extended oligonuclear aggregates. Vaz ring. the authors found that tbhp would react with Cp*MoO2Cl yielding also the Cp*Mo(O2)OCl complex.5dimethoxyphenyl) [261]. as long as they do not include any electron-withdrawing groups. Reactions were conducted at 328 K using catalyst loadings of 1 mol%. Similarly. the catalyst precursor Cp*MoO2Cl seems to maintain its integrity during the catalytic reaction. thus confirming previous findings [265]. The study of the catalytic properties of the (η5-C5R5)MoO2Cl [R = H. on-line electrochemical flow-cell and electrospray mass spectroscopy [262–264]. As a consequence this blocks three coordination positions. CH3] many other studies dealt with the catalytic applications of these and other complexes not only in olefin epoxidation (the majority of examples) but also in the oxidation of other substrates. who analyzed the X-ray crystal structure of Cp*Mo(O2)OCl and also described this compound as being not active as olefin epoxidation catalyst in the presence of excess tbhp. This complex was shown to act as active catalyst for the epoxidation of several olefins (such as cyclooctene. relative rates depend on structure of the alkyl group of peroxide and catalyst loads of 2–5% were used depending on substrate and reaction temperatures spanned from r. CH3. resists hydrolysis down to pH zero. CH2Ph (Bn)] complexes as catalysts for the epoxidation of cyclooctene. When in the absence of olefins. reported speciation studies of Mo complexes containing the Cp* ligand over the entire pH range in an essentially pure aqueous environment by several methods. but are rather moisture sensitive in solution. Although many efforts have been devoted to the preparation of the above mentioned (η5C5R5)MoO2X [R = H. and being concluded that the active species cannot be a η2-coordinated peroxo complex. Such studies revealed the existence and stability of Cp*MoO2OH and [Cp*MoO2]+ complexes as a function of pH. X = Cl. The catalytic activity of dioxomolybdenum complexes containing cyclopentadienyl ligands was – until recently – solely examined for Cp*MoO2Cl by Bergman and Trost [255]. probably due to steric bulk effect of the Cp ligand. Catalytic reactions performed with the isolated Cp*Mo(O2)OCl did not lead to any oxidation products. Consequently this species was considered to be an unwanted side product. CH2Ph (Bn). The authors also concluded that the inertness of the Cp*–Mo bond. a striking increase in stability. These results were later supported by Roesky et al. when H2O2 and thp were used no catalytic reaction occurred and the oxo-peroxo complex Cp*Mo(O2)OCl was formed. All three compounds originally described in that work can be handled in air for brief periods of time. other alkyl hydroperoxides such as cumyl hydroperoxide and n-hexylhydroperoxide could be used as oxidants. Apart from formation of Cp*Mo(O2)OCl. Nunes and Pedro D. (room temperature) to 333 K. even in comparison to Cp*MoO2Cl had also been previously observed with the compound (η5-C5Ph4R)MoO2Br (R = 2. styrene and 1-octene has been extended [259]. 1. At the same time Poli et al. CH3 (Me). Influence of ring substituents on catalyst activity was studied in detail . The effect of the alkyl peroxide used on the relative rate of the epoxidation reaction was investigated and the obtained rates were consistent with formation of an intermediate species in which the alkyl group of the peroxide moiety is intact. 01%. unfunctionalized olefin reacts significantly slower than the other substrates. the initial [(η5-C5Ph4R)MoO2Br] (R = 2. Ring opening of the styrene epoxide to the diol is not significant under the conditions applied. due to a weaker Mo-ring bond. most probably. at these low catalyst loadings the residual amount of water present in the system gains increasing influence on the catalytic performance after some time and consequently. while that of the Cp derivative declines strongly due to catalyst decomposition. Recharging the catalytic system with . CH3. However.5-dimethoxyphenyl) complex leads to a species A which is catalytically active. That study was motivated by the fact that the same authors had in a previous report demonstrated that (η5-C5Ar5)MoO2X complexes may exhibit exceptional stability. Based on 1H NMR data. according to Scheme 6. though it transforms into a transient species B. given the marked dependence of catalytic efficiency on the cyclopentadienyl substituent. catalytic runs were performed using a catalyst load of (η5-C5Bn5)MoO2Cl as low as 0. Similarly (η5-C5Me5)MoO2Cl reaches only about 60% of the activity of the other derivatives in the first run and shares the same decomposition problems observed for (η5-C5H5)MoO2Cl under catalytic conditions. Using this latter mentioned complex it was found that the epoxidation mechanism must involve. despite its higher steric bulk. in a second and third catalytic run (by addition of new substrate) the complex (η5-C5Bn5)MoO2Cl maintains most of its activity. species C will be the only Mo-containing species present. reaching 100% conversion after 4 h reaction time. was ascribed both to its higher stability towards moisture and the lower electronic density at the Mo center. species C is the active catalyst that dominates the faster phase. three species. CH2Ph (Bn)]. Scheme 6. By the end of the catalysis run. This means that in the process CO ligands are not involved in any oxidation process. the best results being again obtained with complex containing the bulkier ligand. and lowering the Mo compound load to 0.Recent Evolution of Oxidation Catalysis by Mo Complexes 83 for cyclooctene. According to the authors and. TOFs (turnover frequencies) of 4000 h-1 were achieved. that in a recent work an in-depth study based on kinetic data has been accomplished by the Colbran group [266]. 1octene.1% under the same reaction conditions. However. According to the kinetic model. Such statements were published based on several spectroscopic observations in which the authors proved that the oxidative decarbonylation process proceeds via the release of CO rather than CO2. Epoxidation of styrene and 1-octene was also successful using (η5-C5R5)MoO2Cl [R = H. When Gonçalves first reported on the use of CpMo(CO)3Cl as a precatalyst that could be used directly for catalysis which would undergo oxidative decarbonylation in situ it was mentioned that CpMoO2Cl was the active catalyst [235]. According to the model. as reflected in 95Mo NMR and vibrational spectroscopy. however. in comparison to the derivatives (η5-C5Me5)MoO2Cl and (η5-C5H5)MoO2Cl. It should also be mentioned. no (η5-C5Ar5)MoO2Cl (Ar = aryl group) complex had been screened for epoxidation catalysis. such as the [(η5-C5Ph4R)MoO2Br] (R = 2. values of 20000 h-1 were reached. species C is formed by loss of the cyclopentadienyl moiety. being an unactivated. Due to its high stability and activity. the catalytic activities decrease considerably after 1 h reaction time for the lowest catalyst amounts applied [259]. the high activity of this complex. According to the authors. Both (η5-C5H5)MoO2Cl and (η5-C5Bn5)MoO2Cl complexes show good activity. though it converts into species C which will be the active species. This latter species is predicted to be inactive.5-dimethoxyphenyl) complex already mentioned previously in this chapter [261]. In this way presumption of complete stability for an alkylcyclopentadienyl MoVI oxo catalyst during epoxidation catalysis may be unfounded. First. . the Cp ligand is lost from Mo as the catalysis proceeds. Scheme 6. The latter finding evidenced that loss of the Cp’ ligand from a Cp’MoO2X catalyst. either Mo(η3-C3H5)X(CO)2Ln or MoX2(CO)3Ln (X = Cl. Scheme 7.269] with trends in parameters such as the steric bulk of the ring substituents as well as either the tendency or ability of the Cp to undergo catalysis-facilitating ring slippage was found to have its cause in loss of the alkylcyclopentadienyl ligand. Poli’s group has revealed a varied and rich aqueous chemistry in its speciation work under varying pH conditions as already mentioned in this chapter [264].3) × 10–5 s–1 . even if only slight.3 (±0. should always be considered in alkene epoxidation catalyzes. It was found for the former that the mechanism proceeds through a combined cycle involving two possible pathways. Second. Br. Difficulties that have been previously encountered in reconciling kinetic data [33. Those works have finally shed some light on what was happens behind the scenes concerning such catalysts with Cp ligands. (perarylcyclopentadienyl) MoVI dioxo species do catalyze alkene epoxidation. Vaz cyclooctene and tbhp at this point leads to immediate catalysis consistent with species C remaining present and active at the end of the run. Nunes and Pedro D. Mechanistic model proposed according to kinetic data (k1 ≈ k2 > 5 × 10–5 s–1 . Of course it is now hoped that work is to be carried out to reveal how other related systems behave. kB ≈ 0 s–1) [266].95.101.268.271]. even in trace amount.94. Two insights followed from this information. I. 35·kA ≈ kC = 7. Most recently the mechanism of olefin epoxidation using CpMo(CO)3(CH3) has been clarified based on both kinetic data and DFT calculations [270.259. Ln = mono or bidentate Lewis base ligands) halocarbonyl families which are also active players in such chemistry. Although. indeed they have also showed that loss of the Cp* ligand may occur under certain conditions [267].84 Carla D. leading to the in situ generation of a much more efficient catalyst. because the thus-formed Mo species C may be the most active catalyst. to afford a more active MoVI (per)oxo species. According to the authors this complex has quite some differences as compared to its homologue CpMo(CO)3Cl. but also to understand what happens behind the scenes during the catalytic cycle. CONCLUSION The present chapter aimed at an overview of recent literature concerning the role of Mo complexes in oxidation chemistry. the fact is that imagination seems to be the limit as given by the increasing number of works dealing with several aspects. MoVI-oxo core. promoted by the mentioned industrial processes that raised the interest of the scientific community. Behind such interest one can find the usefulness of the industrial processes developed by ARCO and Halcon in the late 1960’s [81. testing new oxidants and reaction conditions or by performing oxidation reactions in substrates other than olefins. Despite this. although catalytic applications have only been exploited with more interest starting in the 80’s decade of the XXth century. Regardless of this. Overall mechanism for the oxidation of CpMo(CO)3(CH3) by tbhp and the epoxidation activities of the resulting oxidated complexes CpMoO2(CH3) and CpMoO(O2)(CH3) [270. This latter aspect was clearly illustrated by some fine examples of sulfide oxidation. The first complexes were developed about 50 years ago. This ranges from preparing different (and more efficient) catalysts. and in fact they do. whose reactions in some cases were shown to be tuned so that . namely [MoVIO2]2+. Proof of this are many works which have reported on kinetics and DFT studies of the respective mechanisms. [MoVIO(O2)]2+ and [MoII(CO)2.82]. After reading this chapter one may think that in a way all topics merge to a common end. as discussed in this chapter. This is evidenced since the dioxo core may lead to oxo-peroxo and that the carbonyl precursors originate the dioxo and subsequently the oxo-peroxo (Scheme 7).Recent Evolution of Oxidation Catalysis by Mo Complexes 85 Scheme 7. mainly in olefin epoxidation. the view presented here shows the panorama of the present state of the art concerning Mo oxidation chemistry as given by three main topics discussed above. 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Organometallics 2009.Recent Evolution of Oxidation Catalysis by Mo Complexes 95 [260] Wolowiec. . Co(II).K.ru> .A. V(III). L. Boreskov Institute of Catalysis. For the first time the number of active centers and propagation rate constant for ethylene polymerization with Fe(II).V. i-Pr. t-Bu. The effects of the activator nature (different samples of methylalumoxane (MAO). M= Fe(II). Matsko and V.V. Co(II). Poehler ISBN: 978-1-61122-894-6 © 2011 Nova Science Publishers. Russian Federation ABSTRACT The family of highly active ethylene polymerization catalysts based on the complexes of transition metals with bis(imino)pyridine ligands has been intensively studied in the last ten years. Inc. Siberian Branch of the Russian Academy of Sciences 630090. E –mail address: N.:+7(383)326 95 51. Novosibirsk. Cr(III). Tel. Me. have been determined using method of polymerization inhibition by radioactive carbon monoxide (14CO).6-(2. Co(II). activated with MAO and Al(i-Bu)3. molecular weight distribution. V(III) and Cr(III) bis(imino)pyridine complexes with close ligand framework (2. A. Echevskaya. COBALT. content of methyl and vinyl groups) have been studied. n=2.In: Homogeneous Catalysts Editor: Andrew C.Semikolenova <nvsemiko@catalysis. number of * Corresponding author. or aluminium trialkyls) and polymerization conditions on the activity of these complexes and the resulted PE structure (molecular weight. VANADIUM AND CHROMIUM: THE KINETIC PECULIARITIES OF ETHYLENE POLYMERIZATION N. L=(C6H3N=CMe)2C5H3N. The experimental data obtained in comparable conditions have shown that the catalytic properties of bis(imino)pyridine complexes ( polymerization activity.4.A. Chapter 3 HOMOGENEOUS CATALYSTS BASED ON BIS(IMINO)PYRIDINE COMPLEXES OF IRON.A. Semikolenova*. Cr(III) and V(III) bis(imino)pyridine complexes.3). where R= H. M. Zakharov G. In this study we summarize the known data and present new kinetic results on the ethylene polymerization over homogeneous catalysts based on Fe(II).6-R3LMeCln.G. Barabanov. 8] and Gibson [9. who have shown that nickel and palladium complexes with bulky a-dimine ligands are capable of polymerizing ethylene to high molecular weight polymers [2]. A. Et. polyethylene.6-bis bis(imino)pyridine complexes of iron (II). considerable efforts have been devoted to the discovery of new families of catalysts based on the complexes of non-metallocene nature. INTRODUCTION The olefin polymerization catalysts based on soluble well defined transition metal complexes.6-bis(imino)pyridine complexes (M=Fe(II) or Co(II). providing access to polymers with new or improved characteristics. Barabanov. RnLMCl2. t-Bu. Semikolenova.G.the substituents in the arene ring of the ligand L ) when activated with methylaluminoxane (MAO) form extremely active homogeneous catalysts for ethylene polymerization to linear polyethylene (PE). This discovery has stimulated rapid development of new generation of “post-metallocene” catalysts. R1. composition of optimal activator.6-bis(imino)pyridine complexes of iron and cobalt (Scheme 1.V. i-Pr) .6-positions of arene ring in the ligand L affects the number of active centers and molecular weight of PE as well.R3 = H. In the last ten years the catalysts based on bis(imino)pyridine complexes have attracted much academic and industrial interest and were intensively studied. R= Me. During the 80s large efforts were devoted to creation of the group 4 metallocene systems. where M=Fe(II) or Co(II). This type of catalysts is easer to synthesize and they are more tolerant to polar groups than metallocenes. An important advance in this direction was made by Brookhart and co-workers. chromium (III) and vanadium (III). It was reported by Brookhart [7.A. Rn . formation of single site or multiple sites catalytic system. The size of the substituents R in 2.R2. Advances in this field are broadly covered in a number of reviews [3-6]. complexes of transition metals with polydentate nitrogen-containing ligands are considered as one of the most promising families of post-metallocene catalysts. To expand the range of the produced polymers. ethylene polymerization. L. catalysts thermal stability and PE structure) are mainly determined by transition metal center of complex. is currently a subject of great academic and industrial interest. cobalt (II). At present. copolymerization reactivity. Me.98 N.10] that 2. The advances in the development of metallocene and their related half-sandwich (“constrained geometry”) catalysts [1] gained the insight into the nature of the activated species and the possibilities for controlling the polymeric products structure and resulted in a number of commercial processes for preparation of new polyolefinic materials. active centers and propagation rate constant.6-bis(imino)pyridine ligand. Scheme 1 The structure of iron and cobalt 2. Echevskaja et al. molecular weight distribution 1. L= 2. Keywords: 2. The size of the substituents R in 2. . V(III) and Cr(III) bis(imino)pyridine complexes.).6 positions of the arene ring in the ligand L affects the number of active centers and molecular weight of PE as well. In this study we summarize the known data. catalysts thermal stability and PE structure) are mainly determined by transition metal center of complex. giving the possibility to obtain polymers with different value of Mw – from oligomers to high molecular weight PE. Such an approach hinders the ascertainment of patterns in the catalytic properties of these systems since the catalytic activity and the molecular structure of the resulting PE are affected by the polymerization conditions (catalyst concentration. polymerization temperature etc. Highly linear PE samples are obtained with iron and cobalt bis(imino)pyridine complexes. it have been shown that vanadium(III) [16-18] and chromium(III) [19-21] complexes with bis(arylimino)pyridine ligands can be regarded as promising catalysts for ethylene polymerization. CATALYSTS BASED ON RNLFECL2 Effect of Activator The data on the activity of homogeneous catalytic systems composed of 2.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 99 During further investigations it was found [11-15] that iron bis(imino)pyridine complexes can be activated with common aluminium trialkyls (AlMe3.7-10]. Co(II). activated with MAO and Al(i-Bu)3 the number of active centers and propagation rate constant have been determined using the method of polymerization inhibition by radioactive carbon monoxide (14CO). 2. The experimental data have been obtained under comparable conditions allowing us to reveal the effect of the transition metal on the catalytic properties of the homogeneous catalysts based on bis(imino)pyridine complexes. Al(n-Oct)3). in the literature the data on the catalytic properties of the systems based on bis(imino)pyridine complexes of various composition are discussed separately. copolymerization reactivity.1. including those obtained by ourselves [12. formation of single-site or multiple-sites catalytic system. A detailed study on the effect of the activator nature and the ligand composition on the catalytic behavior of bis(imino)pyridine complexes and the resulting PE structure has been undertaken. Al(i-Bu)3. number of active centers and propagation rate constant. Co(II). The experimental data obtained under comparable conditions have shown that the catalytic properties of bis(imino)pyridine complexes ( polymerization activity. 22-35] and present new results on the polymerization properties of homogeneous catalysts based on Fe(II). Later. that substantially simplifies the catalytic systems and broadens the possibilities of their use in the polymerization processes. the nature and amount of the activator. Commonly. composition of optimal activator. Cr(III) and V(III) bis(imino)pyridine complexes.6-Me2LFeCl2 with different activators and structure of the resulted PE are summarized in Table 1. For ethylene polymerization over Fe(II). AlEt3. The values of molecular weight (Mw) and molecular weight distribution of the resulted PEs are governed by the substituents in phenyl rings of the ligand [5. all other conditions as run 11) 2) 3) 4) Calculated according to Figure 1 IRS data The kinetic curves for correspondent polymerization runs are shown on Figure 1. Al/Fe=500.5 1.2 0. (5) Al(i-Bu)3 (6) Al(n-Oct)3. L.4 × 10-5 mol/l. min 20 5 2 4 6 30 Figure 1.0 6.4 - 1) Polymerization in toluene at 35 ºC. (4) AlMe3 . Barabanov. Ethylene polymerization over 2.0 0. Echevskaja et al.9 1. [Fe] =1.9 - 1) 1) 2) 1) 2) 1) 1) 1 2 3 4 5 6 7 MAO MAO (50) MMAO AlMe3 Al(i-Bu)3 Al(n-Oct)3 Ph3C[B(C6F5)4] + Al(i-Bu)3 71 75 106 115 46 - 8.3 4.5 1.6 12.4 1.9 1. ethylene pressure 2 bar.6-Me2LFeCl2 and different activators Run Activator Yield Kg PE/ mol Fe bar 9100 11000 6800 12300 7600 12300 470 Maximum activity.G. kg PE/mol Fe bar min 1 500 400 300 200 100 0 10 Time. .8 1. 600 Activity. (2) МАО(50).A.2 - 4) Content per PE molecule СН3 1.0 11.6 1.0 1.100 N. Table 1.8 1. × 103 Mw/ Mn Content per 1000 С СН3 СН= СН2 0.3 - 1 0. for 30 min.2 1.7 0.6 0. Kinetic curves for ethylene polymerization over the catalysts composed of 2.V.5 0.1 СН= СН2 0. Semikolenova. Polymerization in heptane.(Number on the curve corresponds to the number of the experiment in Table 1). Kg PE/ mol Fe bar min 500 330 430 300 250 320 20 3) Mw. A.6-Me2LFeCl2 and different activators: (1) MAO. but the latter rapidly fell with the polymerization time (Figure 1. The examined catalysts exhibited high initial activity decreasing in the course of polymerization (Figure 1). curve 2). The catalysts formed by interaction of iron complex with Al(i-Bu)3 and MMAO. Al(n-Oct)3).3. (2) МАО(50). (5) Al(i-Bu)3 (6) Al(n-Oct)3. run 7). runs 1 and 3) due to the higher stability of these systems (Figure 1. provided higher PE yield (Table 1. The catalyst obtained upon activation of iron complex with commercial MAO exhibited very high initial activity.6-Me2LFeCl2 and different activators: (1) MAO.2 0. 1. 6). show high initial activity in the polymerization in heptane medium (Table 1.6 0. The systems formed by 2. run 1. AlMe3 and Al(n-Oct)3 (Figure 1). The obtained polyethylene samples were highly linear (about one -CH3 and vinyl terminal groups per one PE molecule) (Table 1).) ( Wf= weight fraction. MWD of PE produced with homogeneous catalysts composed of 2. Table 1. The values of molecular weight and polydispersity (Mw/Mn values) depend on the activator nature.5 M and MAO sample with the reduced content of AlMe3 ( ~ 0. In contrast to metallocene catalysts. runs 3 and 5).4 0. Al(i-Bu)3 and Al(n-Oct)3 ) (Table 1).6-Me2LFeCl2 with two different MAO samples (commercial MAO with AlMe3 content ~0. a borate activator was not effective for iron bis(imino)pyridine catalysits (Table 1. M=molecular weight. causing the reduced yield of PE. Data in Table 1 and Figure 2 show that in the presence of MAO (50).) . run 2 . soluble in aliphatics. The system stability and PE yield depend on the activator nature.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 101 All examined systems exhibited low thermal stability and virtually lost polymerization activity at temperatures above 50 ºC. MAO modified with Al(i-Bu)3 (commercial sample.6.0 2 3 4 Log M 5 6 7 5 6 2 Figure 2. MAO(50)).001 M of AlMe3.(Number on the curve corresponds to the number of the experiment in Table 1. MMAO) and aluminium trialkyls (AlMe3. curve 1). Table 1. curve 1). Figure 2. curves 4. whereas the Mw/Mn value of PE sample prepared using commercial MAO was noticeably higher (Mw/Mn=8. These systems were less stable than that prepared using MAO purified from AlMe3 (MAO(50)). PE with the lowest polydispersity was obtained (Mw/Mn=4. 6) than that obtained in presence of MAO and MMAO (Table 1.6-Me2LFeCl2 interaction with aluminium trialkyls (AlMe3. Figure 2.8 d Wf/d log M 1 0.0 0. At 35 ºC highly active catalytic systems providing high PE yield were formed upon activation of 2. runs 4. in presence of MAO as activator. Fig 3). Broad molecular weight distribution (MWD) of the polymers formed in the presence of the catalysts composed of 2.G. L. × 10-3 71 220 15 Mw/Mn 8.A. ethylene pressure 2 bar. ketimine catalysts ( R= CH3-. Scheme 1): with the increase of steric bulk of the substiuents the Mw values of the produced PE increase. Effect of the substituents R on the activity of Rn-LFeCl2/MAO catalysts and molecular weight characteristics of the PE produced.10]. In accordance with the previously obtained results [7. runs 2.6-Cl2 Yield Kg PE/ mol Fe bar 12650 9100 6650 5800 3) Maximum activity. so the catalysts of this type should be regarded as multiple-site catalysts.102 N.6-i-Pr2 2. Scheme1) are more productive than their aldimine analoges (R = H-. Polymers prepared with the systems (2. producing strictly linear high-molecular weight polymer. Barabanov. Run 1* 2 3 4 Rn 2-Me 2. 3. Scheme1).6-Me2 2. whereas using Al(n-Oct)3 as activator the PE sample with the lowest molecular weight was obtained (Table 1. Semikolenova. run 6). 7-10]. .0 2.6Me2LFeCl2/AlMe3) were characterized by the highest Mw values (Table 1. Modification of the aryl ring attached to the imino nitrogen atoms has the pronounced effect on the catalysts activity and the molecular weight of the produced PE [5. runs 4.6-Me2LFeCl2/Al(i-Bu)3) and (2.7-10]. mol/l. * Only oligomers were obtained. The studied catalysts showed high initial activity that fell with the polymerization time.3 20.6-Me2LFeCl2 and different activators indicate that a set of different active sites is formed in these catalytic systems. for 30 min.6-position of the aryl rings ( R1. and R2. Effect of the Ligand Composition Changes in the ligand environments of iron bis(imino)pyridine complexes results in changes in catalysts productivity and polymer molecular weight [5. [Fe] =1. The catalysts based on iron complexes with a substituent at both ortho –positions of the aryl ring in presence of MAO as activator show high activities for ethylene polymerization. A. Table 2.9 -5 Polymerization in toluene at 35 ºC.6 –position in the aryl ring of the ligand are collected in Table 2 and Fig. As it was shown in [10]. The yield of PE decreases with the increase the substituents R1 and R2 steric bulk because of lower stability of the catalysts formed (Table 2. run 1). 3. 5). 770 500 980 1100 Kg PE/ mol Fe bar min Mw.V. The data on the catalytic behavior of iron bis(imino)pyridine complexes Rn-LFeCl2 bearing different substituents in 2. Echevskaja et al. complexes with a single orthosubstituent on each aryl ring are highly active in oligomerization of ethylene to linear αolefines ( Table 2.4 х 10 MAO/Fe=500.9. The molecular weight of the product depends on the size of the alkyl substiuents in 2. 8 d Wf/ d log[M] 2 0. the PE yield was lower than that obtained with the complex 2. 2H NMR and EPR spectroscopy [12.6-Me2LFeCl3 /MAO catalysts. Though the catalyst (2. curve 4). 38 ]. M=molecular weight). run 4) was found to be less stable.6-Me2LFe(II)Cl2 with the excess of MAO. ( Wf= weight fraction. Catalytic system based on the iron complex bearing electron-attracting halogen substiuents [36] (2. Table 2. Al(i-Bu)3. Linear PE produced with (2. electronic properties of the substituents in the ligand of iron bis(imino)pyridine complexes have the pronounced influence upon their polymerization properties.6-Cl2LFeCl2 /MAO) catalyst was characterized with the lowest Mw and Mw/Mn values (Table 2. the question of how iron(II) catalyst precursors could afford iron(III) catalysts in the presence of such reducing agents as AlMe3 and MAO was not considered). that besides steric effects. that introduction of a halogen substituent into the p-position of the aryl ring results in an increase of the catalysts activity and a decrease in PE Mw value as well [37]. by a comparative study of 2.6-Cl2LFeCl2/MAO) exhibited the highest initial activity. 22-28. . It should be mentioned. MWD of PE produced with homogeneous catalysts 2. The obtained results indicate.0 2 3 4 Log M 5 6 7 Figure 3. i-Pr (3). AlMe3.4 3 0. it was shown that the close precursors of the active centers in both catalysts are ferrous complexes containing iron in +2 oxidation state [24].6-Cl2LFeCl2. the intermediates containing iron in the +3 oxidation state might be formed (however. Later on. Cl (4) (Number on the curve corresponds to the number of the experiment in Table 2).6-R2LFeCl2/MAO: R= Me (2).6-Me2LFeCl2 /MAO and 2.6-Me2LFeCl2. run 4 and Fig 3. The authors of [38] reported that upon interaction of 2. than those obtained using alkyl-substituted complexes.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 4 103 0. Characterization of the “Active Species” The active intermediates of the catalysts based on iron bis(imino)pyridine complexes with different activators (MAO. Al(n-Oct)3) have been studied by 1H . neutral heterobinuclear complexes of the type [LMe Fe(II)Cl(μ-R)2AlR2] or [LMe Fe(II)R(μ-R)2AlR2] dominate in the reaction solution in 2. Barabanov. L. It was found that interaction of 2. formation of new EPR active species was observed: (1) LiPrAlMe2 having signal at g = 2.6-Me2LFeCl2 /MAO systems the ion pairs [LMeFe(II)(μ-Me)(μ-Cl)AlMe2]+[Me-MAO].6-Me2LFeCl2+AlR3 systems.V.6Me2LFeCl2/МАО and 2. For both catalysts the CP values decrease with polymerization time. Al(i-Bu)3) has been studied in more details using 1H and EPR spectroscopy [28]. depending on the activator used (either AlMe3 or Al(i-Bu)3). The available literature data on the reaction of carbon monoxide with a Fe(II) alkyl complexes prove feasible application of polymerization inhibition with 14CO for determination of the Fepolymer chains number (number of active centers) at polymerization over the catalysts based on bis(imino)pyridine complexes of Fe(II).07 and 0. runs 1 and 3). Echevskaja et al. we have used this method to determine the СР and kP values at ethylene polymerization over (2.6-i-Pr2LFeCl2 with MAO and aluminium trialkyls ( AlMe3. Semikolenova. Earlier we have used this method to evaluate CP and kP values for ethylene and propylene polymerization with Ziegler-Natta catalysts [39.40].A.6-Me2LFeCl2/Al(i-Bu)3 catalysts. A. As it was shown in [41]. ion pairs of the type [LFeII(μ-Me)2AlMe2]+[MeMAO]− are formed.003 and (2) another species with a signal at g = 2. Data on the Number of Active Centers and Propagation Rate Constants The data on the number of active centers (Cp) and rate constants of propagation reactions (kP) at olefin polymerization with homogeneous catalysts are of great importance for analysis of the kinetic peculiarities of the reaction and elucidation of factors. carbon monoxide reacts with a Fe(II)-complex of composition С5H5(CO)2Fe(CH3) by inserting into the Fe-CH3 bond.08. When “AlMe3-free” methylalumoxane (MAO (50)) was used as the activator. These ion-pair intermediates are more stable and persist in solution for several hours.(at Al/Fe> 500) were the predominant species [24-27]. The structure of the intermediates was determined from 1H and 2H NMR spectra. presumably of the type L′FeI-Alk where the modified ligand L′ has a singlet ground spin state and iron (I) is low-spin (S = 1/2). This method is based on 14CO insertion into the metal-polymer bond. respectively (Table 3. The observed intermediates were relatively unstable and decayed within minutes at room temperature. Polymerization inhibition by 14CO is a well known method for the determination of the active metal-carbon bonds in the catalytic systems of different types.(at Al/Fe< 200) and [LMe Fe(II)(μMe)2AlMe2]+[Me-MAO]. The obtained СР and kP values are summarized in Table 3. whereas in 2.41 mol/mol Fe for 2. It has been reported that in conditions approaching to real polymerization.104 N.G. Activation of 2. determining the catalysts activity. Thus.6-Me2LFeCl2/MAO) and (2.6-i-Pr2LFe(II)Cl2 with aluminium trialkyls results in one-electron reduction of the former with formation of heterobinuclear complex of the type [LiPr(-)Fe(+)(μ-Me)2AlMe)2] or [LiPr(-)Fe(+)(μ-i-Bu)(μ-X)Al(i-Bu)2] (X = i-Bu or Cl).6Me2LFeCl2/Al(i-Bu)3) catalysts [30-32].5-2 min) were equal to 0. thus causing termination of the polymerization process and formation of labeled polymer. A variety of alkyl complexes of transition metals react with carbon monoxide in the same manner. At the same time. At the initial period of polymerization the reactivity of the examined catalysts (especially 2. The СР values determined at short polymerization times (τpol = 1.6-Me2LFeCl2/MAO) is . 9 7.6-Me2LFeCl2 Run 1) Cocatalyst min. L/mol s Mw × 10-3 Mw/Mn 1 2 3 4 1) MAO – // – Al(i-Bu)3 – // – 1.0 2 3 4 log M 5 6 7 Figure 4.. 14CO/Fe = 21.4 0. CP. runs 1 and 2) and 2.2 0.e. Effect of polymerization duration on the MWD of PE produced with 2.4) at 35 ºC. kP and PE MWD data obtained at ethylene polymerization over the catalysts based on 2. 0. [Fe] = 3-8×10 -6 mol/l.2×104 L/mol·s at 80ºC [42-44]. for comparison.8 9 min 0.6-Me2LFeCl2/МАО and 2.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 105 extremely high (kP = 5×104 L/mol·s at 35ºC). Table 3.6Me2LFeCl2/MAO ( Table 3. Al/Fe = 500. deactivation of 2.5 min 0. τpol. The data presented above allow to suggest that active centers with different reactivity (i. τCO = 5 min.6 d Wf / d log M 7 min 2 min 0.5 – 2 min noticeably decreases as the reaction proceeds.8 b) a) 0. 2) Polymerization rate in the moment of 14СО introduction. Kg PE/ mol Fe mol/mol Fe bar min kР.0 2 3 4 log M 5 6 7 0. with different kP value) are presented in both catalysts 2.6Me2LFeCl2/Al(i-Bu)3. Thus. R2).9 bar.6-Me2LFeCl2/Al(i-Bu)3 catalysts with polymerization time is determined both by lowering of the active centers number and the decrease of the calculated kP value.6-Me2FeCl2/MAO. the kP value of the Ziegler-type catalyst TiCl4/MgCl2/AlEt3 is equal to 1. the centers with high reactivity in the .4 0. runs 3 and 4) (b).1 Polymerization in toluene ( runs 1. runs 3 and 4) the kP value observed at τpol = 1.41 0. ethylene pressure 2.16 49500 15000 26000 8200 44 54 39 66 6.5 9 2 7 600 100 1700 210 0.6-Me2LFeCl2/Al(i-Bu)3 (Table 3.6-Me2LFeCl2/МАО and 2. CP.6 7.6 d Wf / d log M 1. (Table 3. runs 1 and 2) ( a) and 2.6-Me2FeCl2/Al(i-Bu)3 catalysts (Table 3. For both catalyst 2.076 0.039 0.2) or heptane ( runs 3.2 0.2 7. As polymerization proceeds. 2. chain propagation reaction are deactivated first.6-Me2LFeCl2/МАО and 2.6-Me2LCoCl2/Al(i-Bu)3 was almost inactive (Table 4. catalysts with 2. characterizing different active centers present in the system at the time moment. 2. highly active but unstable centers produce the low molecular weight PE. At the initial stage of polymerization. Barabanov.6 –positions of the aryl ring in the ligand of iron complex and of the organoaluminium activator on the Mw and polidispersity (Mw/Mn values) of the resulted PE.4).410.6-Me2LFeCl2/Al(i-Bu)3 catalysts are the average values. 350C). 2. 4 show that contribution of the low-molecular-weight shoulder in MWD curves decreases with the increasing of polymerization time.0×104 L/mol s. correspondently. The ratio of different centers changes with polymerization time. The data of Fig. As apparent from the above. Data on the broad and bimodal MWD of PE. 2) formation of linear PE with high Mw and broad MWD. produced at polymerization over these catalysts (Fig. It should be noted that the increase in PE molecular weight with polymerization time going with simultaneous reduction of the average kP values indicate a sharp decrease in the average rate of chain transfer reactions. Echevskaja et al. This lowering is faster than the decrease of the rate of chain propagation.2 CATALYSTS BASED ON RNLCOCL2 Effect of Activators Table 4 presents the data on the catalytic activity at ethylene polymerization of the Co(II) bis(imino)pyridine complex (2. the values of propagation reaction rate constants calculated for ethylene polymerization over 2. run 4). L.G. 4) formation of the multiple active sites (differing by reactivity and stability in the chain propagation and transfer reactions) in these catalysts upon interaction of RnLFeCl2 with both MAO and aluminium trialkyls and variation of the ratio of these sites in course of polymerization. Like the 2. runs 1.106 N.5 min).04 mol/mol Fe. when activated with the same co-catalysts.6-Me2LCoCl2 exhibited noticeably lower activity than the analogous Fe(II) bis(imino)pyridine complex (Table 1. The detailed analysis of MWD data [32] draw us to the conclusion that at τpol = 1-10 min two types of active centers are present in the studied catalysts.V.6-Me2LFeCl2-based systems.A. the main peculiarities of iron bis(imino)pyridine complexes as an active component of the homogeneous ethylene polymerization catalyst are the following: 1) high activity at activation with different organoaluminium activators and especially with aluminium trialkyls. 5) presence of active centers with very high kp value (≥ 5. A. Semikolenova. 3) noticeable effect of the size and the nature of the substituents at 2. the measured Cp values vary in the range of 0. the values of kP should be higher then the measured average values 5-2. The catalyst system 2. The less active and more stable centers produce PE with high Mw. the proportion of highly active centers is higher and. The results of Table 4 (runs 1-3) show that.6×104 L/mol⋅s. 6) strong effect of catalysts composition and polymerization duration upon the number of active centers. We believe.4) confirm the conclusion on the formation of active centers with different reactivity [30]. but low thermal stability. Thus.6-Me2LCoCl2 as the active . that at the starting moment of polymerization (τрol < 1.6-Me2LCoCl2) with different activators and characteristics of the obtained PE samples. 5. [Co] =1.6-Me2LCoCl2 are shown in Fig. kg PE/ mol Co bar min 1 3 60 4 2) 80 40 2 20 0 10 Time.9 1.AlMe3. min 20 30 Figure 5.8 1.9 1. The time-dependent polymerization activities of the catalysts based on 2.6-Me2LCoCl2 and different activators: (1) . (2) .5 1.МАО(50).8 16 - Content per PE molecule СН3 0.9 1. for 30 min. Table 4. Al/Co=500.0 СН= СН2 0. ethylene pressure 5 bar. (Number on the curve corresponds to the number of the experiment in Table 4). . Kinetic curves for ethylene polymerization over the catalysts composed of 2.6-Me2L Cl2 Run Activator 3) Yield Maximum Kg PE/ activity.0 16.0 16.1 1.9 1. all other conditions were as in runs 1-3 3) Calculated according to Figure 3 4) 13 C NMR data 100 Activity.4×10-5 mol/l.MAO. (3) .0 - 11) 21) 31) 1) MAO MAO (50) AlMe3 Al(i-Bu)3 3100 2700 3600 20 75 100 60 10 1.8 - 15. 2) Polymerization in heptane.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 107 component were inactive at polymerization temperatures above 50ºC.6 - 1. Ethylene polymerization over the catalysts based on 2.2 1. mol Co bar Kg PE/ mol Co bar min Mw × 10-3 Mw/ Mn 4) Content per 1000 С СН3 СН= СН2 15.0 16 - Polymerization in toluene at 35 ºC. Fig 6.6-Me2LCoCl2 /MAO system. curve 3).8 1. ethylene pressure 2 bar.0 2.6-Me2 2. L. 2.8-1. 6.6 -i-Pr2 2-t-Bu 2. Table 4). bearing three Me groups in o. for 30 min ( for run 1 .5-t-Bu2LCoCl2 . In comparison with 2.6-Me2LCoCl2 with different activators only one type of active center is formed. and in contrast to 2. curves 1 and 2). Effect of the Ligand Composition The data about ethylene polymerization over Co bis(imino)pyridine complexes bearing different alkyl substiuents in the aryl rings of the ligand activated with MAO are presented in Table 5 and Fig. demonstrates higher initial activity. at interaction of 2. the catalyst 2-t-Bu-LCoCl2/MAO was less stable. the catalyst based on 2. 1) Calculated according to Figure 5 2) Mv value (intrinsic viscosity data) The values of maximum activity and the rate of catalysts deactivation depend on the ligand composition of cobalt complexes. Kg PE/ mol Co bar min 280 700 150 750 270 Mw × 10-3 1. 5. The catalyst formed by interaction of cobalt complex with AlMe3 was characterized with noticeably higher stability ( Fig. the homogeneous catalysts based on this cobalt complex can be regarded as the single-site catalysts.6-Me2LCoCl2 /MAO (MAO(50)) demonstrate high initial activity that fell with the increase in polymerization time.5 - Polymerization in toluene at 35 ºC.5-t-Bu2 Yield Kg PE/ mol Co bar 2900 5800 1250 4500 6100 1) Maximum activity. causing the increased yield of PE ( Table 5.4.A.5 1.9. 45-47]. whereas the system based on 2. MAO/Co=500. A. 6. runs 1 and 2. As in the case of bis(imino)pyridine iron complexes.6-Me2LCoCl2 and different activators are characterized by low Mw and narrow MWD (Mw/Mn=1. 5. run 1.8 2. its high initial activity sharply fell within some minutes ( Fig.4.6-Me3 2.V.and ppositions of the aryl rings. Effect of the substituents R on the activity of Rn-LCoCl2/MAO catalysts and produced PE molecular weight characteristics Run Rn 2.4 х 10 -5 mol/l. the catalysts 2.15 min) . Fig.108 N. curve 1).6-Me3LCoCl2 complex. The PE samples obtained with homogeneous catalysts composed of 2.6-Me2LCoCl2 activated by MAO demonstrates high initial activity and the highest deactivation rate (Table 4. containing one terminal –CH3 and one –CH=CH2 group per polymer molecule (Table 4). Echevskaja et al. These polymers are extremely linear. Semikolenova.6-Me2LFeCl2.6-Me2LFeCl2. curve 4). Thus. [Co] =1. Barabanov. The values of the initial activity and the rate of deactivation depend on the activator composition. Similar to 2.7 18 330 12002) Mw/Mn 1 2 3 4 5 1. Table 5.G. In accordance with the literature data [10. bearing the only one t-Bu -group in o-position of the aryl ring. 2-t-Bu (4). 2. that narrow MWD of all obtained PE samples indicate that independently of their ligand composition. resulting in the highest PE yield (Table 5.5) and high linearity ( one terminal -CH3 and one -CH=CH2 group per polymer molecule) ( Table 5). Kinetic curves for ethylene polymerization over homogeneous catalysts Rn-PhLCoCl2/MAO: Rn= 2. Runs 1 and 4).Me3 (2). similar to the iron complexes. Mw/Mn= 1. runs 1.4. obtained over 2. min 20 30 Figure 6. The catalyst based on 2-t-Bu-LCoCl2. kg of PE/ mol Co min bar 800 600 1 2 4 400 5 200 10 Time. Introduction of the second t-Bu-group into the ligand results in formation of PE with extremely high molecular weight ( Mv = 1200000.6-Cl2LCoCl2 at 00C Mw=370 g/mol. 2.6-Me2 (1).position of the aryl ring had almost no effect on the Mw and polydispersity values of PE ( Table 5. Run 5). run 5. curve 5). It should be noted.8-2. Characterization of the “Active Species” Recently the nature of the active sites of polymerization formed upon interaction of bis(imino)pyridine cobalt complexes with MAO and aluminium trialkyls was intensively . Thus. the catalysts based on bis(imino)pyridine cobalt complexes retain their single-site character. stability and MW of the produced PE). 3. PE samples obtained with the catalysts RnLCoCl2/MAO were characterized with narrow MWD ( Mw/Mn=1. 5). runs 1 and 2).6. ligand environment in bis(imino)pyridine cobalt complexes has a great influence on theirs polymerization behavior (activity.15) [36]. (Number on the curve corresponds to the number of the experiment in Table 5). Introduction of the third alkyl substituent into the p. The value of PE molecular weight noticeably increased with the increasing steric bulk of the substiuents R ( Table 5.5-t-Bu2 (5).Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 109 displayed quite stable kinetic curve. Cobalt complexes with halogen substituents are approximately an order of magnitude less active than their iron analogues and produce linear PE with very low Mw and narrow Mw/Mn ( for PE produced with 2. produced PE with the Mw value more than 200 times higher than that of polymer. Activity. Fig 6.6-Me2LCoCl2 /MAO catalyst (Table 5. 2. In the initial moment of polymerization over the catalyst 2. LCoIICl2/AlMe3/[CPh3][B(C6F5)4] and LCoIICl2/AlMe3 (where Rn = 2. our 1H and 2H NMR studies of 2.6-Me2LFeCl2. L. studied [12. Barabanov. The obtained data are summarized in Table 6. We have to extend this study to polymerization over the catalysts based on 2-t-BuLCoCl2 and 2. Obviously. Data on the Number of Active Centers and Propagation Rate Constants Data on the values of Cp and kP at ethylene polymerization with the catalysts 2. initial cobalt(II) pre-catalyst reduction to cobalt(I) halide is followed by conversion to a cobalt(I) methyl and ultimately to a cobalt(I) cationic species. According to results of Gibson and Gal.6Me2LCoIICl2/MAO system showed that cobalt(II) complex with proposed structure 2. A.6-Me2LCoCl2/MAO the number of active centers is high ( 23% with respect to total content of cobalt complex) ( Table 6. run 2). and 19F NMR characterization of cobalt(II) and cobalt(I) species formed in the systems Rn-LCoIICl2/MAO. in the LCoIICl2/MAO system. [RnLCoIIMe(S)]+[A]−. that the ion pairs [RnLCoII(μ-Me)2AlMe2]+[A]−.6-Me2LCoCl2/MAO ( 3. addition of ethylene results in the rapid reduction of cobalt(II) to cobalt(I) and only the ion pairs of the type [RnLCoI(S)]+[A]− are present in the reaction solution at 20°C. Addition of ethylene affords an ethylene adduct [LCoI(η2-C2H4)]+[Me-MAO]−. 2H.6-Me2LCoCl2/MAO deactivation with the increase of polymerization time is the reducing of the active centers number.1). 40-42]. In the case of RnLCoIICl2/AlMe3 systems. and [RnLCoI(S)]+[A]− can be observed in the catalyst systems RnLCoIICl2/MAO and RnLCoIICl2/AlMe3/[CPh3][B(C6F5)4] ([A]− = [Me-MAO]− or [B(C6F5)4]−. It was shown.14 mol/mol Co.6-Me2LCoIICl2 and MAO [12 ]. Addition of monomer (C2H4) plays the key role in formation of the direct precursors of the polymerization active centers of the catalysts based on RnLCoIICl2.6-Me2LCoCl2/MAO (2314% with respect to total content of cobalt complex) is noticeably higher than that formed in . In contrast to the catalysts based on 2. whereas neutral complexes RnLCoI(μ-Me)(μ-Cl)AlMe2 and RnLCoI(μ-Me)2AlMe2 predominate in the catalyst systems RnLCoIICl2/AlMe3. S = toluene or vacancy).6-i-Pr2 and 2-t-Bu) was recently undertaken [29].G. the values of propagation rate constant determined for the catalyst 2. The obtained results can explain the close polymerization results (similar activity and PE structure) obtained with the catalyst systems formed by interaction of RnLCoCl2 complexes with MAO and AlMe3. similar intermediates (ion pairs of cobalt(I)) are present in the systems RnLCoIICl2/MAO/C2H4 and RnLCoIICl2/AlMe3/C2H4. The detailed 1H. in the presence of ethylene the ion pair with proposed structure [RnLCoI(η2-C2H4)]+[AlMe3Cl]− is the major cobalt species in the reaction solution.6×103 L/mol⋅s at 350С) were independent of the reaction time.6 ( up to 0. the CP value decreases by a factor of 1.V. 2. run.6-Me3-. With the increase in polymerization time form 5 to 15 min.6Me2LCoIIMe(Cl)(MAO) strongly predominates in the reaction solution at 20°C for at least several hours after mixing 2. in contrast to the catalysts based on bis(imino)pyridine complexes of iron.6Me2LCoCl2/MAO have been obtained by method of polymerization quenching by 14 CO [33. Thus. It should be mentioned that the number of active centers formed in the system 2. the reason of the catalyst 2. Echevskaja et al.6-Me2. In the case of RnLCoIICl2/MAO systems. Table 6. Semikolenova.5-t-BuLCoCl2 complexes. 34].4.A. which is considered as the immediate precursor to the active species [48-50] In contrast.110 N. higher activities of the systems based on t-Bu-substituted complexes in comparison with that of the catalyst 2.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 111 2.9 1.6-Me2-.48 3520 3570 3580 2350 90 100 0.15 min). that the main reaction of polymer chain transfer at polymerization over these catalysts is the reaction of the . k tr . Run 1) Complex min 2. 2.82 - 1..13) Polymerization in toluene at 35 ºC. The values of propagation rate constant determined for 2-t-BuLCoCl2 /MAO and 2.5-t-Bu2-). obtained with 2.6-Me2LCoCl2/MAO in comparison with that of the catalyst based on iron complex is determined by lower propagation rate constants.6-Me2LCoCl2/MAO system (Table 6. 2.5 τpol. [Co] =5 . Kg PE/ mol Co bar min 130 80 520 210 M CP. 3) Polymerization at 500C The data of Table 6 show that PE samples.69 3200 0.4. Mw/Mn and kP values. 0.73 0. Table 6. These results provide evidence. have shown that Mw and Mw/Mn values of polymers are independent of the monomer pressure.5-tBu2LCoCl2 2.5-tBu2LCoCl2 5 15 1 3.6-Me2LCoCl2/MAO.7 1.23. Evidently. So. produced with RnLCoCl2/MAO catalysts (Rn = 2. 14 CO/Co = 13-40.53) 3703) 2. 4).5-tBuLCoCl2/ MAO catalysts were close to that. 2-t-BuLCoCl2 and 2.8 320 - 1.14 0.5-t-Bu2 LCoCl2. τCO = 5 min. kР.t-BuLCoCl2 2.23 0.6-Me2LCoCl2 – // – 2. were a set of active centers is formed and the determined kP is an average value ( Table 3). kP and PE MWD data at ethylene polymerization over the catalysts RnLCoCl2/MAO. Table 3).8 2. are characterized by similar Mw. The reduced polymerization activity of the catalyst 2. The obtained PE samples were highly linear and contain one –CH3 and one –CH=CH2 group per polymer chain.73 mol/molCo correspondingly for Me2LCoCl2 .9 bar.6-Me2LCoCl2/MAO at different polymerization time (5.16×10-6 mol/l. 2) Polymerization rate in the moment of 14СО introduction. Table 6) Study on the effect of the monomer pressure (1-5 bar) upon the molecular weight characteristics of the PE.6-Me32-t-Bu-. runs 3.6Me2LCoCl2/MAO contains only one type of active center and the determined kP value reflects the actual reactivity of these centers.5 270 0. in contrast to the catalysts based on the corresponding iron complex. found for 2. ethylene pressure 2. Mw mol/ L/mol s × 10-3 L/mol s mol Co Mw/Mn 1 2 3 4 0.48 and 0. R2). are accounted for higher numbers of the active centers present in these systems (0.6-Me2LFeCl2/MAO catalyst (8-4%. Al/Co=500. CP. the catalyst 2.7 - 53) 1) 3. chain transfer to monomer. L. This low activity is determined by lower value of rate propagation constants. At 35ºC. inactive at polymerization temperatures above 50 ºC. Table 6. whereas formation of solid PE increases.A. . cobalt bis(imino)pyridine complexes as ethylene polymerization catalysts are characterized by reduced activity in comparison with that of corresponding RnL2FeCl2 complexes.5 L/mol s (polymerization at 500C). curve 1). catalytic systems based on 2. runs 1 and 3). the productivity decreases. 2. thus leading to the increase in the molecular weight of the produced PE. 7. Thus.6-Me2LCoCl2 and 2-t-BuLCoCl2 correspondingly. The value of ktrM depends on the steric bulk of the o-substiuents in the aryl ring of the ligand (ktrM = 90 and 0. The catalysts productivity and properties of the obtained products depend on the substituents in the aryl ring of bis(imino)pyridyl ligand : as the bulk of the alkyl substituents increases.5-t-Bu2 LCoCl2 – based catalyst was found to be 0. they produce highly linear PE with narrow MWD. Increase of PE molecular weight is determined by strong decrease in the value of chain transfer rate constant.V. The value of ktrM for 2. In contrast to the iron and cobalt-based catalysts. [18]. runs 1 and 3). Products obtained with 2. The catalysts formed by interaction of RnLCoCl2 with both MAO and aluminium trialkyls are single-site systems. CATALYSTS BASED ON RNLVCL3 Bis(imino)pyridine complexes of V(III) as active catalysts for ethylene oligomerization and polymerization were introduced by R. It was found that the increased activity of complexes with t-Bu-substituents is determined by an increase in the number of active centers with the same kP value. The bulk of the substituents at the o –positions of the aryl ring in the ligand of cobalt complex greatly affects the activity and the Mw values of the PE produced.6-Et2LVCl3 were highly active at 60 ºC (Table 7.82 L/mol s for 2. Echevskaja et al. polymerization at 350C. On the basis of the obtained experimental data the values of chain transfer rate constants (ktrM ) were determined (Table 6). 2. Barabanov.6substituted complexes consisted mainly of solid polymer.6-Et2LVCl3 activated with commercial MAO.G.6-Et2LV(III)Cl3 was used to study the effects of polymerization temperature and activators upon the catalysts properties at ethylene polymerization. The obtained results are collected in Table 7 and Fig. Bulky substituents at the o-position of the aryl ring of complex ligand hinder the reaction of chain transfer.al. 7. Effects of Polymerization Temperature and Activators 2. was characterized by lower activity but the stable kinetic curve (Fig. and with the increase of the substituents bulk the value of ktrM decreases. Semikolenova. Schmidt et. In presence of MAO as activator productivities of vanadium complexes varied from 3×103 to 580×103 kg PE/mol V for 30 min at reaction temperature 600C and ethylene pressure 250 psig.112 N. A.3. 01 M of AlMe3) .6 Et2LVCl3 Run Activator T °C min τpol.4 2.0 СН=СН2 ‐ ‐ 1. Kg PE/ mol V bar min 170 350 360 260 Mw × 10-3 Mw/Mn 3) Content per 1000 С СН3 СН=СН2 4.2 - MAO(20) Polymerization in toluene at ethylene pressure 2 bar.7 5 12 - 2. Ethylene polymerization over the catalysts based on 2. [V] =1.1 4. 1) 2) Yield Maximum activity.Table 7.2 - Kg PE/ mol V bar Content per PE molecule СН3 ‐ ‐ 1.8 - 4.4 ×10 mol/l.0 - 1 2 3 4 1) 2) MAO MAO MAO 4) 35 60 60 60 30 4 30 30 3300 3250 11000 6500 -5 6. Calculated according to Figure 4 3) 13 C NMR data 4) MAO sample with reduced content of AlMe3 (~ 0. Al/V=500. A. (1) –polymerization at 35 °C.G. 7. but with the increase in polymerization times polydispersity of PE increases (Table 7. which rapidly fell with the polymerization time. (3) – polymerization at 60 °. Evidently. Reducing the free AlMe3 content in MAO samples (MAO(20)) used for activation of vanadium complex (Table 7. The samples (2. 400 Activity.6-Et2-LVCl3/MAO showed high initial activity (Fig. PE prepared with the catalysts 2. (Number on the curve corresponds to the number of the experiment in Table 7). Increase in the polymerization temperature up to 60 ºC resulted in formation of PE with narrow MWD at short polymerization time (Mw/Mn=2.6-Et2LVCl3 +MAO) display broad unresolved NMR and EPR spectra that hinder the assignment of the signals. (Table 7). run 3. Kinetic curves of ethylene polymerization over 2.114 N. kg PE/ mol V bar min 300 3 200 100 1 0 10 Time. As a result. Mw and Mw/Mn values of the produced PE increase with time. L. Semikolenova. . Barabanov.4) was obtained in polymerization run at 35 ºC (Table 7. run 4) led to the decrease of the initial activity and of the PE yield. curve 3). min 20 30 Figure 7. In polymerization runs at 60 ºC the catalyst 2.1. PE with narrow MWD (Mw/Mn =2.V.6-Et2LVCl3 was inactive.6-Et2LVCl3 /MAO .6Et2LVCl3 with MAO at the temperature 600C generates unstable centers of the only one type. interaction of 2. These centers are responsible for the formation of PE with low Mw and narrow MWD at the beginning of polymerization. 2. As the polymerization proceeds. Table 7.8). run 2). run 1). at τpol = 4min. The value of PE polydispersity depends on the polymerization conditions (temperature and polymerization time). In the presence of MAO completely purified from free AlMe3 (MAO(50)) or with AlMe3 as activator. Mw/Mn=4. the new centers which produce PE with higher Mw are formed. The nature of the active species formed upon interaction of RnLVCl3 with MAO remains unclear. Echevskaja et al.A.6-Et2LVCl3 /MAO) displayed high linearity and low Mw. 9 Polymerization in toluene at ethylene pressure 2.6-2. The obtained results are shown in Table 8.18 0. runs 2 and 4 and Fig. depend on the steric bulk of the substituents in 2. MW of PE produced with 2.5 11 3. obtained with vanadium bis(imino)pyridine complexes. curves 1 and 3). runs 2 and 4).6Et2LVCl3 – // – – // – 2. Kg PE/ mol V mol L/ mol V s bar min /mol V Mw. МАО/V = 500-700. In both cases PE with narrow MWD (Mw/Mn = 1.1 1.4-0.42 2580 16430 6380 19900 5.1) Complex T.21 ×10-6 mol/l. prepared using the system based on 2. 14CO/V = 14-22.6-Me2LVCl3 is determined by formation of close number of active centers (Cp = 0.50 0. With the increase in polymerization temperature up to 60oC.6-Me2LVCl3 ( Table 8.6-Et2LVCl3 /MAO at this temperature. The values of Cp and kP found for 2.6-Et2LVCl3 /MAO and 2. τCO = 5 min. indicating that at activation of vanadium bis(imino)pyridine complexes with MAO only one type of active centers is generated.2 4. C 0 min τpol.7 5.6Me2LVCl3 /MAO at 35 and 600C.6-Et2LVCl3 /MAO catalyst at 350C ( Table 8. Al/V=500. runs 1 and 2).9 bar. activity of the vanadium based catalysts noticeably increases due to the increase in both the active centers number and kP value ( Table 8. Table 8.5 mol/mol V) with similar reactivity (kP = 1. . The molecular weight of the polymers.6-Et2LVCl3 and 2.3 2. based on iron and cobalt bis(imino)pyridine complexes (Tables 3 and 6).0×104 L/mol s) (Table 8.5 2. kР.6Me2LVCl3 35 60 60 60 5 2 19 3 90 870 210 880 0.31 0. CP. CP. 2) Polymerization rate in the moment of 14СО introduction.6 R2LVCl3 complexes Run. [V] =14 . run1) are lower than those for the catalysts. kP and PE MWD data at ethylene polymerization over the catalysts based on 2.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 115 Data on the Number of Active Centers and Propagation Rate Constants The method of polymerization quenching by 14CO was applied to determine the Cp and kP values for ethylene polymerization over the catalysts 2.9 – 2. 8.6-Et2LVCl3/MAO catalyst is somewhat higher than that of polymer. being the reason of the lower activity of 2. Similar activity exhibited by the catalysts based on 2.2) was obtained. R2). Mw/Mn × 10-3 1 2 3 4 1) 2.6-position of the aryl rings of the ligand. 2.4 3 0. (Number on the curve corresponds to the number of the experiment in Table 8). At high temperature (60 °C) they act as a single-site catalysts only at a short polymerization times. producing high molecular weight PE appear in the system and initially single-site catalyst 2. In this case (Table 8. but as the polymerization proceeds they turn into multi-site catalysts.0 1 2 3 4 log M 5 6 7 4 Figure 8. It was shown that upon activation of RnLCrCl3 with MAO the catalysts highly active at the increased d Wf / d log M . MWD of PE produced over RnLVCl3/MAO catalysts at 600C: (2) Rn = 2. It was found that deactivation of the catalyst with polymerization time is caused by lowering of both the number of active centers and the value of propagation rate constant. (4) Rn = 2. i-Pr.4. Probably. Et.G. the determined reaction rate constant is an average value.6-Et2-. L. curve 2). vanadium bis(imino)pyridine complexes are effectively activated only with MAO Reduction of the free AlMe3 content in MAO reduces the catalytic activity of RnLVCl3/MAO system. polymerization for 19 min. (3) Rn = 2. Thus. PE sample obtained at longer polymerization time was characterized by the increased Mw value and broadened MWD due to formation of a high-molecular weight PE fraction ( Fig. Semikolenova.8 0.6-Et2LVCl3/MAO was studied ( Table 8. Effect of the reaction time upon the Cp and kp values at polymerization over the catalyst 2. characterizing different active centers present in the system at the time moment. run 3). Active centers formed by interaction of RnLVCl3with MAO demonstrate higher thermal stability in comparison with those of RnL2FeCl2 and RnLCoCl2–based systems. 8. Echevskaja et al. the catalyst activity noticeably decreases.al [19].0 0.A. Catalysts Based on RnLCrCl3 A family of chromium (III) bis(inino)pyridine complexes (RnLCrCl3. Barabanov. A. t-Bu) was synthesized and tested in ethylene polymerization by Esteruelas et.2 1.2 0. Rn= H.6 0.116 N.6-Me2-.6Et2LVCl3/MAO should then be regarded as a multi-site one. As polymerization proceeds from 2 to 20 min. polymerization for 3 min. The catalysts RnLVCl3/MAO act as a single-site systems at low polymerization temperatures (35°C). 2 1. polymerization for 2 min. runs 2 and 3). Me.6-Et2-. at longer polymerization times new active centers.V. preactivation with MAO at 250C. In contrast to the previously described catalysts based on iron. The effective method to form the active component of these catalysts via preliminary interaction of 2.4. MAO/Cr= 200 ( polymerization at 70 °C. These catalysts produce highly linear polyethylene.polymerization without preactivation ( polymerization at 70 °C and 5 bar of C2H4 .preactivation with MAO (50) at 250C. (Number on the curve corresponds to the number of the experiment in Table 9). . at 5 bar of C2H4. 9. Al(i-Bu)3 /Cr=1000). [19]. Complexes with two o-substituents proved to be more active catalysts than those.6-Me3LCrCl3 at various preactivation mode and polymerization temperature: (1) . at polymerization with this catalyst a long period of acceleration is observed.6-Me3LCrCl3) activated with MAO. with Al(i-Bu)3. The highest activities were achieved with the catalysts based on Cr(III) complex with Me substituents in both o. (4) . and in line with the results of ref. min 40 50 60 Figure. in heptane.preactivation with MAO at 250C.position of the aryl ring. MAO/Cr= 200 ( polymerization at 70 °C. whereas the molecular weight of the produced PE increases. Al/MAO=500). with Al(i-Bu)3 . kg PE/mol Cr bar min 2 300 6 200 1 100 4 0 10 20 30 Time. The substituents at the o-position of the N-aryl groups affected both catalytic activity and molecular weight of the resulting PE.and pposition of the aryl ring (2. bearing one alkyl group in the o. in heptane. Kinetic curves for ethylene polymerization over 2. cobalt and vanadium complexes. 400 Activity.4. in heptane. Effect of Activators Figure 9 (curve 1) shows the kinetic curve of the ethylene polymerization at 70°C over chromium(III) bis(imino)pyridine complex (2. Al(i-Bu)3 /Cr=1000).4.6-Me3LCrCl3 with MAO solution at low molar ratio of the components (AlMAO/Cr=100-200) was suggested in ref. (2) . [19]. at 5 bar of C2H4. Al(i-Bu)3 /Cr=1000).Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 117 polymerization temperatures (700C) are formed. (6) . A thus prepared solution of the chromium complex is very stable and could be used for ethylene polymerization at 70 °C in heptane with Al(i-Bu)3 as an additional co-catalyst. in toluene with MAO as co-catalyst. MAO/Cr= 200 ( polymerization at 35 °C. The increase of steric bulk of the substituents causes a decrease in the catalytic activity.4.6-Me3LCrCl3 ). at 5 bar of C2H4. with Al(i-Bu)3. ethylene pressure 5 bar.0 3.5 1. ethylene pressure 5 bar. 3) Polymerization at 35ºC.0 17.0 5.0 - 0.2 1.97 0.9 0. ethylene pressure 5 bar.7 1.3 1.4. co-catalyst MAO (AlМАО/Cr=500) Polymerization in heptane at 70ºC. for 60 min. co-catalyst Al(i-Bu)3 (Al(i-Bu)3/Cr =1000).2 - 15. 4) Molar ratio Al/Cr =200 5) Calculated according to Figure 9 6) 13 C NMR data .6-Me3LCrCl3 Run.8 - Polymerization in toluene at 70ºC.6 16.0 5.0 4740 7880 9680 9920 2870 12400 1. Kg PE/ mol Cr bar min 140 330 400 360 300 260 Mw × 10-3 Mw/Mn 6) Content per 1000 С СН3 СН=СН 2 Content per molecule СН3 0.1 1. co-catalyst Al(i-Bu)3 (Al(i-Bu)3/Cr=1000).3 5.9 1. for 30 min. for 30 min.0 5.9 1.9 17. 4) 5) Pre-activator [Cr] µmol/l Yield Kg PE/ mol Cr bar Maximum activity. Effect of preactivation mode on the ethylene polymerization activity of 2.Table 9.9 - PE СН=СН 2 11) 22) 32) 42) 52) 63) 1) 2) MAO MAO (20) MAO (50) MMAO MAO 20. 2÷1. run 2). depending on the nature of the co-catalyst used. Data in Table 9 and Fig.4. Apparently.5 times higher than that. due to coordination of aluminium trialkyl on the active center) with formation of so-called “dormant” centers.6-Me3LCrCl3 with MAO at the molar ratio AlMAO/Cr =200.5 min) was noticeably higher (Cp= 0. the polymerization starts immediately with high activity (Fig. curve 1). runs 1 and 3). the catalyst 2.4. curves 2 and 6). Catalytic systems based on 2.6-Me3 LCrCl3/MAO/Al(i-Bu)3 produces PE with narrow MWD. Table 10.4. Data on the Number of Active Centers and Propagation Rate Constants Table 10 represents the data on the number of active centers and their reactivity for ethylene polymerization at 35 and 700C with 2. Table 9) due to the higher stability of the catalyst at lower polymerization temperature.6-Me3LCrCl3/activator (where activator was MAO. τpol= 3. The Cp value determined at the increased polymerization temperature (700C . the activation of 2. in course of polymerization on the active centers of the catalyst temporary interruption of polymer chain propagation reaction can occur (for example.36 mol/mol Cr). The increase in the PE MW at higher polymerization temperatures seems to be unusual.9) and close Mw values (1.5×103) (Table 9. run 1). runs 2-4). In accordance with that.6-Me3 LCrCl3/MAO/Al(i-Bu)3 revealed high initial activity at increased polymerization temperature (70 ºC ) which rapidly fell with the increase in polymerization time. (Figure 9.4. proving that only one type of active center is formed in this system. whereas the reactivity of these centers is relatively low ( (kp= 1400 L/mol s. obtained in polymerization at 70 ºC (compare runs 2 and 6. The EPR studies of the catalyst systems 2.6-Me3LCrCl3 with MAO leads to formation of the active centers via the reduction of Cr(III) to a lower oxidation state. In agreement with the literature [19. curve 2) providing higher PE yield in comparison with that of the system without preactivation (Table 9.4. Probably. The initial signals of Cr(III) disappeared within 5-30 min. Therefore the yield of PE obtained in polymerization run at 35 ºC for 30 min was 1. To explain these contradictions the following considerations can be suggested. preactivated by different samples of MAO produce highly linear PE with narrow MWD (Mw/Mn = 1.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 119 In the case of pre-activation of 2. It is possible to assume that the time of “dormant” state of the active .7÷1. These spectra are characteristic of S = 3/2 chromium(III) complexes [51].4. because it is well known that the increase in polymerization temperature leads to the decrease in molecular weight of polymers. At 350C and at a short polymerization time (τpol = 4 min) the number of active centers formed in the catalytic system is rather high ( 0. determined using the method of polymerization quenching by 14CO.76 mol/mol Cr). MMAO) have shown the appearance of EPR spectra after mixing the reagents. recently synthesized bis(imino)pyridine complexes of Cr (II) [52] and complexes containing Cr in formal monovalent oxidation state [53] proved to be highly active at ethylene polymerization in the presence of MAO. 9 show that the preactivated systems 2. 9.6-Me3LCrCl3/MAO/Al(i-Bu)3 catalyst.35].10. Lowering of the polymerization temperature results in a shift of the PE MWD curve to the low-molecular weight region ( Fig. With the increase in polymerization temperature the kP value also increases up to 3430 L/mol s (Table 10.6-Me3LCrCl3.4. Barabanov.6-Me3LCrCl3/MAO/Al(i-Bu)3 catalyst at different polymerization conditions: (1) 350C. L/mol s Mw × 10-3 Mw/ Mn 1 2 1) 4 3 35 70 80 260 0. L. C Rb). Al(i-Bu)3/Cr =1000.4.5 Polymerization in heptane at ethylene pressure 3 bar.4. 2) Polymerization rate in the moment of 14СО introduction. The active centers of these systems provide high PE yield in polymerization at 70 °C.5 0. A.4. Semikolenova. 4 min.0 1 2 3 log M 4 5 Figure 10. 14 CO/Cr = 17-22. kP and PE MWD data at ethylene polymerization with the catalyst 2.6Me3LCrCl3 with MAO produce only one type of active centers and the catalysts of this type can be regarded as single site catalysts.6-Me3LCrCl3/MAO/Al(i-Bu)3.8 1. The number of active centers formed at the initial .5 d Wf / d log M 2 1.76 1410 3430 0. [Cr] =0. evidences that interaction of 2.0 1 1. Run 1) min τpol.4. The CP.A.120 N.6Me3 LCrCl3 can be formed only in presence of MAO. resulting in formation of polymer with the increased MW. mol/mol Cr kР . (2) 700C.2 1. Table 10. (Number on the curve corresponds to the number of experiment in Table 10). 0 T. MWD of PE produced over 2. Echevskaja et al.G. centers decreases with the increase of polymerization temperature. the obtained data show that the active component of the catalysts based on 2.6-Me3LCrCl3/MAO) /Al(i-Bu)3. 3 min.4. 2.3 1.36 0. Kg PE/ mol Cr bar min CP. Thus.V.5-1×10-6 mol/l. Narrow MWD of PE samples obtained with the systems (2. τCO = 5 min.0 0. 4×103 L/mol s at 350C ) 3. In comparison with the well known catalyst based on zirconocene complex [50]. vanadium and chromium bis(imino)pyridine complexes display very low copolymerization ability. Table 11.6-Et2LVCl2/MAO MAO/V=500 2. The catalysts (2.4 400 Me2Si(Ind)2ZrCl2+ MAO 60 25 Co-monomers molar ratio in the polymerization medium Bu-branching content in the obtained polymer (13С NMR data) 3) Data of ref.0 4.Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 121 moment of polymerization at 700C is high ( 0. Ethylene /1-hexene copolymerization with homogeneous catalysts based on bis(imino)pyridine complexes Catalyst 2. the r1 values found for iron.0 2.6Me3LCrCl3/MAO)/Al(i-Bu)3 are characterized by low reactivity at propagation reaction ( the kP value is 1.6-Me3LCrCl2/MAO/Al(i-Bu)3 MAO/Cr=200 Al(i-Bu)3/Cr = 1000 3) 1) 2) T.6-Me2LFeCl2/Al(i-Bu)3 Al/Fe=500 2.8 r1 >1000 200 70 2. . Data on ethylene copolymerization with 1-hexene promoted by catalytic systems based on bis(imino)pyridine complexes of Fe(II). V(III) and Cr(III) are presented in Table 11. and [Cα]/[C2H4]react is the molar ratio between the concentrations of the co-monomers in the reaction medium [54].2 3. [55] The copolymerization parameter r1 was determined using the simplified copolymerization equation ([Cα]/[C2H4]pol = 1/r1[Cα]/[C2H4]react) where [Cα]/[C2H4]pol is the molar ratio between the units of 1-hexene and ethylene in the copolymer.2 2) Bu / /1000 C < 1. The obtained results indicate that catalytic systems based on iron.4. but these centers are very unstable and are rapidly deactivated with polymerization duration. ETHYLENE-1-HEXENE COPOLYMERIZATION OVER THE HOMOGENEOUS CATALYSTS BASED ON BIS(IMINO)PYRIDINE COMPLEXES An important property of polymerization catalysts is their ability to control the molecular structure of the growing polymer by the copolymerization of ethylene with α-olefins. vanadium and chromium complexes were noticeably higher (Table 11).4.76 mol/mol Cr). °C 35 60 1) [C6H12]/ [C2H4] 3. 6 2. (3) formation of multiple active sites and transformation of the active centers in the course of polymerization. Comparison of bis(imino)pyridine complexes as homogeneous catalysts for ethylene polymerization Catalyst 2.6 → 12 1.8 1.6-Me2LFeCl2 are characterized by (1) very high activity at low polymerization temperatures (35 °C) with different activators (both MAO and aluminium trialkyls).4 3.7 35 50 35 60 35 70 1) Mv value (intrinsic viscosity data) It is evident.5 → 11 0.18 0. Interaction of 2.48 0.36 0.7 5. Barabanov.8 320 1200 1) 370 5.41→0. A.76 kp ×10-3 L/mol·s 49 → 15 3.69 0. characterized by (1) relatively low activity and low thermal stability.5 2.2 Mw/Mn 4. Table 12.8 2. that the catalytic behavior of bis(imino)pyridine complexes with close composition of the bis(imino)pyridyl ligands essentially depends on the transition metal center. (2) low thermal stability of the active sites.5 → 6.3 1.1 1.7 2. L.G. (2) PE with low Mw and narrow MWD is produced with the catalysts based on 2.14 0.6 16.4 Mw· × 10-3 44 → 115 1.6-Me2LFeCl2 (MSC) 2. (4) formation of linear PE with high Mw and broad MWD.6-Me2LCoCl2 (SSC) 2-t-BuLCoCl2 (SSC) 2. (5) the reduction of catalysts activity with polymerization time is caused by decrease in the number of active centers and their reactivity with polymerization duration. C 35 35 35 Rp kgPE/mol M·min·bar 1700 → 100 130 → 80 520 100 210 90 870 → 210 80 260 Cp mol/mol M 0.6-Et2LVCl3 (SSC → MSC) 2.4 3.122 N. The catalysts based on 2. Echevskaja et al.31 0. whereas their reactivity remains constant.A.73 0.6 3.5-t-Bu2LCoCl2 (SSC) 2. Semikolenova. (3) deactivation of the catalysts in course of polymerization is connected with the reduction of the number of active centers.1 2.6-Me2LCoCl2.2 → 4.V. (4) the molecular weight of the produced PE is greatly affected by the size of the substituents at the o –positon in the .4.039 0.3 1.6Me3LCrCl3 (SSC) o T.6-Me2LCoCl2 with different activators produces only one type of active site.50 → 0. CONCLUSION The data presented above on the ethylene polymerization activities at different temperatures for bis(imino)pyridine complexes with different transition metal center and the Cp and kp values together with the data on Mw and MWD of the produced polymers are summarized in Table 12.2 2.23 → 0. 6Me2LCoCl2 because of different stabilities of these catalysts (Table 12).6-Me2LCoCl2. V(III) and Cr(III) generate single site catalysts.4. resulting in broadening of MWD of the resulted PE.0. it can be regarded as a single site catalyst producing PE with narrow MWD. the catalysts activity sharply decreases. Only one type of active center is formed in the systems (2. in the catalysts based on RnLVCl3 in the course of polymerization simultaneously with the deactivation of the initially formed highly active centers. The Mw values of PE are mainly determined by the substituents in the aryl ring of bis(imino)pyridyl ligand. bis(imino)pyridine complexes of Co(II). producing PE with low Mw and narrow MWD at polymerization temperatures at 35-700C. Thus formed catalyst is highly active within the broader temperature range (35-60 °C). but with the increase of polymerization time the initial active centers are deactivated ( the Cp value decreases) and new multiple active sites are formed in the system. Activity of these catalysts depends on both the number of active centers and the value of propagation rate constants.6-Et2LVCl3> 2. The centers appear in course of polymerization are less active than the initial ones and produce PE with higher MW. Thus.6-Me2LCoCl2 ≈2.6-Et2LVCl3 is activated only upon interaction with MAO. whereas Mw and Mw/Mn values of the produced PE increase.6-Me3LCrCl3/MAO/Al(i-Bu)3.76 . whereas the values of PE yield forms another order: 2.4×103 L/mol s. 2. the yield of PE depends on the stability of these centers ( the decrease in Cp values with polymerization time). This catalyst acts as a single site in the initial period of polymerization ( 5 min).6Me2LFeCl2» 2. As a result. 350C) and rather low and similar for the complexes of Co.6-Me2LFeCl2 >2. Iron and cobalt-based systems are inactive at the temperatures higher than 50 °C. 350C).6-Me2LFeCl2> 2. V and Cr (3. producing PE with narrow MWD. The kp values are very high for the catalysts based on the iron complexes ( 50-15×103 L/mol s.4.6-Et2LVCl3 ≈ 2. RnLVCl3 and RnLCrCl3 is formation of multiple active centers upon interaction with activators of different types: MAO or AlR3.6-Me3LCrCl3 are formed upon interaction of chromium complex with MAO at low MAO/Cr molar ratio. temperature. Highly active catalysts based on 2. the measured catalysts reactivity decreases whereas the Mw value of the produced PE increases and MWD broadens. The main difference between RnLFeCl2 catalysts and the catalysts based on RnLCoCl2 .6-Me3LCrCl3 >2. At low polymerization temperature (35 °C). .Homogeneous Catalysts Based on Bis(imino)pyridine Complexes … 123 aryl ring of bis(imino)pyridyl ligand due to profound effect of these parameter on the transfer reaction constant. new active centers appear.6-Me3LCrCl3> 2. However.4. activator) and varies within a broad range (0.6-1. At higher polymerization temperatures (60 °C) the polymerization kinetics for this catalyst becomes more complex: during the polymerization. Additionally. The number of active centers depends on polymerization conditions ( duration. however the transition metal also affects the PE molecular weight: the Mw values of PE produced at 35 °C decrease in the order 2.4. Comparison of the catalytic properties of bis(imino)pyridine complexes with similar ligand framework has shown that in polymerization runs at 35 °C the value of maximum activity decreases in the order 2.6-Me3LCrCl3.6-Et2LVCl3> 2.04 mol/mol M).4. The active centers of the catalysts with RnLVCl3 and RnLCrCl3 as active component are noticeably stable and these systems exhibit high initial activity at 60-70 °C. .L. ACKNOWLEDGMENTS The authors are grateful to Prof. J. V. 4375-4386. 222. J. G.. Small... 283-315. Yang. Semikolenova. 24... Echevskaja et al. 2007. Fan. Solan. D. Britovsek. B. D. Gibson.Catal.P.. L. I.C.. V.C.G. 395-406. Welch. Brookhart.J. Sogo. G. Am. A. J. Soc.P. Yashida. 2000.M. Sh. Waymouth.... H. Williams. Rapid Commun.M.. 210.M.. Rapid Commun. H..Chem. Mendez. 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Gambarotta. 28652874 . Y..3945. Gibson. B. O’Rourke. Barabanov. J.A. M. V.. .. Q.. Carney. Scott.V.E. Gibson. Angew.. V. 107. J. Holman. 24. P.. [48] Kooistra.V. 2263-2265. M.. 2002. L. Chem. C. D.. C.126 N. [55] Kaminsky.S. 2005. Li. Rev..P. 3201-3211. Semikolenova.. Li. Tellmann. 1991. Faculty of Chemical Technology Institute of Chemical Technology Prague Technicka 5. due to immense possibilities of the catalyst and substrate structures. The plethora of fine chemical products available on the world market indirectly demands constant improvements in the production processes and literally dictates an individual. the stereoselectivity of the reaction. * Corresponding author: Phone: +420 220 444 214. Ir). i.e. Although this chapter focuses on Ru catalysts. While only a few metal centres can be used effectively (namely Ru. Therefore. Much like enzymes. 166 28 Prague 6. E-mail: libor.cz. the objective is to synthesize only those truly offering the desired behaviour. the auxiliary ligands offer infinite solutions of key changes to the structure. Fax: +420 220 444 340. . In the field of asymmetric chemistry. The relentless expansion of the product range thus demands rapid but reliable tools for finding the optimal reaction conditions for a synthesis of the chiral product in question. Naturally. Poehler ISBN: 978-1-61122-894-6 © 2011 Nova Science Publishers. almost every reaction requires at least a slightly modified catalyst or reaction conditions. an additional yield requirement arises. there is no catalyst to suit all substrates. Chapter 4 RATIONAL DESIGN OF CHIRAL RUTHENIUM COMPLEXES FOR ASYMMETRIC HYDROGENATIONS Jiří Václaví
[email protected]: Homogeneous Catalysts Editor: Andrew C. The rational design has become a well-known term to describe the process of fine-tuning the ligand. Petr Kačer and Libor Červený* Department of Organic Technology. Czech Republic INTRODUCTION Thorough optimization of reaction conditions for maximum yield is the essential prerequisite of every reaction conducted on an industrial scale. Rh complexes are also mentioned. Os. Trial-and-error syntheses and subsequent testing of all (at first sight) potentially effective catalysts are as costly and time consuming as traditional combinatory methods. Rh. made-tomeasure solution for the best efficacy. Inc. Many of the complexes prepared by these laborious procedures finally prove ineffective when trying to utilize them in a stereoselectively catalyzed reaction. the branch of asymmetric synthesis might not exist to the contemporary extent at all. enabling us to refine the search results by stepwise reduction of the number of potentially successful catalysts by employing more sophisticated techniques.128 Jiří Václavík. it ought to be noted that empirical findings still maintain an inimitable and supreme role. discovered the monophosphine CAMP ligand 2 [4] which enabled a comfortable synthetic procedure of L-DOPA. allylic alkylation. Petr Kačer and Libor Červený owing to the high parallelism of these two coordination centres in the field of asymmetric hydrogenation. some of these are mentioned as explanatory references that may be applied to all ligands. Occasionally. either by high-throughput experimentation (HTE) techniques. hydrosilylation etc. If it were not for the first phosphorus-based ligands. well aware of this ultimate discovery. however.e. are not covered. This process involves a competent rejection of structures with a significant potential of failure with regards to enantioselectivity. The origins of successful chiral ligands date back to 1971 when Kagan and Dang introduced the bisphosphine chelate DIOP 1 [3] possessing C2 scaffold chirality. Given the vast number of possibilities. Nowadays. or through computational chemistry. such a process would ideally be performed automatically. Bearing in mind the structure of the chiral product. which have been amply reviewed [1] and are not covered within this chapter despite their rapid development in recent years. [2] The most important ligands. Nonetheless. hydrocyanation. including those for hydrogenation. The term “rational design” comprises the practice of altering the molecular structures aided by computational modelling. HISTORICALLY IMPORTANT CHIRAL LIGANDS Phosphorus – A Foundation Stone of Asymmetric Synthesis The aim of this chapter is to outline the progression in asymmetric catalysis involving phosphorus. This preliminary virtual assay is often referred to as in silico screening. the reader is advised to note that this chapter concentrates on those used in asymmetric hydrogenation. Nevertheless. as this ligand class undeniably belongs to the most important compounds used for reduction of prochiral alkenes and ketones in particular. an experienced theoretical-organic chemist should be able to assemble a well-founded series of ligands offering good possibilities of achieving the desired performance in a particular situation. Recently. readily developed a structural analogue DIPAMP 3 [5] which was soon synthesised on an . Computational methods on various levels of complexity are available. reductive amination. i. high-capacity virtual ligand libraries have been created and analyzed. Knowles. which formed the very foundation depicting the development in this field within the past decade. Molecular modelling is doubtless a powerful tool but one needs to appreciate that even models of the highest accuracy are still an approximation and will never yield 100% match.. there are thousands of ligands used in asymmetric syntheses and millions of further possibilities. the most extensively-used drug for clinical treatment of Parkinson’s disease. Knowles et al. Independent of this work. are presented below. Ligands used for asymmetric hydroformylation. allowing a systematic description of existing ligands and a subsequent prediction of the properties of analogues. The true rationale behind this advancement was a path-breaking metal-ligand bifunctional mechanism [11] which did not require the substrate to bind to the Ru centre directly. [9] α-tocopherol. and could thereby proceed without the need for the substrate to contain Ru-coordinating structures. in particular carbapenem [8] and levofloxacin antibiotics. The pioneering phosphorus chiral ligands. This synthesis was successful only thanks to the persistence of the Noyori group as their discovery was preceded a 4-year search for the best procedure. [8] The introduction of this bisphosphine ligand (Figure 2) substantially extended the range of alkenes possible to hydrogenate. the new system allowed a convenient synthesis of a potent antidepressant (R)-fluoxetine.. the diamine being DPEN or DAIPEN. all of these being widely-used pharmaceuticals. still remained unapproachable due to the lack of Ru-binding heteroatoms in the substrate structure. reduction of functionalized ketones afforded valuable products. In 1980. The ferrocenyldiphosphine JosiPhos 9 type of ligand. thus optimizing the structure of the ligand to serve a particular substrate.Rational Design of Chiral Ruthenium Complexes … 129 industrial scale – the famous Monsanto L-DOPA synthesis. Additionally. many analogues emerged which are mentioned further in the text. [6] Incorporated in a Rh complex.R)-DIPAMP 3 Figure 1. developed by Togni et al.R)-CHIRAPHOS 4 (R. [8] Interestingly. . [12] In 1991. For example. O O P PPh2 PPh2 P MeO Me P OMe PPh2 PPh2 (R. BINAP is able to operate both on RhI and RuII coordination centres. belonging to the bis(phospholane) group. Burk [13] added BPE 7 and DuPhos 8 to the expanding ligand collection for prochiral alkene reduction using Rh catalysts. were the first representatives possessing the rigid phosphocyclic structure which proved to be very powerful in terms of enantioselectivity of the complex. Fryzuk and Bosnich prepared a very simple yet potent C2-symmetric diphosphine CHIRAPHOS 4. morphine or dextromethorphan. not many monodentate ligands had emerged by 2000. [14] demonstrated the possibility of applying various substitutions to the phosphorus atoms. to name the most significant.. a huge step forward was made by Noyori et al. CHIRAPHOS proved very selective in α-N-acylaminoacrylic acids hydrogenation. Selective catalytic hydrogenation of simple ketones. These ligands (Figure 3). namely the noteworthy syntheses of naproxen. since their introduction. This only became possible after the introduction of the RuII XylBINAP-diamine and TolBINAP-diamine systems [10] (6 in Figure 2).R)-DIOP 1 OMe CAMP 2 (R. These two ligands prosper from phosphorus atom chirality and surprisingly. [7] who presented the axially chiral BINAP ligand 5. As a result. however. In 1977. yet with the opposite stereoselectivity owing to different reaction pathways. The advantages of Rh catalysts bearing monodentate ligands comprise mainly high modularity and straightforward syntheses from cheap precursors.R)-DPEN}] Ar = 3. BINOL-derived monodentate ligands [15d] (Figure 4) bring a new approach. respectively (10a. Bis(phospholane) and ferrocenyldiphosphine ligands. the real boom in this area started as late as 2000! Soon after Kagan highlighted the importance of research in this area. since they were monodentate and more of them coordinated to the central .b. Morever. mixing these ligands together was a very interesting method yielding high enantioselectivity. Until then. [16] pioneering structures emerged from laboratories of Pringle.130 Jiří Václavík. Petr Kačer and Libor Červený Cl Ru P Cl NH2 P PPh2 PPh2 NH2 Ru-diamine-diphosphine (R)-BINAP 5 OMe Cl PAr2 Ru PAr2 Cl H2 N N H2 Cl PAr2 Ru PAr2 Cl H2 N OMe N H2 Ar = 3. establishing a whole new family of chiral auxiliaries whose chirality rests on the phosphorus atom rather than the ligand backbone. [15c] who introduced monophosphonites.5-Me2C6H3: 6c [RuCl2{(R)-XylBINAP}{(R)-DAIPEN}] Ar = 4-Me-C6H4: 6d [RuCl2{(R)-TolBINAP}{(R)-DAIPEN}] Figure 2. [15a] Reetz [15b] and Feringa. [18] to implement a high-throughput experimental route for finding the right catalyst. [17] This feature enabled de Vries et al. Noyori’s original BINAP ligand and Ru-BINAP/diamine complexes. Ph.5-Me2C6H3: 6a [RuCl2{(R)-XylBINAP}{(R. cyclohexyl JosiPhos 9 BPE 7 DuPhos 8 Figure 3. Although Knowles’ CAMP has already been discussed as an efficient monophosphine. monophosphites and monophosphoramidites.R)-DPEN}] Ar = 4-Me-C6H4: 6b [RuCl2{(R)-TolBINAP}{(R. it was believed that chelating ligands were needed to obtain asymmetric induction. R P R P R R R P R P R R Fe PR2 PPh2 R = i-Bu.c). Additionally. ATH. as in the case of Me-SIPHOS 11 developed by Zhou [20] (2002). utilizing organic compounds (IPA. Noyori et al. Non-BINOL monodentate phosphorus ligands. [23] disclosed the pilot catalytic system RuCl(η6arene)(arenesulfonyl-diamine) 14 which initiated the development of asymmetric transfer hydrogenation (ATH) as a remarkable branch in chiral synthesis. Although many monodentate ligands were BINOL-based. . HCOOH/TEA azeotrope) as the source of hydrogen. so-called homocombinations occured when only one ligand was used. which was a very powerful tool for α-aryl enamide asymmetric reduction. Helmchen [21] introduced in 2002 a bulky phosphane derivative 12 capable of highly selective itaconates hydrogenation. The structure of diazaphospholidines 13 [22] manifested a great deal of creativity. regardless of the fact that this ligand was not originally intended for hydrogenation reactions.Rational Design of Chiral Ruthenium Complexes … 131 atom at the same moment. Typically. we have only described catalysts used for standard asymmetric hydrogenation (AH) where gaseous H2 was used as the reducing agent. [19] O P O R O P O OR O P O N R R' monophosphonites 10a monophosphites 10b monophosphoramidites 10c Figure 4. a recent derivative (discussed below) performed extremely well in an acrylate reduction. BINOL-derived monodentate phosphorus ligands. some noteworthy alternatives were available (Figure 5). O O P N O P H Ph N P OR N MeSIPHOS 11 12 13 Figure 5. Ligands Used in Asymmetric Transfer Hydrogenation In 1995. however one-pot usage of two different ligands (not necessarily 1:1) led to selectivity-enhancing heterocombinations. was yet one step closer to enzymes which naturally utilize designated hydrogenation media such as NAD(P)H or FADH2. Up to now. the η6-arene is represented by benzene or its derivatives. aforementioned ligands have been modified extensively by means of rational design. R2 = Bn NH R1 R2 OH 17a: R1 = Me. [28] However. R2 = H 16b: R1 = Me. this approach has remained a popular and promising way for a ligand enhancement. Many of them have been tested. employing an aromatic ligand and a chelate auxiliary (Figure 6). 2. The original catalysts were primarily Ru or Rh half-sandwich species. Since the reader at this point should have at least a basic knowledge of how such structures could be approached. relevant alterable parameters are described and real examples provided. RATIONAL DESIGN OF CHIRAL LIGANDS Since their discovery.4. the following text proceeds to the chiral ligand rational design. mesitylene R: tolyl. N. It should by now be obvious that the pool of fundamental structures. An example of an aliphatic ketone ATH is presented further in the text.2-diphenylethylenediamines [25] (included in 14) to various diaminoindanes 15. R2 = Bn 16d: R1 = Me.e. Ru half-sandwich complexes and examples of their auxiliary chiral ligands. (see Figure 7). R2 = Me 17c: R1 = Ph. Although these parameters influence one another to a certain extent. [26] β-amino alcohols 16 [27] or 2-azanorbornyl alcohols 17. In the case of Ru. R2 = Me 16c: R1 = Me. [24] The number of options started to grow intensely with the evaluation of all utilizable chiral auxiliaries. i. The systematic approach attempts to categorize (and individually quantify) all possible changes that can be made to the original structures. p-cymene. The authors were of the opinion it was beneficial to the readers to provide a concise historical review of the evolution of ligands capable of asymmetric reactions catalysis. In the next section. from the original N-sulfonylated 1. especially when followed by proper analytical methods. 1-naphthyl. Commonly adverted sites have been the steric surroundings of the donor atoms (usually P.132 Ar Jiří Václavík. . serving nowadays as a “brainstorm source”. the backbone profile. R2 = Ph Figure 6. R2 = H 17d: R1 = H.6-(CH3)3-C6H2 NH2 NHTs NH2 NHTs Cl H N H Ru N SO2R Ph Ph 15 NHTs NH2 NH2 NHTs R2 R1 NH OH 16a: R1 = Me. all of these performed well only in the ATH of aromatic ketones. R2 = H 17b: R1 = H. Petr Kačer and Libor Červený 14 Ar: benzene. causing an obstacle to a systematic assay. the angle formed by the donor atoms and the central atom etc. is truly voluminous. R2 = CH2(C6H4)C6H5 16e: R1 = Ph. O). a few examples of backbone substitution are presented. 2) substitutions at the ligating sites. thus shaping the active site cavity for the substrate. Interestingly. The main features of a ligand: backbone. The substitution may also evoke a transfer of electron density which is further discussed in a separate section. Reetz and co-workers introduced a number of different substituents into the position 3. increasing the number of P atoms in the molecule from one to three. the additional aromatic rings hindered the phenyl groups on phosphorus atoms (in Figure 8 displayed with arrows). donor atoms (labelled D) and their substituents (R). Below. favouring the transition state leading to the desired enantiomer. which made the ligand less flexible. Monodentate ligands derived from a BINOL skelet (Figure 9) have also been subject to research in this category. BINAPO. but not to 3'. and 4) major adjustments affecting the angle between the ligand atoms and the metal. A superb example of this is the improvement of BINAPO 18 by introducing ortho. a rather ineffective ligand compared with others of its kin. . changing its symmetry from C2 to C1 and adding a second stereogenic centre onto the phosphorus atom. ortho.Rational Design of Chiral Ruthenium Complexes … 133 Figure 7. Protruding substituents are able to retain the substrate molecule in a specific position. Zhang [32] inserted phosphine substituents into both 3 and 3' positions. 3) changes contributing to the firmness of the scaffold. or mixed diastereomerically. with the third phosphorus atom left unbound. Molecular modelling revealed [30] that most probably.aryl substituents to produce o-BINAPO 19 [29] (see Figure 8). It should be noted that these phosphinephosphoramidite ligands 21 are bidentate.b. 1) Substitutions on the Backbone The main backbone framework can be extended in specific directions.substitution has been examined in two different versions. [31] By contrast. novel diastereomeric ligands 20a. In the following section. giving excellent ee values whether pure. was thus improved to the much more effective o-BINAPO. The ligand’s steric and electronic properties can be modified in several ways: 1) the backbone. This way. but not affecting the donor atoms’ positioning. this is discussed in detail.c were identified. [33] came up with an inventive idea introducing a ferrocenylphosphine group. Phosphorus monodentate ligands 10 can bear a variety of R. Several examples are discussed below to point out the diversity of donor atom substitutions. Bz 20b Me O P N OR R = Me. SPh. Originally. thus giving birth to highly versatile phosphine-phosphinites and phosphine-phosphoramidites 22. Moreover. OR O P O N Me O R = Me. to hold the substrate molecule in the optimal position enabling the desired enantioface differentiation. 22a exhibited the advantage of improved air and water stability over the original phosphinite . Ph etc. this is further analysed in a separate section. The laboratories of Chan et al. Bn.substituted BINOL ligands. the residues may be electron-donating or electronwithdrawing. These ligands performed outstandingly in reducing α-dehydroamino acid derivatives (ees up to >99). SiMe3.e. Si(Ph)3 Figure 9. Ortho. Et R 20c R = Me. which naturally affects the electronic properties of the ligand. Bn. these were relatively simple as Me. Bz 20a R O P O N Me Me PPh2 O P O PPh2 21 N R R = Me. i.5-Me2C6H3: Xylyl-o-BINAPO Figure 8. Petr Kačer and Libor Červený R Ph O PPh2 O PPh2 O P Ph O P Ph Ph R BINAPO 18 o-BINAPO 19 R = Me: Me-o-BINAPO R = Ph: Ph-o-BINAPO R = 3.134 Jiří Václavík.groups at the donor site. However. i-Pr. BINAPO and o-BINAPO. Gradually. Ph. 2) Substitutions on the Donor Atoms The steric effect of the donor atom substituents is basically similar to the backbone substitution. more special alternatives have emerged (Figure 10). Et. who successfully applied carbohydrate substitution to the monophosphite backbone. a noteworthy adamantane-1-ol derivative 24 proved to be a highly selective ligand in methyl 2-acetamidoacrylate Rh-catalysed hydrogenation. cyclic enamides and enol acetates. Comparing these two structures (Figure 3). [37] From these multipurpose ligands. 3) Changes Towards Rigidity BPE 7 and DuPhos 8 represent perfect examples of a backbone structural modification leading to a similar. Ph O P O X Me PPh2 Fe Ph 22a X = -N(Me)22b X = O O O OR O O O O O P ManniPhos 23 Ph N P O N 24 Figure 10. [39] where BINAPINE 29 [40] belongs to the most remarkable ones. demonstrating that adamantane also possessed qualities of a valuable structural component in modular ligand design. [13] most probably thanks to the enhanced rigidity of the backbone. one would draw the conclusion that BPE is rather flexible within the ethylene region. to the development of a phosphabicyclic ligand PennPhos 25. . a curious reader may find more in the relevant literature. Innovative donor atom substitutions on monodentate phosphorus ligands.Rational Design of Chiral Ruthenium Complexes … 135 which allowed much a more comfortable usage. benefiting from an inexpensive facile synthetic procedure. extremely stable diazaphospholidines were reported by Gavrilov and co-workers. [38] capable of highly selective reductions of simple ketones. [35] His D-Mannitol derivative ManniPhos 23. In general. The introduction of the ferrocenylphosphine group has also been studied by other research teams. DuPhos performs even better on the same substrate series. [34] A different approach was taken by Zheng et al. yet more sterically-constrained product. As these examples represent only a fragment of possible substitutions. whereas aromatic DuPhos is built more rigidly. Many other ligands utilizing the phosphorus chirality together with phosphacyclic structural rigidity have been introduced by this group (see Figure 11 for a few examples). structural rigidity has proven extremely good for stereoselectivity which led Zhang et al. displayed excellent enantioselectivity in reduction of various functionalized olefinic substrates. [36] Alongside the BINOL-based monodentate molecules. Although BPE shows excellent results regarding selectivity. Petr Kačer and Libor Červený Me Me P Me Me (R. These so-called reverse-tethered catalysts (30b in Figure 12) displayed a higher activity in comparison to the original non-tethered structures. which in combination with the revamped tether enables superior structural rigidity. the tether may also be directed to the other end of the diamine. their structure can be reinforced using an additional covalent bonded bridge between the η6-aromate and sulfonyl group of the chiral ligand [41] (30a in Figure 12).S)-Me-PennPhos 25 P P HH HH P t-Bu P t-Bu TangPhos 26 P t-Bu t-Bu DuanPhos 27 Me N P Me P P N Me t-Bu t-Bu Me P Me Me bis(azaphosphorinane) 28 BINAPINE 29 Figure 11. there is only one. which most probably dramatically affects the . [42] The last example to be mentioned (30c [43]) harnesses an improved tether structure containing a benzene ring.Zhang’s phosphocyclic ligands. As a result. Furthermore. SO2 Cl Ru N H N H Ph Ph 30a Figure 12. Moreover. A wide palette of enantiopure substrates was prepared using a Rh complex containing this ligand. affording distinct asymmetric induction.R. Regarding ATH ligands. thus preventing the aromatic ring from its rotation. pocket-like ligand with a fairly fixed conformation.136 Jiří Václavík. Cl H Ru N Ph 30b N Ts Ts Ph N Rh N H 30c 4) Major Changes to the Backbone Changing the “length” or conformation of the backbone leads to a different positioning of the donor atoms towards the metal centre. Tethered catalysts for ATH. where cyclohexylmethyl ketone (ee 87 %) was of a particular interest given the fact it was an aliphatic substrate.S. the ligand includes another six-membered ring connecting the donor atoms. Rev. high reputation and good agreement with factual data. Figure 13. [45] complemented the concept by introducing the so-called ligand profiles for bulky phosphines. which are the conditions where the ligands actually operate. Naturally. a. Since the angles in a crystalline substance may (and usually do) differ from those in a solution. Therefore it is not surprising that Tolman’s extensive review [44] belongs to the most cited Chem. a number of approximations exist that enjoy popularity. It needs to be said that every coordination centre has its own typical M-P bond length meaning that the application of the cone angle to complexes of other metals should be considered.b) The cone angle θ. There are two ways to obtain a cone angle value. d) Comparison of θ and βn on a chelating ligand. however. the most familiar ones are discussed in detail (i. In the next section. In the case of general unsymmetrical ligands PR1R2R3. [44] Its definition is based on a space-filling model of a Ni-PR3 complex. However. c) The bite angle βn.e.Rational Design of Chiral Ruthenium Complexes … 137 complex properties. however. the cone angle is still being used very often for its simplicity. From an X-ray analysis. Ferguson et al. three semicone angle values (θi/2) were separately measured.28 Å. allowing another useful measure of the ligand shape all the way round. The Cone Angle The cone angle (Figure 13a). a solid crystalline sample is required. each of them has its own optimal area of usage based on the models they are based on. averaged and doubled. which afforded the θ as well (Figure 13b). was first implemented by Tolman. [46] one can deduct the value with reasonable accuracy. There is no universal and exact way of measuring the steric qualities of a ligand. a computational . the cone angle and the natural bite angle) and other reported steric descriptors briefly described. where the Ni-P distance is fixed at 2. articles. mostly suitable for axially symmetric monodentate phosphines. which are more likely to exist in a solution. the only difference between each being the backbone length – the longer the chain. this concept does not depend on the selection of the transition metal. [53] This was due to the four. Figure 15 depicts MiniPHOS 33. respectively). although exceptions to this exist. discovering direct correlation between the bridge length and the ligand natural bite angle. [37] The Bite Angle The cone angle may be used for the evaluation of chelating ligands. MeO MeO PPh2 PPh2 O ( H 2C ) n O PPh2 PPh2 (R)-MeO-BIPHEP 31 (R)-TunePhos 32 Figure 14. the ligand backbone rigidity should not be omitted when experimenting with the bite angle. An important feature is that adjusting the bite angle. Petr Kačer and Libor Červený approach is often preferred as a convenient method for finding conformations representing the true energy minima. However. Bidentate ligands are seldom round shaped and thus the cone angle is often not a precise measure. Nevertheless. [48] Therefore.c). as illustrated in Figure 14.9 % ee. [49] It has become a very important parameter of the backbone steric properties and several real applications are presented below to highlight its significance. TunePhos bite angle variability. [51] Bis-P* 34 [52] and substituted 1. the more active the catalyst obtained for dehydroamino acids reduction.3-bis(phosphino)propane 35. Stemming from MeO-BIPHEP 31.138 Jiří Václavík. Zhang et al. An example of this can be found in a recent paper by Gavrilov et al. The atropisomeric structure of BINAP. Original MeO-BIPHEP.0 and 99.or five. as demonstrated in the following example. [54] . one may observe significant differences both in activity and selectivity of the catalyst. Hence. ligand 35 displayed very poor selectivity (14 % ee) in contrast to 33 and 34 which both showed outstanding results (99. BINAPO. the aforementioned bonus in the form of the ligand fixation is necessary to achieve the selectivity. [47] although a different approach is preferred since the sterical description of phosphorus chelating ligands by the cone angle is not often very conclusive. TunePhos and others provided the necessary stabilization of the sixmembered ring formed upon complexation. appended an alkanediyl bridge to this structure (C1 to C6 long). It has been demonstrated that every substrate favours different bite angle range. [39] Another clear and convenient way of ligand optimization was thus invented. TunePhos 32 [50] is a textbook example of adjusting the bite angle (and smart ligand fixation as a bonus).membered constrained chelate cycles these ligands formed with the metal. Its definition is as follows: The natural bite angle is the preferred chelation angle determined only by ligand backbone constraints and not by metal valence angles. This is the reason why the natural bite angle is preferred (βn in Figure 13b. Other Steric Descriptors In some cases. at the end of the electronic parameters subsection. could be observed in the structure of a monodentate ligand 36 derived from H8-BINOL. H8-BINOL ligands. is mentioned further in the text.Rational Design of Chiral Ruthenium Complexes … t-Bu P Me P Me t-Bu t-Bu P Me P Me t-Bu t-Bu P Me 35 139 P Me t-Bu (R. White simultaneously proposed a radial profile [57b] as a plot of dependence of Ω on the P-M distance. The Rh-H8-MonoPhos catalyst offered excellent selectivity in asymmetric enamide reduction. In addition to the aforementioned ligand profile. MiniPHOS. Perpendicular (θ||) and parallel (θ⊥) pocket angles were established so as to completely describe the non-conical bidentate ligand. as the method is mainly oriented towards the electronic properties and this steric parameter followed as a consequence. A major change to the backbone moiety. The metal is considered a light source and the solid angle is then calculated from the shadow area cast upon the sphere. Koide et al.S)-BisP* 34 Figure 15. in particular the MESPsteric parameter. R' = H or Me R + R' = -(CH2)4- H8-BINOL 36 Figure 16. This method similarly utilizes CPK models obtained from crystallographic data. One theoretical approach. Radial profiles comparison has enabled further analysis of the ligand steric requirements. i.e. White and co-workers introduced an interesting solid angle (Ω) concept [57] which is based on projecting the ligand atoms on the inside of a unit sphere as depicted in Figure 17. mostly 3% higher than in the case of original MonoPhos (i.R)-MiniPhos 33 (S. For this reason. Bis-P* and bis(phosphino)propane structures. as displayed in Figure 16. although not affecting the bite angle. 10c possessing the NMe2 heelpiece). regardless of their special burden related to their empiric dependency. defined the pocket angle [56] for chelating phosphorus ligands as an alternative to the cone angle used preferentially for monodentate ligands. further descriptors are provided in the following text. A recent paper by Guzei [57c] represents a good complement to this topic with some improvements included. . the above descriptors are less suitable for characterizing the ligand steric requirements. [55] O P O N R R' R = R' = Me or Et R = -CH(Me)Ph.e. co omputational attempts a have e also been re eported on bo oth full DFT T and ONIOM M [60] – de esignated DFT T-S4' and ON NIOM-S4'. S4' can be worked ou ut easily as a difference bet tween ∑(<M-P-X) and ∑(< <X-P-X). Under rstandably. . Figure 18 displays d an alt ternative to the e cone angle established e by Harvey and co-workers c .383 Å) exceeds the sum s of van de er Waals radii i of the two ato oms (3. The par rentheses repres sent a general sp pacer or the pr resence of two monodentate m lig gands. Fi igure 18. [59] For the mode el complex M-PXn. the S4' steric parameter wa as first introd duced by Orpe en [58] and us sed as a descr riptor by Cund dari et al. a planar p He8 cyc cle of a constra ained radius (2. start ting with a pre e-optimised fr ree ligand geo ometry. The li igand projection n used for solid angle (Ω) calcu ulation. Also known as the He8_ring. w which makes it very user-fr riendly. Recently quite q popular. They introduce ed the He8_ste eric parameter r [61] which simulates s spac cial interaction ns between th he monodenta ate ligand in question q and other o ligands in cis configu uration in an octahedral co omplex. The in nteraction energy (which is s in fact repres sented by the He H 8_steric des scriptor) between the ligand d and the He8 auxiliary a is al lmost exclusiv vely of a steri ic origin as th he He-P distan nce (3.2 Å). Harve ey’s He8_ring (a a) and He8_wed dge (b).14 40 Jiří Václavík. Petr r Kačer and Libor L Červený Fi igure 17. the S4'' parameter ca an be obtained d directly from m crystallograp phic data using only the cor rresponding bo ond angles. ac ccordingly (co omputational methods m are di iscussed furth her in general). which w is the re eason why ele ectronic contributions are .28 Å and the whol le structure op ptimised.5 ( Å) was pl laced opposite e the phospho orus atom at a fixed distanc ce of 2. Ther refore. large biomolecules.. the system investigated and the accuracy aspired. has been soon afterwards developed for P. However. [62] In this situation. The practical usage of these parameters is further discussed in this text. owing to technological advances in computing centres. every second atom of the eight-membered ring) in the ligating sites of an octahedral complex in a fixed 2. In his landmark work. semi-empirical or DFT levels of theory. it turned out to be more convenient to fix four He atoms (strictly speaking. causing electronic enrichment of the metal and subsequent transfer of electron density into the CO sσ* antibonding orbital.00 Å where possible. [44] Tolman investigated a large series of PR3 ligands incorporated in a [Ni(CO)3PR3] model complex and ranked them according to νCO(A1) in CH2Cl2 solution. MNDO) and MM (MM2) was presented by Chin et al. Electronic Ligand Descriptors Having described the steric parameters of ligands. Computational Methods Before the electronic descriptors are presented. In a chronological sequence.28 and 2. defining the Tolman’s electronic parameter (TEP) scale. still have to settle for molecular mechanics or molecular dynamics. Theoretical chemistry offers a variety of tools that may be utilized to obtain the descriptor values and thus molecular modelling of such systems can be carried out using molecular mechanics. it is necessary to give an account of descriptors concerning their electronic properties. the metal was deleted and the resulting structure optimized. Nowadays. followed by certain advanced successors. The angles between He atoms were constrained at 90°/180° values and the starting ligand geometry was adapted from a tetrahedral zinc complex. [65] however these model phosphines were not actually real ligands used in asymmetric synthesis. Since these can actually be applied to all structural changes. most of the ligands can be computed on the semi-empirical or even DFT level. N-M (2. or the shortest possible distances for ligands where this could not be accomplished). [64] An illustrative comparison of QM (MINDO/3.N bidentate ligands. Electron-donating R groups increase the phosphine basicity. After setting the donor-metal distances P-M. a general outline of computational approaches is provided. there are several pioneering concepts among the electronic ones. Pure ab initio computing comes into question merely in the case of the simplest phosphines due to its enormous hardware requirements and employing DFT counts with reasonably small molecules and a well selected basis set. A direct correlation was shown between the stretching frequency νCO(A1) and electronic properties of the phosphine ligand. representing another quickly evolving field of rational design.Rational Design of Chiral Ruthenium Complexes … 141 almost negligible. one probably chooses the level of theory according to their computational resources. Parallel to steric descriptors. while the account of the sterical descriptors was given more conveniently together with the backbone adjustments. this weakens the CO bond and its stretching frequency decreases. [63] Consequently.28Å distance from the transition metal. A similar concept. Naturally. On the TEP . the descriptors based on experimental work are first demonstrated. it has been described at the end of this subsection. called He8_wedge. while the section is concluded with an overview of computationally accessible parameters. so Crabtree employed a cis-[Mo(CO)4L-L] complex to measure νCO(A1) and designed a formula which enabled a conversion of these values onto the original Ni-complex based TEP scale. 1JPPt. Firstly. Therefore.g. [73. Indeed. Afterwards. while these methods afforded only indirect results via a certain complex. Petr Kačer and Libor Červený scale. whose notation stemmed from its original purpose of an aryl effect description. [67] The Lever electronic parameter (LEP) [68] is a useful alternative to those experimentally obtained by IR spectroscopy. Similarly to TEP. which can be chosen according to the ligand requirements. the most basic phosphine P(t-Bu)3 was selected as a reference ligand in the Ni complex (with the A1 band of 2056.1 cm-1) and other phosphines were related to [Ni(CO)3P(t-Bu)3] through the parameter χ. Giering and co-workers proposed an appreciable concept. by Allman and Goel. Lever defined the LEP parameter as 1/6 of ERu(III)/Ru(II) potential for RuL6 in acetonitrile. Secondly. however an interconversion is possible between these scales.142 Jiří Václavík. showing a fine correlation with the electronic data. σ-donor and σ-donor/π-acceptor according to correlation of EL°' of Mn and Fe complexes with pKa values of the phosphines in question. Considering Mn/Mn–1 redox potentials to be fully additive. every complex may possess its own ν scale. his extensive list of LEP values for over 200 ligands has also been used as a benchmark for validating theoretical methods. they came up with a sophisticated quantitative analysis of ligand effects (QALE). any carbonyl-containing complex may be used in the TEP scale. coupling constants (1JPB. the 1JPC constants did not seem to be linked to the phosphorus basicity at all. πp (characterizing π acidity) and Ear. The next focus is on theoretical investigative methods which are invaluable in the field of ligand design due to the experimental unavailability of required data and an appealing possibility to predict ligand properties. [69] However. electronic properties of the ligand were our target. revealing the complexity of this problem. [71] where the phosphines were distributed into three classes: σ-donor/π-donor. These parameters were χd (representing σ donor ability). accordingly). as a matter of fact. 1JPW) were studied as well. [67] Regarding the basicity.74] Among alternative experimental ways of investigating the phosphine basicity is the usage of 13C NMR spectroscopy. and the π-backdonation from the metal to an empty orbital of the phosphorus atom (arguably σ* [70]). although its role is now considered operative even in non-aryl substituted phosphines. 1JPSe. Tolman’s system was insufficient for complexes with two cis-configured phosphine ligands/a chelating ligand. [72] stepwise establishing three parameters describing the electronic properties of phosphines. Crabtree [66] generalized this approach and showed that. Since DFT frequency jobs investigating bulkier phosphines tended to be . one would have obviously expected some kind of experimental pKa or pKb studies. While these coupling constants were found to be related to the corresponding bond strength (and to P basicity. Crabtree reported the computed electronic parameter (CEP) [73] using frequency calculations on a DFT level of theory. As an analogue to TEP. pKa values of conjugated acids to a series of PR3 tertiary substituted phosphines were measured e. Taking advantage of those central atoms which are also NMR active nuclei. these experimental models exhibited one or more major drawbacks which provoked others to come up with improved solutions. the overall electronic effects of the ligand (described by Tolman’s electronic parameters) were a sum of two opposite phenomena – the σ-donation of the phosphorus lone pair into the metal’s vacant orbitals. Chemical shifts of carbons from CO ligands in various complexes were found to be affected by the presence of other donor ligands. Considerable efforts have been made to isolate these two factors. eliminating any influences of a complex species. i. pKa of PR3 conjugate acids.e. The key idea was finding the global minimum Vmin of MESP pertaining to the lone pair region of the phosphine ligand. Describing the relative positioning of the molecules (i. more advanced methods were developed. enabling the steric effect of the phosphine substitution to be observed. It was the bare ligands that were evaluated. Having had a good agreement with TEP. albeit in a very brief form. P(t-Bu)3 showed the highest “σ-donating power” by having the lowest Vmin value. In this configuration. Profuse works have been dedicated to this field in order to understand the reaction mechanisms.e. their semi-empirical parameter SEP turned out to be a highly suitable computational option for quick in silico testing. presented a handy example relevant to this topic. In 2006. if electron donating groups were present. Vmin value decreased and vice versa. a noticeable attempt was made by Suresh [76] to separate electronic and steric properties. The MESP approach did not require any experimental background and therefore could also be used to predict the properties of new structures in silico. substrate and catalyst) during TSs explains its relation to the reaction’s enantioselectivity. the number of ligand steric and electronic descriptors is significant and only a limited selection is presented here. the positioning of the link hydrogen atoms of PH3 depended on the steric requirements of the neighbouring R groups. DFT analysis of transition states (TS) is discussed as well as some computationally cheaper approaches which may partially or completely avoid costly QM calculations. and a rationale of the origin of enantioselectivity is included. When a prochiral substrate is present in the chiral environment of the catalyst. The findings of Suresh and Koga. Evidently. The investigation of the full catalytic cycles is not covered within this text given the complexity of the problem. while the R groups were treated with molecular mechanics. which was exactly the area of interest as the lone pair electron density was connected to the phosphine basicity. the results fairly correlated with Tolman’s νCO(A1) scale. PH3 was included as well to set up a reference point of unsubstituted phosphine. the interested reader is encouraged to study cited literature for more ligand descriptors. Cundari and co-workers [74] devised a semi-empirical quantum mechanical approach allowing a wide range of feasible calculations. Having followed these simple analogues to the original works of Tolman. certain options for its approach to the . ONIOM method was used to achieve this: the surroundings of phosphorus atom (in each case bearing the hydrogen atoms. a computational method consistently describing electronic properties of substituted phosphines (PR3). yielding an invaluable expertise in the form of highly detailed information on the very nature of the catalytic process. This “tampering” with the phosphine bond angles affected the p-character of the lone pair. For this reason.e. i. [77] Reaction Mechanism Analysis This chapter would not be complete without an account of the mechanistic aspects of asymmetric catalysis. LEP and CEP.Rational Design of Chiral Ruthenium Complexes … 143 computationally very demanding. In the following text. Moreover. ∆E of a complex formation reaction and finally ∆H° and E° for an iron complex redox reaction (FeII/FeI). Similarly to Tolman’s ranking. [75] who have established the convenient molecular electrostatic potential (MESP). PH3) were calculated using a DFT level of theory. the computational analyses of the transition states (TSs) are described. again using the MESP computational concept. proposing sagacious routes for ligand computational screening by employing state-of-the-art research technology. The active catalytic site is thus modelled by QM methods due to higher accuracy requirements. [79] In other words. In such a case. better methods. they will certainly facilitate the development of subtle techniques useful in ligand design. For larger molecules.81] If only a few TSs are likely to form for structural reasons. developed by Norrby. these can really be obtained by investigating a rather small catalytic system. [80] As the quadrant approach has already been well described. . while in others it proceeds with high activity and/or selectivity. [53. alternative procedures need to be employed. are designed advantageously to fully occupy three quadrants. relevant literature is cited. which can be accomplished with ordinary MM methods. as long as the molecules are not too big. TSs may be explored computationally in detail thanks to their limited number. it would be possible to predict catalyst properties for a certain stereoselective reaction entirely in silico. [82] dividing the entire system into sub-areas treated by different tools. Some catalysts. so as to disallow formation of TSs within these regions. The process of the substrate approaching the catalyst can be modelled as well. especially regarding electronic properties. The quadrant approach has been the most utilized one for TSs analyses. while the surroundings are treated by MM. like MP2. like 14. CONTEMPORARY TRENDS IN CATALYST DESIGN In an ideal world. Although such a quantum-mechanical approach yields very precise outcomes with respect to geometries. Such an analysis may provide us with useful reasoning as to why the reaction does not take place through a TS within a certain quadrant. [84] revealing the differences between the four quadrants. Although these “prototypes” have not yet been implemented into a routine use. Every route is then followed by a more or less probable diastereomeric TS. promising attempts have recently been emerging. should be used for energy calculations. thorough computational analysis on a DFT level is feasible on contemporary resources. The QM/MM method is the most popular way of reducing the computational resource needs. Petr Kačer and Libor Červený complex are more sterically and electrostatically [78] favoured than others.g. The energy difference between the favourable and disfavourable TSs determines the reaction ee and is temperature dependent. The successful ligands used in AH and ATH are chiral rigid molecules which strive for the reaction to proceed preferentially via the favourable TSs leading to the desired enantiomer. BINAP with 68 possible TSs. like e.144 Jiří Václavík. The space surrounding the catalyst is divided into four equal quadrants and the entire problem is thus more systematic. [83] allows TSs analyses merely on a MM level. This method is called QM-guided MM (Q2MM) and employs custom force fields derived from previous QM calculations. An important feature of Q2MM is that these modified force fields actually allow the TSs to be calculated as energy minima. raising the temperature leads to a stereoselectivity decrease. which afford results good enough since these parts of the system are mostly sterically governed and their description by a force field is sufficient. However. Another possibility. Even though the reality is still far from this prospect. others are much more complicated. Despite the extreme usefulness of such accurate results. They identified a gap in the map pertaining to the phosphines with very low basicity. A series of 61 representative ligands was used. Since experimental parameters were not uniformly accessible. θ and showed characteristic areas of differently substituted ligands (e. more precise ligand space reference points could be established. In other words. P(t-C4F9)3. using both supercomputers and distributed computing Grid methods.Rational Design of Chiral Ruthenium Complexes … 145 A successful solution requires solid foundations applicable to a broad variety of situations. Already the fact that such a large-scale ligand screening combines several techniques of limited accuracy (i. Obviously. The target of this project has been an automated global ligand descriptor assemblage. able to elegantly demonstrate that 13C NMR chemical shifts were mainly related to the electronic properties. asymmetric (PA2B) and several utterly exotic molecules. Their conclusion was that alkyl and aryl phosphines were surprisingly similar in terms of both steric and electronic properties. Ligand Knowledge Base In 2006. each of their own). An emphasis was put on careful selection of enough reliable descriptors and proper statistical evaluation methods in order to create a consistent infobase applicable to a variety of molecules. with the aim of including a wide range of compounds. This was already broached by Tolman [44] who plotted νCO vs. functionally similar ligands should reside. the computational level of theory) implies that the entire process is rather delicate and every component should be wellconsidered to reach the required robustness. Tolman was e. low sensitivity or difficult in silico automatization. which has already been outlined. Cundari and co-workers [59] developed Tolman’s primary ideas and presented stereoelectronic phosphine maps based on MM/semi-empirical calculations. and obtained a 3D landscape revealing the ratio of θ and νCO effect on Z in a slope-shaped manner. Consequently. predicting the properties of unknown species. showing the feasibility of the whole .g.g.e. the group of Professor Harvey [61] came up with a set of computational descriptors of monodentate phosphorus ligands which they called the ligand knowledge base (LKB). more importantly. we give an account of the most recent attempts. Then he added a third parameter (generally denoted Z). Although Tolman used corporeal models to manually 3D-plot his results. The idea of a ligand map has been brought into play.g. including symmetric (PA3). Harvey’s group chose to exploit crystallographic databases by means of molecular modelling on DFT level of theory. Here. a comparison of these with theoretical descriptors was made possible. with a reliable set of descriptors and solid framework. This way. this is mostly conditional on a proper application of the knowledge obtained by investigating the ligand steric and electronic descriptors. choice of descriptors. as in the case of e. showing that within a certain region of the map. capable of interpreting experimental data and. some descriptors needed to be excluded due to their excessive specificity. but at the same time a sufficient number of them had to be utilized to record all important features of the ligands. he showed an invaluable way of ligand mapping. whereas ΔH for reactions of excess phosphorus ligands with a certain Pt complex proved to be sterically-governed. Given the availability of a wide range of empirical data for monodentate phosphines. and pointed out the unusual qualities of cyclic phosphines which expanded the map to a considerable extent. which would depend both on θ and νCO. P(OR)3 and aliphatic PR3 only occurred in certain areas. enabling efficient catalysts identification.).000 species per hour. proton affinities.86] showed that in silico screening of even highly extensive libraries could be accomplished without any MM or QM calculations or three-dimensional models.N. Spaces B and C shared a connection through . while 2D descriptors were able to analyze ca. The ligands were also investigated in both free and in protonated and borane adduct forms. over 105). Later. Their Pd complexes were also utilized to obtain information on their electronic properties. continuous space C was defined to comprise figures of merit (TOF. Space A was inherently connected to continuous space B. the first chelating ligand map was proposed. Some utilized descriptors were also contextualized with similar but more often used ones to justify their applicability (for example. ee. their most significant contribution was the development of a complex system for the construction and refinement of virtual catalyst libraries. PC2 plots. Harvey et al. the qualitative information obtained by this method became quite useful. while each dimension in A pertained to a different building block (ligating.and P. etc. Petr Kačer and Libor Červený concept. which they called LKB-PP. B. adduct binding energies. Chemically similar ligands tended to cluster in certain regions of the PC1 vs.e. This way. backbone and residue blocks). [62] They used a similar selection of descriptors but applied some bidentate-related ones as the ligand bite angle or He8_wedge. the usage of linear regression for predictive purposes turned out to be limited due to scarcity of appropriate experimental data. 100. Nevertheless. which actually was not used for LKB at all). As they pointed out. composed of catalyst descriptors and reaction conditions. NBO charges. Multiple linear regression (MLR) was also utilized to confirm the correlation between empiric data and calculated descriptors. the simplification in the form of 2D topological descriptors did not offer very accurate results but was sufficient enough for a preliminary exploration of large ligand sets (i. TON. Three Spaces Inspired by quantitative structure-activity and structure-property techniques (QSAR. He8_steric was contextualized with Tolman’s θ. Although the quantitative interpretation of these maps did not prove reliable owing to PCA sensitivity to outlier values. and several steric parameters (He8_steric and S4' [58]). This way.ligands. which represented a next step after Tolman’s pioneering ligand map. [86] even the MM level 3D calculations handled only around 100 ligands per hour. In the end.146 Jiří Václavík. C were established. [87. As the number of often substantially correlated descriptors was quite high.88] They specified their search to an organometallic catalyst utilising bidentate ligand.P. Discrete space A comprised all catalyst structures to be explored. each point in the space uniquely determined a different structure. thus enabling prediction of experimental parameters for unknown ligands investigated computationally. which was disassembled to the very basic building units. Of course. QSPR) commonly used for drug discovery in the pharmaceutical industry. geometry descriptors indicating the differences after complexation. reported a similar concept applicable for chelating P. Consecutively. Rothenberg et al. the so-called principle components (PCs) were derived from the descriptors as their linear combinations. In comparison to the original monophosphine configuration. potentially useful areas of the ligand space could be quickly discovered and further explored by more accurate methods to actually identify (or predict) the most satisfactory molecules. three multi-dimensional spaces A. the following decriptors were used: HOMO and LUMO energies. Finally. [85.. These descriptors were presented and discussed in terms of their efficacy. [89] opened another innovative way of computational searching for the best catalysts using simulated evolution. practical experiments still play the decisive role. the genuine in silico catalyst design still remains a great challenge. only the basic idea of the whole process could be presented. Nonetheless. a robust set of yardsticks is critical to properly describe the ligands and complexes. The toolbox for asymmetric synthesis has developed extremely within the past four decades and is still a key area of contemporary research in this field. Simulated Evolution Very recently. the goal of this method is to find the majority of good catalysts in a few generations. Subsequently. CONCLUSION This chapter has attempted to present a concise insight into the contemporary methods of catalyst design applicable not only to Ru complexes used in asymmetric hydrogenation but also to various other catalytic systems. a library of Noyori-type ATH catalysts was assembled and evaluated by means of HTE. Regardless of the vast availability of the tools exploiting theoretical chemistry. In order to be able to effectively master the extensive catalyst/ligand libraries and discover new species by reliable predictive models. some of the best catalysts were reached evolutionarily. and utilizing a custom-programmed genetic algorithm. Obviously. reliability and applicability for in silico compound searching. the simulated evolution might be another promising way of chiral catalyst design. one could observe the desired properties (C) related to the actual catalyst structures (A). especially if accompanied by real laboratory experiments. If developed further. This idea represents a major step forward since it has contrived to link the real catalyst performance properties to its structure. Due to an immensely rapid development in this exciting field. calling for more sophisticated methods as full scale QM calculations or reaction mechanisms analyses. At first. Riant et al. Although computational methods afford an enormous assistance. a mother generation G0 was brought together from this library either manually or randomly. Nevertheless. [90] Correct statistical data interpretation and thorough validation of the computing models are vital for the models to be both employable and trusted. even when using only 10 % of the library for G0 creation. one should be vigilant in using these methods because. a cursory computational search may often prove insufficient and fallible. . Developing and improving such a model is both intriguing and desirable as it can be a very powerful means of catalyst rational design.Rational Design of Chiral Ruthenium Complexes … 147 QSAR/QSPR modelling methods and this way. citing the relevant literature for further details. as was succinctly pinpointed by Rothenberg: “Just because a program did not crash does not mean that the results are meaningful”. 2'. LIST OF ABBREVIATIONS asymmetric hydrogenation asymmetric transfer hydrogenation 2.1-di(4-anisyl)-2-isopropylethylenediamine DFT: density functional theory DIOP: 2.6.3.2-bis(alkyl-methylphosphino) ethanes BPE: 1.5'-tetrahydro-3.2'-diol H8-BINOL: HOMO: highest occupied molecular orbital HTE: high-throughput experimentation IPA: isopropyl alcohol JosiPhos: (R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyldicyclohexylphosphine L-DOPA: levodopa.3'-tetrahydro-1H.1-bis (alkylmethylphosphino) methanes MLR: multiple linear regression MM: molecular mechanics AH: ATH: BINAP: BINAPINE: .3-O-isopropylidene-2.1’-binaphthyl 4.S)-1.6'.3-dihydroxy-1.R)-1.148 Jiří Václavík.4'.6'-dimethoxy-1.1')biisophosphindolyl DuPHOS: 1.2-bis[(o-anisyl)-(phenyl)phosphino]ethane DPEN: 1.3'-bi-3H-dinaphtho[2.1'H-(1.4-bis(diphenylphosphino)butane DIPAMP: 1.2-bis(phospholano)benzene ee: enantiomeric excess 5.7'-diyl]phosphoramidite MESP: molecular electrostatic potential MINDO: modified intermediate neglect of differential overlap MiniPhos: (R. L-3.7.2'-bis(phosphino)-6.1'-spirobiindane-7.1'-biphenyl BisP*: (S.7'.2-bis(phospholano)ethane CAMP: o-anisylcyclohexylmethylphosphane CEP: computed electronic parameter CHIRAPHOS: bis(diphenylphosphino)butane CPK: Corey-Pauling-Koltun DAIPEN: 1.1'-binaphthyl-2. Petr Kačer and Libor Červený ACKNOWLEDGMENT The authors wish to acknowledge with gratitude the financial support by the Grant Agency of the Czech Republic (Grant GACR 104/09/1497) and the Ministry of Education of the Czech Republic (Grant CEZ: MSM 604 613 7301).4-dihydroxyphenylalanine LEP: Lever electronic parameter LKB: ligand knowledge base LUMO: lowest unoccupied molecular orbital ManniPhos: monophosphites derived from D-Mannitol Me-SIPHOS: N-Dimethyl-[1.1-c:1'.2-diphenylethylenediamine DuanPhos: 2.2'-bis(diphenylphosphino)-1.4'-di(t-butyl)-4.5'.1'-bi-2-naphthol BIPHEP: 2.2'-di(t-butyl)-2.8'-octahydro-1.5.8.2'e]phosphepin BINOL: 1. . Rev. 1977. P. 2003. Soc.. (b) Ohkuma T. Am Chem. Chem.. J. Dang T. Kagan H.. Org. J. 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Lutz F. Chem. [82] Tomasi J.. Chem. Chem. Kessler M. Rothenberg G. [78] Brandt P.. 1997.. [74] Gillespie A.. 7033-7037.. Eur. 15. 137.Rational Design of Chiral Ruthenium Complexes … [90] Rothenberg G. Catal. 2-10. 153 . Today 2008. . INTRODUCTION Precisely what is. Queen's University Belfast. the original shape is recovered [1-2]. the gelator. Various organogels and metallogels offer rich possibilities for catalysis.In: Homogeneous Catalysts Editor: Andrew C. formed by a second species. they exhibit some rheological properties like those of a solid. 2) catalysis by coordination polymer gelators. Stranmillis Road. UK. and what is not. hydrocarbon etc. Interestingly supramolecular gels show enhanced activity compared with their homogeneous analogues in a number of cases. 3) catalysis by post-modified gels. Poehler ISBN: 978-1-61122-894-6 © 2011 Nova Science Publishers. Unique new catalytic properties can arise from combining gels with catalytically active centres. There are three strategies in literature: 1) catalysis by discrete gelators. Although such gels are mainly liquid (often > 97%). water. Many. Belfast. but not all. Supramolecular gels can be used in catalysis by incorporating a catalytically active unit as part of the gelator. a gel has proved notoriously difficult to define [1-5]. They exhibit some combined advantages of homogeneous and heterogeneous catalysis. Chapter 5 SUPRAMOLECULAR GEL CATALYST: BRIDGING HOMOGENEOUS AND HETEROGENEOUS CATALYSIS Jianyong Zhanga and Stuart L. China. b) Centre for the Theory and Application of Catalysis (CenTACat). ABSTRACT Supramolecular gels have received growing attention in recent years. up to a certain limit. ethanol. for example they are elastic. Jamesb a) School of Chemistry and Chemical Engineering.) which interpenetrates with a persistent network structure. Inc. Northern Ireland BT9 5AG.g. consist of two continuous phases which interpenetrate on the macroscopic scale [1-10]. Sun Yat-Sen University. All of the examples discussed herein consist mainly of a liquid (e. meaning that after deformation. They represent a novel type of soft materials which may find application in various aspects. Guangzhou 510275. The . School of Chemistry and Chemical Engineering. David Keir Building. For example. and which are not reversible. heating can cause a change to a simple liquid phase (sol) and subsequent recooling can reform the gel. These typically do not have sharp gel points [3-5]. and tertiary structure (micro. The temperature at which the transition occurs is the gel point (Tgel). but solid-like rheology. Many supramolecular gels form reversibly. van der Waals attraction etc. within the liquid phase.156 Jianyong Zhang and Stuart L. metal coordination. this can lead to weak gels. Gels formed by changing the temperature are called thermotropic. the aggregation forms the secondary structure. However. for example. James apparent contradiction between their mainly liquid constitution. The molecular organization within the fibres of a gel may be crystalline. It is still difficult to predict whether a gel phase will form from knowledge of the molecular structures of a liquid and a potential gelator. 8].to micrometer scale). The network structures are often made up of fibres. When the connections within the network are strong (e. vesicles and so on. However. Characteristically. sheets. while in protonic environments. Alongside the general development of supramolecular chemistry. Hydrogen bonding is believed to be a common driving force for aggregation of gelators in organic solvents via forming 1D hydrogen-bonded network. which prevents the liquid constituent from flowing freely (although the molecules of the liquid continue to diffuse throughout the structure). or due to easily disrupted entanglement. The difficulty in predicting gelation is therefore related to the difficulty in predicting crystal structures. This type of supramolecular self-assembly can occur through solvophobic effects. which is considerably complicated by polymorphism or supramolecular isomerisation and relies on understanding the selection of a given supramolecular molecular packing mode [12]. and its attraction to the liquid. or LMWGs) has increased greatly in recent years. Gels with networks which are maintained by covalent bonds. Distinction is also often drawn between gels based on aqueous phases (hydrogels) [10] and those based on organic phases (organogels) [7. Alternatively. Those formed by changing the concentration of the gelator are called lyotropic. or due to strong entanglement). small molecules can also gelate by aggregating into fibres within the liquid phase [3-10]. hydrogen bonding. predominantly covalent bonds. is due to the persistent character of the network. Where network connections are weak. Both strong and weak gels can be reversible. such as fibres. this can lead to so-called strong gels. and. Other metalrelated interactions like metallophilic attraction are also important for the primary aggregation in gels.to millimeter scale) (Figure 1). The gelators themselves may be polymers. Various classifications of gels are commonly used. or inorganic particles [1-2]. The primary molecular level recognition promotes the aggregation of the gelator molecules. give rise to X-ray diffraction patterns [11]. solvophobic effects are more important to protect from solvent. Like protein. and normally does not disrupt the gel network when a gelator gelates metal-containing liquid. well defined gel points. metal coordination is expected to play a key role in metal-containing gels. Gels which have networks maintained by weaker intermolecular forces (and are normally reversible) are termed physical gels [9]. the study of such small molecule gelators (often called low molecular weight gelators. Metal coordination may be employed to form 3D matrix when a metal complex is a gelator. These propagate and interconnect. such gels exhibit sharp. a gel has a primary (angstrom to nanometer scale). micelles. secondary (nano. and finally the secondary aggregates are entangled to form the 3D tertiary structure to trap solvent [10]. or entangle.g. are often termed chemical gels. gels are potentially more complex to understand since they are . through a change in spectroscopic. urea-type groups etc.g. The primary.g.22]. especially porous materials.24] (e.14].28]). it is also worth mentioning that Shinkai proposed that 1D growth of the fibres may be correlated with the molecular packing [13. and potential applications as stimuli responsive materials [18-20]. and metal centre for metal-containing gels. template of various metal. A gel may be thought of in some ways as a failed crystal. This is achieved by polymerization. The fact that many supramelecular gels form reversibly makes them of interest as responsive materials [18. certain families of gelator molecules have emerged. In this regard. to species which ligate or interfere with ligation [25].Supramolecular Gel Catalyst 157 often based on two components and the interaction between the liquid and the gelator also needs to be understood. Figure 1. electronic or magnetic properties [27. One of the interesting aspects of gels is their ability to template other structures. and Dastidar has proved this point and show crystal engineering concept can be exploited to design simple LMWGs [1517]. However. their structural features (e. many gels are still discovered serendipitously. They have been applied in the food. Supramolecular gels have been found applications in various areas due to its unique twophase structure. nonometer-size matrix. cosmetic and petroleum industries. as will be seen below. and to a degree.) may be incorporated into the ‘design’ of new gelators with a degree of optimism and rationality. Due to the difficulty in predicting gel phases. precipitation or reduction of . biomaterials [23] and electronic devices [23] have also been reported. secondary. because propagation has occurred predominantly in only one direction (if it is based on fibres) and prevented in the remaining two. or by redox triggers [26]) and for signaling that response (e. and tertiary structure of a self-assembled supramolecular gel of a urea-based LMWG [10]. changing their physical state in response to physical or chemical triggers) and the presence of metal ions enriches the scope for responsiveness itself (e.g. inorganic and organic materials [21.g. comparison of the X-ray powder diffraction patterns given by a gelator in its crystalline form(s) with that from its gel can help to identify the gel’s molecular packing [11. whereas G'' is a measure of the energy lost as heat. Information on molecular packing modes can also be obtained from analysis of wide X-ray diffraction combined with modelling [35]. In addition. The temperature at which gelation occurs for thermotropic gels. which are formed from strong network connections. of molecular stacks within the fibres [37]. Generally for strong gels. which is then heated until.30] and NMR [31] spectroscopies can give information on the presence of hydrogen bonds. at Tgel. cryoscopic-TEM and – SEM can be applied in which the sample is prepared by rapidly freezing it to liquid nitrogen temperatures to preserve the original structure and imaging performed at low temperature. and inducing oscillatory shear in the gel by movement of one surface. Rheological study [38–40] of gels can give information on the number and strength of connections in the network. and usually provide high reaction rate and afford high selectivity and yield. infra-red [29. stacking) of aromatic groups.158 Jianyong Zhang and Stuart L. homogeneous catalysts have a number of drawbacks. With regard to the molecular packing within the gelator. To investigate the larger scale structure. James precursors in the liquid phase. Spectroscopic indications of Tgel may differ from rheological determinations since the former detects association at the molecular level whereas the latter may depend on larger scale association. For example. Alternatively. Small angle X-ray or neutron scattering can give information on the packing. electron microscopy can be applied.g. sample preparation can involve preliminary drying. However. may be measured by the so-called dropping ball technique. CHARACTERISATION TECHNIQUES Various techniques can be used to gain structural information on different length scales [10]. Due to the need for a high vacuum. By placing the gel between two surfaces.36]. To address the problems. and more generally the local environments [32] and motions [33] of functional groups. for example. heterogenising homogeneous catalysts by immobilisation is a trend toward developing efficient catalyst recycling systems. G' is a measure of how much energy is stored in a material upon deformation. Various structures including silicas. various parameters can be obtained including the complex modulus (G*). . GEL FOR CATALYSIS Traditional homogeneous catalysts have identical catalytic sites and clear structureactivity relations. G'>>G''. the ball falls through the material. and subsequent dissolution or calcination to remove the gelator network. A small ball bearing is placed on the gel. the problem of recycling of the catalyst leads to loss of expensive catalysts and to impurities in the products. the storage or elastic modulus (G') and the loss modulus or (G''). Tgel. for example [34]. The method offers extensive possibilities for controlling the morphologies of diverse materials. but this can also cause to structural changes. Absorption and emission spectroscopies can give information on the packing (e. Supramolecular Gel Catalyst 159 zeolites and organic polymers have been developed for this purpose [41-43]. Therefore. Well-defined objects (fibres) in the nanoscale. The gel network has a large surface area in contact with solution. etc. The solid-like properties of gels would result in facile isolation of the catalyst by simple filtration. Easy-to-handle. Dynamic supramolecular interactions may offer supramolecular gels some new properties different from those of traditional supported catalysts. and favours transport of large molecules to and from the active sites. drug release. Supramolecular gels have recently been used in catalysis as a new strategy to design catalyst recycling systems. Rapid progress of supramolecular gels provides a rich pool for active catalysts and allow for rational design and synthesis. Because of the reversibility of supramolecular interactions. supramolecular gels may provide a suitable model for understanding of emergence of life and construction of cell mimetics [45]. pH. stimuli responsive. pH. However. supramolecular gelation can be easily modulated by external stimuli. . as well as the special features of their supramolecular nature. the structure of the catalytic sites in supramolecular gels can be controlled at a molecular level.45]. Embedding the catalyst into a 3D gel network allows for its easy recovery after the reaction comparing with traditional homogeneous catalysts. In contrast to conventional polymersupported heterogeneous catalysts. concentration. Catalytically active centres can be incorporated into gelators directly according to their driving forces for molecular aggregation or by post-modification. light and other chemical or physical stimuli. these methods often suffer from difficulties to retain or raise the activity and selectivity. The gel has large specific surface area and the catalytically active units located in the gel fibres are accessible to solute molecules. In addition. Catalytically active motifs have been incorporated in supramolecular gels because of their following advantages as catalyst [44]: • Efficient and readily accessible. Three strategies have appeared in literature: 1) gelation by discrete organo-/metallogelators. sensing. because supramolecular gels are formed from the ordered aggregation of small molecules through non-covalent bonds to yield elongated supramolecules that further aggregate to fibres. which are different with either amorphous polymers or crystals with infinite long ranged order with periodic arrangement of asymmetric units. Supramolecular gels are characteristic of finite short ranged order with periodically disordered arrangement of the building units.. Catalytic function of gels can be expected to be controlled by stimuli such as temperature. • • • • In general supramoelcular gel materials combine some advantages of homogeneous and heterogeneous catalysis. such as temperature. resulting in their potential applications in photonic. Additionally the 3D porous structure of gels facilitates high molecular diffusivities. or catalytic materials. 3) post-modification of a preformed gel with catalytically active centre (Figure 2) [44. The gels contain wellordered arrays of catalytic or binding units or stimuli responsive subunits. 2) gelation by coordination polymer gelators. CATALYSIS BY DISCRETE GELATORS 1. whereas the conversion was not influenced (Table 2). which forms hydrogels at concentrations greater than 0. In these early reports.160 Jianyong Zhang and Stuart L. TEM revealed formation of high-aspect-ratio cylindrical nanostructures with diameters of 7 ± 1 nm. They can be readily transformed into fluids by heating and are generally thermoreversible. 1. The gels from LMWGs are typically formed by dissolution of gelator in an appropriate hot solvent and subsequent cooling to a lower temperature. At -20 oC an extremely high enantioselectivity was observed for the conversion of benzaldehyde to (R)-2-hydroxyl-2-phenylacetonitrile (97% conversion with 97% ee). addition of hydrogen cyanide to aldehydes were carried out as a gel at low temperature (-20 oC) when the solvent is toluene (Table 1). The gelator can be recycled by extraction. Cat. Cat. James Cat. the enantioselectivity is raised. Danda found that high enantioselectivity and high conversion was obtained in the hydrocyanation of 3-phenoxybenzaldehyde to (S)-2-hydroxy-2-(3-phenoxyphenyl)acetonitrile (92% and 91% ee) catalysed by the cyclo-(R)-Phe-(R)-His (2) toluene gel [48]. Cat. a b c Figure 2. Guler and Stupp synthesised peptide amphiphile 3. Cat. Following this observation. Using a cyclic dipeptide cyclo-(S)-Phe-(S)-His (1) as catalyst. Cat. the self-assembled fibrillar structure of gels was poorly understood and the gels were considered to be completely amorphous. Cat. compounds 4–6 are soluble in . In comparison. arising from self-assemble of piptide amphiphiles into nanofibres [49]. In an subsequent effort for enzyme mimicking. L Cat. Interestingly the gelation of the reaction mixture makes the degree of asymmetric induction significantly increased. L L Cat. b) gelation by coordination polymer gelators. Incorporation of catalytically active centre into gel networks (schematic representation): a) gelation by discrete gelators.1 Discrete Organogelator Supramolecular organogels based on low-molecular weight gelators are formed through reversible non-covalent interactions.1 wt% and pH above 6. Cat. A report by Inoue et al. is among the earliest reports of organogel catalysis [47]. Cat. The reaction mixture is thixotropic. c) post-modification of a preformed gel with catalytically active centre. As the viscosity of the reaction mixture is lowered.5. The dynamic nature of the system is also revealed by Escuder and Miravet that a fraction of the molecules remain in solution in equilibrium with the phase separated fibrillar material [46]. which has an important influence on the enantioselectivity. 5 5 8 5 Conv. O HN NH O R H O 1 N NH (2 mol %) HO R CN H HCN (2 equiv).4-dinitrophenyl acetate./% 97 57 83 45 97 78 99 100 100 61 88 60 73 96 44 90 60 ee/% 97 78 97 84 92 96 53 4 32 91 73 42 54 58 18 56 58 .4. Toluene. Table 1. Significantly higher catalyst activity and stability was detected for the hydrogel of 3 than the others (Figure 4). The supramolecular aggregates were subjected to hydrolysis of 2.5 2.5 6 8 0.5 8 8 1. The activity enhancement is due to higher density presentation of reactive sites with significant internal order on nanofibres relative to catalysts in solution and in spherical micelles. to 2.Supramolecular Gel Catalyst 161 water to form polydisperse spherical aggregates with diameters ca.4-dinitrophenol at 25 oC and pH 7. 15-20 nm (Figure 3). Asymmetric addition of hydrogen cyanide to aldehydes catalysed by the cyclo(S)-Phe-(S)-His (1) gel. -20 oC Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Aldehyde benzaldehyde benzaldehyde(p-OMe) benzaldehyde(m-OMe) benzaldehyde(o-OMe) benzaldehyde(m-OPh) benzaldehyde(p-Me) benzaldehyde(p-NO2) benzaldehyde(m-NO2) benzaldehyde(p-CN) 2-napthaldehyde 6-methoxy-2-napthaldehyde fufural nicotin-3-aldehyde cyclohexanecarbaldehyde isovaleraldehyde hexanal pivalaldehyde Time/h 8 10 8 10 8 10 2. a model ester compound. Toluene. 5 (C) and 6 (D) [49]. 5 oC N NH NC OH H O O 2 (2 mol %) Entry 1 2 3 4 HN N N Rate of stirring/rpm 150 200 250 300 Yield/% 97 97 97 97 ee/% 74 86 92 92 R HN H 2N O H N O HN N H N O N H O H N O N H O H N O N H O H N O N H NH2 O N H H2N 3.162 Jianyong Zhang and Stuart L. James Table 2. 4 (B). R = H R HN N H2N O H N O H N O N H N O O N O N O N H NH2 O N H H2N 4. R = H Figure 3. Influence of thixotropy in asymmetric addition of hydrogen cyanide to 3phenoxy-benzaldehydes catalysed by the cyclo-(R)-Phe-(R)-His (2) gel. R = Palmitoyl 5. 6 h. TEM images of 3 (A). . O HN NH CHO O HCN (2 equiv). R = Palmitoyl 6. 7 multiple H-bonding H interactions between n 7c. Observ ved rate increase e in hydrolysis of o 2. . 2 and EtNO2. 7c also fo orms gels in MeNO M mages of the xerogels revealed a fibrilla ar structure. L-proline derivatives 7a-c. n = 1. nd Escuder et al. a recently rep ported that a series s of L-pro oline derivativ ves 7a-c are Miravet an ca apable of self f-assembly int to organogels s in MeCN. 4. and SEM images of th he xerogels of 7c from MeNO2 and EtNO2 [50 0]. O N NH O NH N H H N H N O N H HN N NH O N NH N H O O N H O N H O H N 6 H N O H N O H N O O N H HN N O N H HN N O N H HN N H N O O 7a-c. SEM im w which are microcrystalline as demonst trated by X-ray powder diffraction (Figure ( 5).Supramolecular Gel Ca atalyst 163 Fi igure 4. ethyl e acetate or o toluene [50 0].4-dinitroph henyl acetate (H His-Omet = L-histidine m methyl ester) [49 9]. 6 n 6 H N 6 Fi igure 5. Figure 6. .5 6. is drawn to its blue form in the presence of the gel but remains yellow in the presence of a solution (Figure 6). MeCN 2 weeks. by diffusion of the aldehyde through a MeCN gel containing acetone. Table 3. -20 oC O 2N Entry 1 2 3 4 5 6 Catalyst 7a-sol 7a-gel 7b-sol 7b-gel 7c-sol 7c-gel [catalyst] sol/mM 6.6 9. In solution. Evolution of bromothymol blue color during gelation of compound 7c in MeCN.5 2. The starting yellow (not basic) solution turned into a blue (basic) gel [50].5 9. Results of racemisation of 4-hydroxy-4-(p-nitrophenyl)-2-butanone.4 2.3 1:4.2 Table 4.4 [catalyst] gel/mM 5.9 1:4. and they are basic catalysts inactive in the aldol reaction but active in the based-catalysed aldol racemisation (Table 3). OH O CHO + O2 N O Cat.4 2. James Formation of aggregates through multiple H-bonding interactions is responsible for the gel formation. An acid-base indicator dye.0 1:2.0 1:1.. Considerable basicity enhancement of L-proline secondary amine is due to proximity of L-proline groups in the gel fibres as compared to solution. bromothymol blue. 7a-c behave as enantioselective catalysts for the aldol reaction.164 Jianyong Zhang and Stuart L. whereas in the gel state. The Henry reaction of nitroalkanes and aldehydes catalysed by the 7c gel.4 2.0 1:1.6 Enantiomeric ratio (S:R) 1:4. the catalytic activity of the L-proline moiety in enamine-based aldol reactions is inhibited. Reactions were performed in the gel phase. Such a basicity enhancement leads to remarkably different catalytic activity towards the aldol reaction between acetone and 4-nitrobenzaldehyde. (10 mol %) MeCN. The results suggest that the catalytic activity of 7c can be regulated by minor temperature changes (5 and 25 oC) due to reversible sol-gel transition. It is a heterogeneous catalytic system and after . For example. The reactions in the gel phase start with the deprotonation of the nitroalkane by the secondary amine of L-proline through an ionic pair type mechanism. For catalysis for the direct aldol reaction between cyclohexanone and 4-nitrobenzaldehyde. while in solution formation of iminium intermediates may result in the nitroalkene byproducts.Supramolecular Gel Catalyst 165 CHO + R X NO2 Cat. a solution of 4nitrobenzaldehyde was left to diffuse into the gel prepared in the corresponding nitroalkane. For catalytic studies. 2 d NO2 HO R + X I X II NO2 R R + NO2 NO2 R X III Entry 1 2 3 4 5 6 7 8 R Me Me H H H H H H Reagent 4-nitrobenzaldehyde 4-nitrobenzaldehyde 4-nitrobenzaldehyde 4-nitrobenzaldehyde 4-chlorobenzaldehyde 4-chlorobenzaldehyde 4-methoxybenzaldehyde 4-methoxybenzaldehyde T/oC 5 (gel) 25 (solution) 5 (gel) 50 (solution) 5 (gel) 50 (solution) 5 (gel) 50 (solution) Yield 99 15 38 46 11 - of Yield of II + III /% 5 2 33 4 99 100 nitroaldol/% The gel phase of 7c as active phase has been shown in the Henry nitroaldol reaction between nitroalkane and aldehyde [51]. reagents were topped on the gel dissolving in toluene and the product was obtained with quantitative yield after 24 h at 5 oC with high stereoselectivity (anti: syn 92:8. 88% ee). 8 [52].g. a quantitative conversion of the aldehyde to nitroaldol was obtained in the reaction of nitroethane and 4-nitrobenzaldehyde. A sharp change in catalytic activity was observed (Figure 8). SEM revealed a network of ribbons of less than 300 nm in width and several μm in length (Figure 8). Different reaction mechanisms have been proposed for the catalytic performance (Scheme 1). Highly efficient catalytic activity for the Henry reaction was only observed in the aggregated state upon gel formation (Table 4). further designed an amphiphilic hydrogelator derived from Lproline. The reactions also work for highly and moderately reactive aldehydes (e. X-ray powder diffraction of the xerogel confirmed a lamellar structure bilayer with intercalation of the alkyl tails. 4-nitrobenzaldehyde and 4-chlorobenzaldehyde). Miravet and Escuder et al. Scheme 1. Reaction mechanism of the Henry nitroaldol reaction [51].166 Jianyong Zhang and Stuart L. . James decantation of the toluene phase the catalytic hydrogel could be reused for at least three times with similar efficiency and stereoselectivity (Table 5). Temperature controlled catalysis in the Henry nitroaldol reaction [51]. Figure 7. indicating a parrallel columnar packing (Figure 9). The MeCN gels are efficient phase transfer catalysts with stirring for Nalkylation of benzimidazole. O + 20 equip O2N CHO Hydrogel-8 (0. The catalysts can be recovered after filtration and reused after regelation with MeCN. H-bonding. . X-ray analysis. Direct aldol reaction catalysed by hydrogel-8.2 equip) Toluene-water 1 equip O OH NO2 Entry n 1 2 3 4 Ru C T/o 25 t/h 16 24 24 24 Yield/% >99 98 >99 >99 anti:syn 91:9 92:8 93:7 92:8 ee/% 18 88 87 90 1 3 st 5 5 5 2nd rd Dötz et al. Photographic and SEM images of the hydrogel of 8 [52].Supramolecular Gel Catalyst O NH N H O H N 8 167 Figure 8. reported that pyridine-bridged bisbenzimidazolium salts with long alkyl chains 1a-d efficiently gelate a variety of alcohols. SAXS and 1H NMR studies show that supramolecular interactions including π stacking between the aromatic rings. MeCN. Table 5. benzotriazole and imidazole (Table 6). and other polar solvents [53]. and van der Waals interactions between the alkyl chains are responsible for the gelation. TEM revealed morphologies of 250-500 nm wide and several micrometer long straight fibres. TEM images of the gels of 9a-d formed from i-BuOH [53]. X = I Figure 9. X = I 9d. Table 6. James N + N R X- N N X+ N R 9a. 25% NaOH MeCN. RT Ar X Ar Entry 1 2 3 4 5 6 X N N N N N CH Ar benzimidazole benzimidazole benzotriazole imidazole imidazole benzimidazole Catalyst gel 9b/MeCN gel 9a/MeCN gel 9b/MeCN gel 9a/MeCN gel 9b/MeCN gel 9b/MeCN Time/h 3 5 3 6 5 3 Yield/% 89 92 59 67 63 90 . R = n-C8H17. Phase-transfer N-alkylation of benzimidazole. (5 wt%). X Br Br + ArH cat. R = n-C12H25. R = n-C16H33. X = Br 9b.168 Jianyong Zhang and Stuart L. benzotriazole and imidazole catalysed by gel-9. X = I 9c. R = n-C16H33. DMA. MeOH. The planarity of the metal-chelating pincer ligand may allow for aggregation by intermolecular ππ interaction. while dense networks of smaller fibres result from nonprotic solvent (e. TEM images of gels formed from palladium(II) pincer complex 10 [56]. π-π stacking. sonication etc. such as H-bonding. Such gels involving weak interactions may be transformed to a fluid by external stimuli (heating.g. 10. Discrete metallogelators self-assemble through multiple noncovalent bonds. solvophobic effects. electrostatic interactions and other supramolecular weak interactions. DMSO. which can be understood to mainly form discrete complexes. enhanced by Pd···Pd interactions and van der Waals interactions between the alkyl chains. Dötz et al. + N N n-C16H33 N Pd I 10 N N n-C16H33 I- Figure 10. reported that a palladium CNC pincer Pd(II) carbene complex bearing long alkyl substituents.g. is a good gelator for normal organic solvents [56]. and THF) (Figure 10). TEM revealed that larger fibres are present in xerogels from protic solvents (e.55].Supramolecular Gel Catalyst 169 1. Promising catalytic activity of the palladium pincer carbene gel was observed in the double Michael addition of α-cyanoacetate to methyl vinyl ketone with in situ prepared DMF and DMSO gels as catalyst under slow stirring (Table 7). The metal-ligand interaction is only a secondary force to form 3D gel matrix in some sense. AcOH). Thermoreversible sol-gel transition was observed for the gels at 50–60 oC. . DMF.2 Discrete Metallogelator Discrete metal complexes have been recently reported to act as gelators [54.) to break these interactions and thus thermally reversible like their organogelator analogues. 1 10. Ligands 11a and 11b are soluble in DMSO and assemble into spherical particles with the average diameters of ca. CH2Cl2. O2 (1 atm) AcOH. 11c: R1 = Cl. and the solvent molecules plays an important role in the gelation process. The gels formed by 11c-f and Pd was used to catalyse the phenylation of indole with phenylboronic acid. 11c-Pd(II) gel.4 5. 11b: R1 = H. i + NC O CO2Et Pr2NEt.8 t1/2/h 7. R2 = OH. R2 = OH. N R1 R2 N N 11a: R1 = Me. formed by interconnection of smaller spherical aggregates. . higher than those of the soluble complex and the xerogel (less than 5% yield). RT NC CO2Et Entry 1 2 3 4 Catalyst 10-gel/DMSO (4 wt%) 10-gel/DMF (4 wt%) 10 blank k/[10-6 s-1] 24. 11e: R1 = t-Bu. 46 and 66 nm. AFM and TEM studies.9 18. H-bonding among the phenolic hydroxyl groups. lead to gelation as revealed by TEM (Figure 13). 11d: R1 = Me. 3D globular networks. The 11c-Pd(II) gel afforded the product in about 50% yield. James Table 7. examined the morphology evolution of a series of supramolecular aggregates based on dinuclear metallocyclic Pd2L2 units formed by semirigid imidazole derivatives 11a-f and Pd(OAc)2 (Scheme 2) [57]. cat. the anions.5 35 51 You et al. Double Michael addition of -cyanoacetate catalysed by gel-10. DMA. R2 = H.5 3. Whereas ligands 11c-f bearing phenolic hydroxyl groups with Pd(OAc)2 at a 1:1 molar ratio form gels in DMSO. Phenylation of indole with phenylboronic acid catalysed by 11-Pd(II) gel. revealed by dynamic light scattering DLS.170 Jianyong Zhang and Stuart L. R2 = H. respectively. R2 = OH. and other DMSO solvent mixtures. RT. 10 h N OH OH N N N N 11f H + PhB(OH)2 N H Ph N H Scheme 2. CATALYSIS BY COORDINATION POLYMER GELATORS Gels formed by coordination polymers. reported a type of polypyridine-based palladium(II) coordination polymer gels [58]. TEM and AFM height images of spherical aggregates of 14a-Pd (a. 2. are of interest considering a large number of metal ions and organic ligands available [54.f). infinitely extending metal-ligand assemblies with bridging organic ligands. the wet gel prepared from ligand 12a exhibited the optimal result. In the oxidation of benzyl alcohol to benzaldehyde on exposure to air. Metal-ligand interactions are the main driving force to form the 3D gel network as coordination polymers act as gelators. Such coordination polymer gels based on metal-ligand interactions generally can not be redissolved upon heating and do not show thermoreversible gel-sol transitions.b. Reactions of polypridine ligands 12a and 12b with Pd(OAc)2. and TEM image of the 14e-Pd xerogel obtained from DMSO [57].Supramolecular Gel Catalyst 171 Figure 13. Xu et al.55].c) and 14b-Pd (d.e. giving a total catalytic . 12c with Pd(OAc)2 or [Pd(en)(H2O)2](NO3)2 in DMSO gave metallogels after 4 h ~ 2 months which did not flow on inversion of the vial. 172 Jianyong Zhang and Stuart L. James turnover (72) about twice that of Pd(OAc)2, and three that of the corresponding precipitate from acetone (Scheme 3). OH OHOH OH N N N NH N HN N N N N NH HN N 12c CHO N N HN N N 12a N N N 12b OH 12-Pd(II) gel (0.1 mol %) air, 90 oC, 2 h Scheme 3. Aerobic oxidation of benzyl alcohol catalysed by the 12-Pd(II) gels. A larger tripyridine ligand 13 was later reported by our group to form coordination polymer gels with Pd(COD)(NO3)2 in a range of mixed organic solvents (e.g. MeOH-CHCl3) [59]. The gels can be formed with a range of Pd/13 ratios from 1:1 to 1:4 during a shorter period of 2 min to 2 h. 1H NMR, FT-IR, and fluorescence spectroscopic studies showed a combination of Pd-N coordination, H-bonding, π-π stacking being present in the gel aggregates. SEM revealed an interesting morphology evolution of spherical assemblies to fibrous structures in the xerogels with decreasing Pd/13 ratios from 1:1 to 1:4 (Figure 11). The 13-Pd(II) gel/xerogels efficiently catalyse the Suzuki-Miyaura coupling under atmospheric conditions (Table 8, entries 1–4). Interestingly, the fibrous network has been shown to have higher activity than spheres in Suzuki-Miyaura coupling. The xerogel catalyst can be recovered by simple filtration for at least 5 times and reused without significant loss of activity. N HN O 1/4 equiv Pd 2+ 1 equiv Pd2+ N N N H N O N O NH N 13 Figure 11. Morphology evolution of Pd-pyridyl gels depending on Pd/L ratio. The gel nanofibres based on the Pd-13 gel can be supported on superparamagnetic magnetite (Fe3O4) nanoparticles by simply mixing 13, and Pd2+ in CHCl3-MeOH with a Pd/13 molar ratio of 1:1 in the presence of magnetite nanoparticles [60]. The presence of magnetite nanoparticles was unambiguously confirmed by TEM and magnetism studies (Figure 12). Supramolecular Gel Catalyst 173 The superparamagnetic 13-Pd(II)-MNPs xerogel show similar activity in Suzuki-Miyaura CC coupling reactions (Table 8, entries 5–8). The xerogel can be magnetically isolated with a permanent magnet and reused for 5 times in the reaction of iodobenzene and phenylboronic acid. Table 8. Suzuki cross-coupling of aryl halides and phenylboronic acid catalysed by the 13-Pd(II) (1:1) gel and the 13-Pd(II)-MNPs xerogel. R X = I, Br X + 1.5 equip B(OH)2 13-Pd(II) gel (1 mol %) 3 equip Na2CO3, MeOH, 60 oC R Entry 1 2 3 4 5 6 7 8 X I Br Br Br I Br Br Br R H H COMe OMe H H COMe OMe Catalyst 13-Pd(II) gel 13-Pd(II) gel 13-Pd(II) gel 13-Pd(II) gel 13-Pd(II)-MNPs xerogel 13-Pd(II)-MNPs xerogel 13-Pd(II)-MNPs xerogel 13-Pd(II)-MNPs xerogel Time/h 90 15 15 15 120 60 15 30 Magnetic gel Yield/% >99 28 >99 26 >99 78 97 27 N HN O + N N N O 13 H N N Pd2+ + Fe3O4 mixed O NH N product substrate a Figure 12 (Continued). b 174 Jianyong Zhang and Stuart L. James c d Figure 12. Magnetic gel nanofibres for organic transformation, and TEM images of the 13–Pd(II) xerogels before (a,b) and after (c,d) loading of magnetite nanoparticles [60]. Uozumi et al. reported a palladium-based coordination polymer gel based on a tripodal flexible triphosphine 14 [61]. A yellow gel is obtained upon reaction of 14 with PdCl2(NCPh)2 in toluene at 100 oC for 24 hours. 31P MAS NMR of the gel showing a singlet at 20.0 ppm is consistent with complexation of palladium species and the ligands through PdP coordination bonding. The xerogel is insoluble in water and several types of organic solvents (chlorinated solvents, toluene, methanol). The xerogel’s catalytic ability was investigated in the Suzuki-Miyaura coupling of aryl halides with boronic acids in water. High yields of coupling products were obtained and Electron-deficient as well as electron-rich aryl iodides/bromides readily coupled with arylboron reagents bearing para-, meta-, and orthoEWG and EDG substituents to give the corresponding biaryls in 80-99% yields. The catalyst could be recycled at least four times with retention of similar activity as demonstrated in the reaction of iodobenzene with 4-tolylboronic acid (Scheme 4). PPh2 O 6 O O O 6 O Ph2P I + (HO)2B 1.5 equip O 6 14 PPh2 14-Pd(II) xerogel (0.05 mol %) 3 equip Na2CO3, H2O, 3 h, 100 oC 1st use: >99% (GC yield) 2nd use: 91% (GC yield) 3rd use: 95% (GC yield) 4th use: 90% (isolated yield) Scheme 4. Suzuki cross-coupling catalysed by the 14-Pd(II) xerogel Supramolecular Gel Catalyst N N 175 n RO RO 15a: R = CH2OCH3, n = 1 15b: R = CH2CH3, n = 1 15c: R = n-C6H13, n = 1 15d: R = n-C6H13, n = 2 n N N Figure 13. SEM image of the 15a-Cu(I) xerogel [62]. Table 9. Huisgen 1,3-dipolar cycloaddition catalysed by the 15–Cu(I) xerogels. N3 15-Cu(I) xerogel (1 mol %) H2O, RT, air N N N R + R 1.2 equip Entry 1 2 3 4 5 6 7 8 9 10 R Ph Ph Ph Ph Ph p-Tol m-Tol 2-Py TMS n-Bu Catalyst 15a–Cu(I) 15b–Cu(I) 15c–Cu(I) 15c–Cu(I) 15d–Cu(I) 15c–Cu(I) 15c–Cu(I) 15c–Cu(I) 15c–Cu(I) 15c–Cu(I) Time/h 18 18 18 8 18 18 18 18 18 18 Yield/% 78 73 100 97 97 95 100 100 12 8 Bian and Gao et al. investigated chiral binaphthylbisbipyridine-based copper(I) coordination polymer gels [62]. Equimolar 15a-d and Cu(MeCN)2BF4 in hot MeCN-CH2Cl2, MeCN-THF, or MeCN-dioxane (v/v, 1/1) form gels on cooling to RT. SEM revealed that the existence of nanofibres are responsive for the gelation (Figure 13). Formation of 1D coordination polymer of tetrahedral Cu(I) ions and the ligands at a ratio of 1:1 is necessary for the gelation as indicated by 1H NMR, UV-vis and CD spectroscopy. DSC analysis showed the 15a-Cu(I) gel has no endothermic transition up to 100 oC. π-π stacking interaction between the 1D coordination polymers was revealed by UV-vis spectroscopy. Cu(I) is significantly stabilised by the gel network with an increase of 1.20 V for the redox potential of Cu(I)/Cu(II) of 15c-Cu(I) compared to Cu(I)(2,2'-bipyridine)2. The catalytic activity of the 176 Jianyong Zhang and Stuart L. James 15–Cu(I) xerogels was explored in the Huisgen 1,3-dipolar cycloaddition (“click” reaction) (Table 9). The 15c–Cu(I) xerogel gave optimal result in the reaction of benzyl azide and phenylacetylene with quantitative conversion in water at RT. The xerogel catalyst can be easily separated from the reaction mixture, and the recovered catalyst could be used for consecutive reaction for three times without significant loss of activity. 3. CATALYSIS BY POST-MODIFIED GELS Loading of catalytically active centres to a preformed functionalised organogel or metallogel is another strategy to produce a gel catalyst. Miravet and Escuder reported pyridine-functionalised organogels. Dipyridine ligands based on amide linkages with stereospecific attachment of isopropyl groups, 16a and 16b, efficiently gel H2O and a variety of organic solvents including toluene (Scheme 5) [63]. Intermolecular mutiple H-bonding similar with that present in 7c is the driving force for gelation. The toluene gels could be postmodified by complexation of Pd(II) ions to from Pd-N(pyridine) coordination bond for catalytic activity. A solution of Pd(OAc)2 in toluene was layered on top of the gel and was observed to diffuse into it. Evidence for incorporation of palladium into the actual fibres of the gel was obtained from TEM, since no metal shadowing was required to image these fibres (Figure 10). Metal-complexation could help reinforce H-bonding organogel fibres to obtain mechanically robust gels. The Pd(II)-immobilized gel showed catalytic activity for the oxidation of benzyl alcohol to benzaldehyde at 65 oC with a maximum yield of 50% (10 turnover numbers) after 48 h. O N N H O 16a H N H N O O N H N N O N H O H N 16b H N O O N H N OH 16-Pd(II) gel (5 mol %) toluene, air, 65 oC, 48 h CHO Scheme 5. Aerobic oxidation of benzyl alcohol catalysed by the 16-Pd(II) gels. A very simple method for formation of a coordination polymer gel involves reaction between Fe(NO3)3·9H2O and the 1,3,5-benzentricarboxylic acid (H3BTC) in ethanol [64]. The gel forms within a few minutes, is stable to a range of solvents but dissolves in aqueous hydrochloric acid. The Fe3+ gel is potentially useful since it also forms in the presence of methylmethacrylate, which can be polymerised to give PMMA and the gel template removed with aqueous HCl. This leaves the organic polymer imprinted with the original gel structures. Accordingly SEM showed this PMMA to have a sponge-like structure with pores in the size range 1-10 μm (Figure 15). With the gel as template, macroporous poly(glycidyl methacrylate-co-ethylene glycol dimethacrylate) was fabricated to show promise in chromatographic separation of protein [65]. Recently, Kaskel et al. investigated the Supramolecular Gel Catalyst 177 adsorption properties of the Fe(III)-carboxylate gels. Their aerogels have highly porous nature with a combination of micro- and macroporosity (total pore volume 5.62 cm3 g-1 and BET surface area 1618 m2 g-1), which are promising as catalysts or catalyst supports [66]. Figure 14. TEM images of the xerogels of 16b before modification with Pt-shadowing (A) and after modification with Pd(OAc)2 with no shadowing (B, C) [63]. Figure 15. SEM images of spongelike PMMA templated by the Fe(III)-BTC gel [64]. 17 78 Jianyong Zha ang and Stuart L. James H HOOC PPh2 H HOOC H HOOC 17a CO OOH HOOC N H3BT TC COOH HOOC N H 17b Sc cheme 6. Bridging carboxylate e acids for meta allogels. For catalys sis, the Fe-BT TC gel has been b modified d with differe ent functional groups to ob btain a ran nge of func ctionalised Fe-gels F based d on dicarb boxylic acid, e.g. 5di iphenylphosph hanylisophtha alic acid (17a a, Scheme 6) ) [67]. Gels could be for rmed when m mixing of the solutions of 17a and Fe( (NO3)3·9H2O in alcohols and a DMF. SE EM of the xe erogels reveal led globular or r block-like morphologies m o 2-10 μm fo of orming an inte erconnected po orous network k (Figure 16a a,b). The pho osphine-functi ionalised gel with phospho orus donor av vailable for fu urther coordin nation has pro omising cataly ytic application ns for post-m modification w catalytical with lly active cent tres. After loa ading of Pd(II) ), the gel show wed efficient catalysis c in th he Suzuki–Mi iyaura cross–coupling of aryl a halides/b bromopyridine es with variou us boronic ac cids under am mbient atmosp phere (Table 10). 1 The phos sphine gel sho ows potential to act as a ne ew type of fun nctionalisable porous scaffo old, and the ge el could be eas sily recovered and reused fo or subsequent t reactions, e.g. the coupl ling of 4-bromopyridine with w 3,5-diflu uorophenylbo oronic acid. a b c d Fi igure 16. SEM and TEM images of the Pd(II) modified 17a– –Fe(III) (a,b) an nd 17b–Fe(III) (c,d) xe erogels [67,68]. . Supramolecular Gel Catalyst 179 Table 10. Suzuki–Miyaura cross–coupling of aryl halides/bromopyridines with boronic acids catalysed by the Pd(II) modified 17–Fe(III) gels. 17-Fe(III)Pd(II) gel (0.5 mol %) 3 equip Na2CO3 MeOH, 60 oC R X = I, Br X + B(OH)2 1.5 equip R Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Catalyst 17a-FePd gel 17a-FePd gel 17a-FePd gel 17a-FePd gel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd gel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd xerogel N + Br PyBr R R B(OH)2 X I Br Br Br I I Br Br Br Br Cl Cl Cl Cl R H H OMe COCH3 H H H COCH3 OCH3 OCH3 H H COCH3 COCH3 Time/h 1.0 0.5 1.0 1.0 0.5 0.5 0.25 0.5 0.5 1.0 11 0.5 1.0 3.0 N R Yield/% 100 71 35 99 >99 >99 91 >99 72 69 46 8 14 12 17-Fe(III)Pd(II) gel (0.5 mol %) 3 equip Na2CO3 MeOH, 60 oC R Entry 15 16 17 18 19 20 21 22 23 24 25 26 27 28 Catalyst 17a-FePd gel 17a-FePd gel 17a-FePd gel 17a-FePd gel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd xerogel 17b-FePd gel 17b-FePd gel 17b-FePd xerogel 17b-FePd xerogel PyBr 4-bromopyridine 4-bromopyridine 3-bromopyridine 2-bromopyridine 4-bromopyridine 4-bromopyridine 3-bromopyridine 3-bromopyridine 2-bromopyridine 2-bromopyridine 4-bromopyridine 3-bromopyridine 3-bromopyridine 2-bromopyridine R F H F F Me Me Me Me Me Me F F F F Time/h 2.0 1.0 3.0 2.0 1.0 1.25 0.5 2.0 6.0 1.0 3.0 27 5.0 2.0 Yield/% 95 >99 71 52 >99 >99 >99 77 86 30 58 93 8 16 The coordination bond (e.g. Fe-N bond) present in metallogels has been employed to immobilise active catalysts resulting from the dynamic nature [68]. A bifunctional ligand, 51H-benzo[d]imidazole-1,3-dicarboxylic acid (17b, Scheme 6), forms coordination polymer gels with Fe3+ in DMF-H2O, DMF, and DMF-MeOH. The xerogels have an interconnected 180 Jianyong Zhang and Stuart L. James porous network of globular nanometer-sized particles of ca. 100 nm, as indicated by SEM and TEM (Figure 12c,d). In the gels, the hard metal ion Fe3+ strongly coordinates to carboxylate groups to form the gel network, and Fe3+ may also coordinate to the imidazole group less strongly. When Pd2+ is loaded, binding of softer Pd2+ via the imidazole N atom is more favourable resulting in cleavage of Fe–N(imidazole) bond and generation of new Pd–N bond due to their different binding ability. Compared with its homogeneous analogue, the Pd(II)modified coordination polymer gel exhibited significantly improved activity in the Suzuki– Miyaura cross–coupling (e.g. coupling of phenylboronic acid and 4-bromoanisole), and could be reused for several times (Table 10). CONCLUSION Gels are a type of aggregates between highly ordered aggregates (crystals) and random aggregates (amorphous solid). Its particular complexity of gels has been shown in literature. The actual molecular structures of most gels are still beyond current techniques. The results of crystal engineering help understand the structure of gel network, but it is still far from the final structure. Supramolecular interactions between gelators, between liquids, and between gelator and liquid have not been fully understood yet. The rational design, especially of catalytic gelators, is still in infancy. As shown above, supramolecular gels provides an interesting, useful and increasingly important medium in which to investigate and exploit catalytic chemistry, and indeed the chemistry and physics of active catalytic centres in general. The examples described in the chapter demonstrate that unique new catalytic properties can arise from combining gels with catalytically active centres. 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ABSTRACT With its promising physical and chemical properties. catalysis. Poehler ISBN: 978-1-61122-894-6 © 2011 Nova Science Publishers. and supercritical carbon dioxide or through distillation. recyclable liquid that is manufactured from renewable sources and that facilitates the dissolution of organic substrates.ac.il. catalyst recycling. homogeneous catalysis. Chemical Engineering Department. ethyl acetate. Polar and nontoxic. glycerol was used as both solvent and reactant. in * Corresponding author. "greener") industrial process in which energy and waste are minimized and costs are reduced is of universal concern. Beer-Sheva. INTRODUCTION The need for an efficient.. Chapter 6 GLYCEROL AS A SUSTAINABLE SOLVENT FOR HOMOGENEOUS CATALYSIS Adi Wolfson*. Furthermore. Christina Dlugy and Dorith Tavor Green Processes Center. Sami Shamoon College of Engineering. Glycerol also enabled easy isolation of the reaction product either by extraction with glycerol immiscible solvents such as diethyl ether. low energy. Email: adiw@sce. in many reactions. and clean (i. the use of glycerol as a solvent promoted improved activities and selectivities of the reactants.e. in certain reactions such as the catalytic transfer-hydrogenation of various unsaturated organic compounds and the transesterification of alcohols. Keywords: Glycerol. glycerol can be used as a sustainable solvent in many catalytic and non-catalytic organic reactions. the harsh conditions often present during product distillation may lead to product or catalyst decomposition. Organic chemistry is typically carried out in solution to dissolve reactants and/or homogeneous catalysts and usually requires large amounts of solvent [5]. Furthermore. and biological natures of a solvent are of paramount importance in any process that involves mass. In addition. Extraction of the products using an additional solvent. Alternative Reaction Media Reaction solvent suitability also depends on. The chemical. and its physical properties may dictate the reaction conditions [5]. distillation is usually not applicable. with its ideal environmental impact. ionic liquids. and in dilutions. or momentum transfer [1. 4]. improving reaction selectivity in catalytic processes helps reduce the formation of byproducts and thus leads to simpler. When the addition of an extraction solvent is necessary. the chosen solvent should have minimal volatility and it should be chemically and physically stable. cleaner. and reusable. either reaction or extraction. relatively low . In addition. Traditionally employed in the majority of chemical processes. in addition to its solubility and environmental friendliness. extraction solvent selection should also be based on how it affects the environment.. and solids) must be taken into account. and the ease of subsequent separations. petrochemical solvents have severe implications for the environment. fluorous solvents. Catalysis also plays an important role in the prevention of waste generation in organic synthesis [6-8]. therefore. As such. Safety and the environment are also primary concerns in the selection of a solvent [3. recyclable. Christina Dlugy and Dorith Tavor separation procedures. would involve substrates that are fully or partially miscible in the reaction phase and products that are poorly miscible. catalysis can eliminate the need for toxic reagents. Solvent characteristics also dictate the most effective separation method for product recovery [13]. catalytic reactions are usually performed under milder conditions resulting in lower energy consumption. using a biodegradable solvent from a renewable resource such as plants is preferable. and supercritical fluids. including water. Furthermore.186 Adi Wolfson. the reaction solvent should be immiscible with a variety of other solvents. Hence the search for environmentally friendly reaction mediums is of primary interest. is a feasible alternative. and more effective separation processes [9-12]. worker safety. A variety of environmentally benign solvent alternatives has been proposed in the literature. suffer from cross-contamination of the liquid phases. an undesired result that necessitates additional downstream separation. the solubilities of the reactants (gases. Although commonly used to recycle catalysts [11]. 2]. liquids. When a solvent is used as part of the reaction media. whether it is a sustainable solvent. Water. The chemical composition of the solvent can also affect reaction activity and selectivity. as it combines several transformations into single steps. In some reactions. whether it promotes easy product separation and catalyst recovery. A solvent with a relatively high boiling point would allow distillation of more volatile products. heat. many biphasic catalytic systems. i. physical. Moreover. which would form a two-phase (biphasic) system with the reaction solvent.e. but when large organic products are involved. The ease with which the product can be separated from the costly soluble metal catalyst for the latter to be recycled is often the determining step for large-scale implementation. The ideal system for simple separations without the addition of an extraction solvent. solvent decomposition at high temperatures may yield hazardous compounds. 31]. Its relatively low critical pressure and temperature (Tc=31°C.or biphasic catalytic systems in a variety of organic reactions with and without TMCs and enzymes. separations can be . 22].g. viscosity. to name but a few. increasing attention has been focused on ionic liquids (ILs) as alternative green solvents due to their unique and versatile physical and chemical properties [17-20]. 16]. and large amounts of hazardous and volatile organic solvents are utilized in their production.Glycerol as a Sustainable Solvent for Homogeneous Catalysis 187 price. Supercritical and compressed fluids—especially supercritical carbon dioxide (scCO2)— represent another potential class of green solvents. Pc= 74 bar) together with its low toxicity and environmental impact and affordable price make it an even more attractive solvent candidate. Supercritical fluids are substances above their critical temperature and pressure [23-25] and represent a highly tunable solvent class. In addition. Although this system enables the TMCs to be separated and recycled. they have negligible vapor pressure and thus do not contribute to airborne pollution. Furthermore. Composed of ions.. ILs have already been used in numerous mono. Organic and catalytic reactions in mixtures of paraffin with fluorinated solvents have also been reported in the literature [15. a characteristic that can completely eliminate common interfacial mass transfer limitations. scCO2 is now widely used in extraction and purification processes in the petrochemical. their chemical and physical properties and toxicology and safety measurements are not completely known [21. Water-organic biphasic systems were thus employed to solve solubility limitations and to recycle transition metal complexes (TMCs). The reactants and catalysts with specialized ligands are in one homogeneous phase. have also been reported as green solvents for catalysis. H2. and reasonable boiling temperature. even though they can be recycled and re-used. and pharmaceuticals industries [30. However. Separation of the products and recycling of the catalyst were accomplished by distillation or extraction with a non-miscible solvent. O2. diffusivity. While ILs are potentially green. etc. CO2 can be miscible with reaction gases (e. Ionic liquids are organic salts that are liquid near ambient conditions (Tm < 100 °C). In addition. the reaction is single phase if performed at the reaction temperature while a temperature decrease leads to a two-phase system. CO2 from non-sequestered sources represents an environmentally benign and non-toxic solvent for reaction. and. are possible. large changes in properties like density.). and thermal conductivity. the widespread use of ILs as reaction media has been thwarted by their considerable drawbacks. compressed fluids represent many solvents in one compound. This sensitivity allows for the precise selection of the desired properties for any given reaction with supercritical fluids. Because supercritical fluids are extremely sensitive to pressure and temperature. The relatively high price of most ILs will prevent them from being used as solvents in large-scale processes. food. Moreover. they must undergo tedious modification prior to their use in the reaction. as such. especially scCO2. extraction. Nevertheless. In these systems. CO. reactions run in biphasic systems are usually accompanied by mass transfer limitations. some ionic liquids have low biodegradability. mainly due to their low vapor pressure. but the negligible solubility of many organic compounds in water can cause low reaction rates [14]. the water crisis currently facing the entire planet is liable to increase the price and decrease the availability of water for industrial applications. Used for years for analytical or extraction purposes. and material processing [26-29]. is an attractive solvent. Supercritical fluids. Recently. However. whether as a reactant or as an additive. etc. dispersing medium. products. . cosmetics. These qualities make it suitable for use as a humectant. Based on the above-mentioned specifications for an environmentally friendly solvent.and aromaticsfree and since it is obtained from renewable resources. Christina Dlugy and Dorith Tavor achieved via changes in the temperature or pressure. which is a high value chemical in the synthesis of polyesters [36. i. and recyclable liquid that is highly inert and stable. economical ways of glycerol utilization must be explored to further defray the cost of biodiesel production. Glycerol is the main by-product from the conversion of oils and fats in oleochemical production (Figure 1) [32. glycerol yielded ethanol and hydrogen [39]. biodiesel. biodegradable. thickener. its price has substantially decreased due to an increase in supply from the production and use of fatty acid derivatives in the food. and food products. personal care. emollient. And as increasingly greater quantities of glycerol are generated by the biodiesel industry. However. and drugs industries and in biofuel synthesis. toiletries. Glycerol also forms the raw material in chemical syntheses [34] such as the production of dendrimers and hyperbranched polyethers and polyesters [35]. Transesterification of triglycerides.. OCOR1 OCOR2 OCOR3 Triglyceride Alcohol ROCOR1 OH + Catalyst 3 ROH + ROCOR2 + OH OH + ROCOR3 Mixture of alkyl esters Glycerol Figure 1.) and is used as an ingredient or processing aid in cosmetics. plasticizer. 37]).3-propanetriol). and catalytic oxidation to form various commercially important compounds such as dihydroxyacetone and glyceraldehydes [38]. bodying agent. lubricant.2.188 Adi Wolfson. glycerol derivatives such as glycerol esters are also extensively used in many industries. it is often difficult or uneconomical to render reactants. antifreeze. In the past decade. and especially metal complex catalysts soluble in the supercritical fluid phase. 33]. glycerol (glycerin. has a high potential of fulfilling the requirements of a green solvent. drugs.e. widely available and inexpensive. catalytic hydrogenolysis to propylene glycols (especially 1. A non-toxic. in all applications. Used as an energy source for microorganism fermenting systems. sweetener. As such. Indeed. glycerol is compatible with many other chemical materials. the biodiesel market is growing rapidly as it is sulfur. glycerol is used principally as a highly refined and purified product. glycerol has been approved for food and drug use by many government agencies (US FDA. 1. In this review we will explore the scope and limitation of using glycerol as a sustainable reaction medium in organic transformations. In addition. and processing aid.3-propanediol. it is compatible with most organic and inorganic compounds. ionic liquid [1-butyl.66 No ~5000 Tedious NBP(°C) Vapor pressure at 50°C (mmHg) Dielectric constant (25°C) Viscosity (cP) (30°C) Density (g/mL) Biodegradability LD50 (Oral-Rat) (mg/Kg) TMCs modification a BmimPF6= 1-butyl-1-methylimidazolium hexafluorophospate. and Shotland reported several years ago for the first time about the use of glycerol as a reaction medium in both catalytic and non-catalytic organic syntheses [40]. which are immiscible in glycerol.51 78. glycerol has been successfully employed as a green solvent in a wide variety of organic reactions and synthesis methodologies. its unique chemical.5 629 1. water. the production of glycerol is a simple transesterification (Figure 1) process that is not associated with the use of a toxic reagent or the production of large amounts of toxic waste as with other green solvents. acids and bases. its availability is high and its price is low. and perfluorohexane (tetradecafluorohexane) as the representative fluorocarbon solvent are summarized in Table 1. showing its versatility as a solvent for organic synthesis (Table 2).5 1 1 >90000 Minor BmimPF6a >300 <1 11. Dlugy. physical.37 No ~1500 Without C6F14 58-60 n. high product yields and selectivities were achieved.a 1. A comparison of several relevant properties of glycerol. but it also dissolves organic compounds that are poorly miscible in water and it is non-hazardous. it boasts additional properties that grant it superiority over alternative green solvents. . Hydrophobic solvents such as ethers and hydrocarbons.a. because glycerol is produced as a by-product of the constantly expanding oilbased chemical industries. Table 1. Wolfson. First. enzymes and TMCs.4 312 1. glycerol is suitable in homogeneous and heterogeneous chemo. In short.Glycerol as a Sustainable Solvent for Homogeneous Catalysis 189 2. Product distillation is also feasible due to the high boiling point of glycerol.29 Yes 12600 Without/ minor H2 O 100 92. It has a very high boiling point and negligible vapor pressure. Like other polar organic solvents such as DMSO and DMF. enable reaction products to be simply extracted.and bio-catalyst systems as well as in catalyst free systems. In addition to the characteristics that confer upon glycerol its potential for use as a green reaction medium. and it does not require special handling or storage. GLYCEROL AS A SUSTAINABLE REACTION MEDIUM Glycerol's physical and chemical properties hint at its promise to be used as a green solvent. <5 n. Indeed. Since then. 3methylimidazolium hexafluorophosphate (BmimPF6) as a representative commercial and commonly used IL]. and in most of the reactions. Based on all the advantages outlined above. In addition. glycerol dissolves inorganic salts. and biological properties make glycerol an exceptionally safe solvent. Properties of alternative green solvents [40] Glycerol 290 <1 42. 45 10 Suzuki coupling 44 11 12 13 14 15 16 Aldol condensation Electrophilic substitution of indoles Ring opening of epoxides Knoevenagel-type reactions β. 51 17 Hydrogenation 40. β-diarylation of acrylates Transfer hydrogenation-dehydrogenation 45 46 47 47 48 50. 49 . 55 18 Asymmetric reduction 19 Dimerization 20 Michael reactions Homogeneous and heterogeneous bio-catalysts 21 Asymmetric reduction 22 Trans-esterification (kinetic resolution of racemate) 40. Rhizopus oryzae Novozyme-435 Reference 40 40. Christina Dlugy and Dorith Tavor Table 2. 44. Organic reactions in glycerol Entry Reaction Non Catalytic 1 Nucleophilic substitution 2 Reduction of carbonyls 3 aza-Michael reactions 4 Michael reactions 5 Ring opening of epoxide 6 Electrophilic activation of aldehydes 7 Wolff-Kishner reduction of benzaldehyde 8 Electro reduction of benzaldehyde Homogeneous and heterogeneous chemo-catalysts 9 Heck coupling Catalyst Pd(OAc)2 Pd(OAc)2(TPPTS)2a PdCl2 PdCl2(TPPTS)2a PdCl2(DPPF)2b Pd/C Pd(OAc)2 Pd(OAc)2(TPPTS)2a PdCl2 PdCl2(TPPTS)2a PdCl2(DPPF)2a Pd/C KOH CeCl3*7H2O Bases Bases Pd/APc Ru(p-cumene)Cl2-dimer RuCl2(TPPTS)3a Ru/C Pd/C Raney-nickel RhCl2(TPPTS)3a Pd/C Ru-BINAP [C8Mim]NTf2d KF/Alumina Free and immobilized bakers yeast. 43. Aspergillus terreus. 43 43 41 52 40. 43 41 41 41 42 43 43 40. 53.190 Adi Wolfson. 54. entry 3. can dissolve a variety of compounds. [41]). entries 1-8). d [C8Mim]NTf2= 1-methyl-3-octyl imidazolium bis[trifluoromethylsulfonyl]amide. Another example of the advantage of using glycerol (as a polar reaction medium) instead of water and DMSO was demonstrated by Gu and Jérôme in the catalyst-free azo-Michael reaction between p-anisidine and n-butyl acrylate (Figure 2b. Glycerol. Similarly. which is negligible in water. but as a natural. Many organic reactions also require the dissolution of salts and organic compounds or hydrophilic and hydrophobic molecules simultaneously. it should be able to dissolve solids. or glycerol. In the same report. was augmented in the organic solvents (Table 3.1'-Bis (diphenylphosphino) ferrocene). b DPPF= [1. In this reaction. A solvent should facilitate the combination of reactants and catalysts. One of the first examples of organic transformation in glycerol that exploits its ability to dissolve a non-polar organic compound and a polar ionic salt together is the nucleophilic substitution of benzyl chloride with potassium thiocyanate [40]. Gu and Jérôme also studied the catalyst-free ring opening of styrene oxide with p-anisidine (Figure 2c. c Pd/AP= palladium nanoparticles stabilized over sugar-based surfactant. The authors assumed that the different behaviors observed for water and glycerol arose from the better affinity of p-anisidine for the glycerol interface. when glycerol is used. Separation of product at the end of the reaction was done by extraction with diethyl ether followed by evaporation of the extracting solvent under reduced pressure [40]. Solubility of Reactants and Products in Glycerol The key property of a reaction solvent is its solvation capability. liquids. entry 2. which produced about 20% water and soap. but it also facilitates the separation of many organic molecules by simple extraction with glycerol immiscible solvents. the solubility of the reaction product in the reaction medium and the nature of the solvent also dictate separation technique. yielded large amounts of product in the glycerol. Several catalyst-free organic transformations were performed in glycerol using its ability to dissolve both organic and inorganic molecules (Table 2. less hazardous extraction solvents can be used because glycerol is immiscible with a variety hydrophobic solvents. was also tested in the same reaction and yielded similar amounts of product. On the other hand. At the end of the reaction the product was removed by extraction with ethyl acetate after which the glycerol was re-used twice.Glycerol as a Sustainable Solvent for Homogeneous Catalysis a 191 TPPTS= tris-(3-sulfophenyl)-phosphine trisodium salt. which is usually . [41]). or DMSO for comparison and illustrates the beneficial use of glycerol as a reaction solvent. entry 1). and gases as required. DMSO. Moreover. since the solubility of benzyl bromide. green organic solvent. The reaction. The yield of benzyl acetate in DMSO was higher then in glycerol. and as such. which showed no product in the DMSO and only trace amounts of product in the water. thus inducing a faster reaction rate compared to what was observed with water. biodegradable. glycerol is preferable. It should be maintained that although the addition of extraction solvent makes the procedure "less green". The second and third reaction runs returned comparable product yields. a polar organic solvent. Table 3. Table 3 summarizes the yields of several representative catalyst-free reactions in glycerol. using crude glycerol from the transesterification of oil (Figure 1). the nucleophilic substitution of benzyl bromide with ammonium acetate (Figure 2a) was run in water. Table 3. and the reactions in both organic solvents were faster than that in water. water. Employing crude glycerol as a solvent has definite environmental and economical advantages as it does not require tedious purification after alcoholysis. c) Ring opening of styrene oxide [41]. the reaction in either water or glycerol proceeded successfully. in terms of selectivity. Table 3. Moreover.192 Adi Wolfson. reactions that usually include acid catalyst were run in glycerol under catalyst-free conditions. not only was the product yield in glycerol higher than in water. Catalyst-free reactions in glycerol: a) Nucleophilic substitution. Br OAc a) + NaOAc + NaBr NH2 O b) OMe H N O c) NH2 MeO a H N MeO b CHO d) NO2 H N O MeO O O + OH + OMe OH H N + 2 N H N H Figure 2. entry 4. glycerol was also shown to perform well. in addition to the green nature and production process of . [42]). even without a catalyst. Christina Dlugy and Dorith Tavor acid-catalyzed. as the regioselectivity obtained in glycerol was higher than that for water. but it also resulted in a glycerol insoluble solid that was easily isolated by filtration. In the reaction between 4-nitrobenzaldehyde and 2-methylindole. d) Electrophilic activation of nitrobenzaldehyde [42]. The electrophilic activations of aromatic aldehydes were also reported to proceed better in glycerol than in water or in different organic solvents (Figure 2d. The examples discussed above illustrate the flexibility of glycerol as a reaction solvent that facilitates both the dissolution of a range of organic and inorganic compounds and simple product separation. b) aza-Michael reaction [41]. Furthermore. Again. b) Suzuki cross-coupling of halobenzene and phenylboronic acid [44]. 1. TMCs in biphasic systems are frequently heterogenized to combine the advantages of homogeneous and heterogeneous catalysis [11].and bio-catalysts (Table 2. 1.0 mmol p-Anisidine. Catalyst-free organic transformations in polar solvents Product yield (%) Reaction Nucleophilic substitutiona aza-Michaelb.0 mmol butyl acrylate. The reaction procedure in glycerol is therefore cleaner as it is more material and energy efficient. the formation of by-products can be reduced. A variety of catalytic reactions were run in glycerol using homogeneous and heterogeneous chemo. 20 h. b Reaction conditions: 1. One of the first examples of a .8 mmol benzyl bromide.[41] Electrophilic activation of aldehydese. Heterogeneous catalysts have the distinct advantage that they can be easily separated and re-used while homogeneous catalysts are usually very specific.Glycerol as a Sustainable Solvent for Homogeneous Catalysis 193 glycerol compared to other green alternative reaction mediums. base + R a) X=Br. entries 9-22). 20 h. [42] a Water 38. As a result. In fact. Heterogenization of Metal Catalysts in Glycerol Catalysts are required for many organic reactions to proceed. its use as a solvent also permitted running several reactions without catalyst and yielded higher activities and selectivities. 70 °C.88 mmol ammonium acetate. I R + Glycerol HX X B(OH)2 b) Pd catalyst. 0.e Reaction conditions: 90 °C.0 mmol. leading to simpler.1 <5 88 (a/b=76/24)d 76 DMSO 100 0 0 <5 Glycerol 60. Therefore. 5 ml solvent. the inclusion of which may enable toxic reagents to be replaced and may improve reaction activity and selectivity. a) Heck coupling of halobenzene and activated olefin. c Reaction conditions: 1. 1 mL solvent. cleaner. 1 h. X Pd catalyst. 100 °C. and selective. 100 °C. butyl acrylate. 3 h. the development of environmental friendly processes often rely on catalysis.[41] Ring opening c.0 mmol p-Anisidine. base + Glycerol X=I. 1 mL solvent. d Regioselectivity as presented in Figure 2c. Cl Figure 3. and more effective separation processes [6-9].3 82 85 (a/b=93/7)d 95 Reaction conditions: 0. Br. Table 3. active. [44]). Palladium salts and complexes and supported palladium catalyst were used together with organic and inorganic bases as co-catalysts (Table 4). but using 20 g glycerol. c 1h. Palladium-catalyzed Heck and Suzuki coupling of iodobenzene with butyl acrylate and phenylboronic acid in glycerola [44] Entry 1 2 3 4 5 6 7 8 9 10 11 a Catalyst PdCl2 PdCl2 Pd(OAc)2 Pd(OAc)2 PdCl2(TPPTS)2 PdCl2(TPPTS)2 Pd(OAc)2 (TPPTS)2 Pd(OAc)2 (TPPTS)2 PdCl2(DPPF)2e Pd/C Pd/C Base Et3N Na2CO3 Et3N Na2CO3 Et3N Na2CO3 Et3N Na2CO3 Na2CO3 Et3N Na2CO3 Time (h) 4 4 4 4 4 4 4 4 4 4 4 Yield (%) Heckb 74 100 65 72 87 100 (83)d 56 100 86 40 78 Time (h) 1 1 1 1 1 1 1 1 1 1 1 Yield (%) Suzukic 76 90 81 95 83 94 66 75 82 61 88 0. 0. The use of palladium salts and complexes as catalysts and inorganic bases as co-catalysts yielded more products (Table 4). and the reactions were re-run under identical conditions. 44]. as the formation of palladium aggregates was observed. [40]). [44]). b 4 h. 80 °C.194 Adi Wolfson.01 mmol catalyst. Table 5. . equal amounts of fresh substrates and sodium carbonate were added to the glycerol. d Styrene was employed instead of butyl acrylate. Various halobenzenes can be employed and as expected.1'-Bis (diphenylphosphino) ferrocene) and the supported palladium catalyst (Pd/C) in glycerol was examined in the Suzuki cross-coupling of iodobenzene and phenylboronic acid (Figure 3b. A more intense study of the scope and limitations of C-C coupling in glycerol was reported later for both the Heck coupling of halobenzenes with various alkenes and the Suzuki cross-coupling of halobenzenes with phenylboronic acid (Figure 3a and b. iodobenzene was the most active halobenzene. In general.75 mmol butyl acrylate or phenylboronic acid. 0.5 mmol iodobenzene. Christina Dlugy and Dorith Tavor catalytic reaction in glycerol was the palladium-catalyzed Heck C-C coupling reaction of iodobenzene and butyl acrylate (Figure 3a. Table 4. The activity of PdCl2(DPPF)2 was not reduced after each cycle while those of PdCl2(TPPTS)2 and Pd/C were (Table 5).6 mmol base. The recycling of transition metal complexes of the types PdCl2(TPPTS)2 and PdCl2(DPPF)2 (DPPF= [1. 0. In the case of PdCl2(TPPTS)2. Then. eAs above. glycerol also enabled both solvent and catalysts to be recycled [40. As a sustainable solvent. 5 g glycerol. Catalysts were recycled after the extraction of both iodobenzene and biaryl from the glycerol catalytic phase using diethyl ether. it was found that glycerol can function as an alternative green solvent for the C-C coupling reactions. the authors assumed that the reduction in its activity may have resulted from the decomposition of the complex. 1h. glycerol synthesis via alcoholysis yielded crude glycerol with alcohol. or methyl esters of fatty acids were added to the pure glycerol during the reaction. The reaction was compared to those in pure glycerol and in pure glycerol with the addition of methanol and water to resemble crude glycerol contaminates (Table 4).8 47. 2 mol% palladium.6 mmol butyl acrylate. It was found that while the addition of either methanol or water did not affect reaction conversions.6 mmol Na2CO3. 0. Table 5. b 20 g glycerol. The authors mentioned that since .2 86. 0. as in the case of PdCl2(TPPTS)2.5 77.2 71. entry 3). b Addition of 0. crude glycerol from several oil sources and without any purification was also tested as a reaction medium in the palladium-catalyzed Heck coupling of iodobenzene and butyl acrylate using various catalysts (Figure 3a. The tedious purification process may be avoidable.0 Crude glycerol with the addition of KOHc 63. although it was found that the crude glycerol yields were lower than those in pure glycerol with all the catalysts tested. usually it must be in its highly refined and purified form. biodiesel.4 Reaction conditions: 5 mL glycerol. small amounts of methanol. Conversions of iodobenzene in the palladium-catalyzed Heck coupling of iodobenzene and butyl acrylate in crude glycerola [45] Entry Catalyst Pure glycerol Pure glycerol+ methanolb 96. and soap as leftovers. pure glycerol was mixed with methyl esters of fatty acid. however.8 85.5 mmol iodobenzene.3 76. d Before the reaction. water. entry 3). for more stable complexes. In general.6 mmol phenylboronic acid. the addition of fatty acid esters. To test whether leftovers from crude glycerol synthesis caused the reduced performance.1 86. Table 6.4 39. 80 °C.6 Pure glycerol+ waterb 97.6 45.25 g methanol or water.2 70.Glycerol as a Sustainable Solvent for Homogeneous Catalysis 195 As previously mentioned.e. 80 °C.8 1 2 3 4 a PdCl2 Pd(OAc)2 PdCl2(TPPT S)2 Pd/C 94. c Addition of 0. In addition. [44]). crude glycerol is used as the reaction medium. if non-purified. 0. 0. Therefore.1 (73)d 75. i.5 41.9 77. Catalyst recycling in the Suzuki cross-coupling of iodobenzene and phenylboronic acid in glycerola [44] Yield (%) Pd/C 98 61 50 Catalyst /Cycle 1 2 3 PdCl2(TPPTS)2 88 55 47 PdCl2(DPPF)2b 82 80 80 a 0.7 78. they were still satisfactory.5 mmol KOH. water. the conversion in crude glycerol was close to that of the reaction in pure glycerol (Table 6. 4 h.5 mmol iodobenzene.1 70. to pure glycerol resulted in a lower conversion (Table 6. Yet when glycerol is used as a reactant or as an additive. Table 6.2 Crude glycerol without the addition of KOH 58. 5 g glycerol. entry 11. Nevertheless. the glycerol and the soluble base within were also successfully recycled by extraction of the product with diethyl ether and the addition of fresh substrate. using fresh or residual KOH from alcoholysis as a catalyst. and comparable yields were produced during each subsequent synthesis. O 2 KOH 800C. probably since some of the KOH was lost and deteriorated during the alcoholysis of the oil. Similar conversions with both reactions. Another example of a recyclable catalytic system involving glycerol entails the use of CeCl3*7H2O in indole reactions with aliphatic and aromatic aldehydes (Figure 5. Finally. it is possible that the biodiesel and the soap traces in the crude glycerol coordinated to the catalyst and decreased its activity.196 Adi Wolfson. aromatic + RCHO CeCl3*7H2O 750C. Table 2.5-10h X NH 70-95% yield NH X Figure 5. R 2 X NH X=H. Aldol condensation of n-valeraldehyde [45]. Table 2. Christina Dlugy and Dorith Tavor the palladium-catalyzed Heck coupling of halobenzene and activated olefin involved coordination of a double bond of an olefin to the catalyst. . [45]). 1. 2h H O H H Conversion with the addition of KOH: 43% Conversion without the addition of KOH: 28% Figure 4. entry 12. it was found that the oil source did not affect reaction performances [45]. Synthesis of bis(indolyl)methanes [46]. As expected. In addition. A variety of bis(indolyl)methanes were synthesized in good to excellent yields and the glycerol and catalyst mixture was re-used up to five times after extraction of the product with ethyl acetate without special treatment. the condensation occurred with or without the addition of excess base. as crude glycerol was produced by the alcoholysis of triglyceride in the presence of KOH—which can also serve as co-catalyst in Heck coupling—the reaction was run with and without the addition of extra KOH. [46]). The reactions run without the extra addition of fresh KOH yielded lower conversions. Br R=Aliphatic. Crude glycerol from several oil sources was also used as a reaction medium in the aldol condensation of n-valeraldehyde (Figure 4. revealing that the residual base from the synthesis of crude glycerol can be re-used in the Heck reaction (Table 6). resulting in mass transfer limitations and lower activity. Employing a new family of aminopolysaccharides (APs) as surfactants and catalysts with basic characters led to a decrease in reaction time and yielded only trace amounts of byproduct from the epoxide-glycerol reaction. 3h Conversion without the addition of surfactant: 61% Conversion with the addition of surfactant: 84% Figure 6. The addition of surfactant to the reaction mixture can facilitate the mixing of the two phases to produce an emulsion-like system. The catalytic hydrogenation of styrene (which has a low solubility in glycerol) using a RhCl2(TPPTS)3 catalyst was studied in glycerol with and without the addition of surfactant (Figure 6. but the addition of Pluronic. [40]). [47]) in their study of the base-catalyzed ring opening reaction of epoxides (Figure 7). yielding full epoxide conversion after only 18 h and large amounts of by-product from the epoxide-glycerol reaction. Initially. which have long hydrocarbon chains. + Rh(TPPTS) 3 Cl2 H2 80 0 C. The authors assumed that the low activity was due to the low solubility of the reactants. Catalytic hydrogenation of styrene [40].Glycerol as a Sustainable Solvent for Homogeneous Catalysis 197 Emulsion Catalytic Systems in Glycerol The high polarity of glycerol enabled the products to be easily isolated and the catalyst to be easily recycled by extraction with hydrophobic organic solvents like ethers and esters. in which case biphasic systems may develop. . entry 17. a triblock copolymer surfactant. several conventional solid bases were employed as catalysts. in the polar glycerol catalytic phase. increased the conversion by almost 40%. Table 2. The reaction without added surfactant was slower then that in methanol under similar conditions. Karam and co-authors also demonstrated a noteworthy emulsion catalytic system in glycerol (Table 2. entry 13. from 61% to 84%. (Figure 7). Yet the polarity of glycerol may also be a drawback when the reactants comprise highly hydrophobic compounds. but also in other base-catalyzed reactions in glycerol. rapid phase separation at the end of the reaction allowed easy product extraction without the assistance of organic solvents. the highly glycerol miscible reaction products are difficult to extract using glycerol immiscible solvents. selectivity (ester/ether)=80/15 Aminopolysaccharide (AP): time=3 h. [48]). . The procedure was successfully used not only in the selective ring opening of epoxides with carboxylic acids. Ring opening of epoxides [47]. The same sugar-based surfactants (APs) were also used to stabilize palladium nanoparticles in the β. the β. However. was tested as an extraction solvent. As a result. Christina Dlugy and Dorith Tavor OH O ( )9 ( )9 O ( )9 O ( )9 + O Product ester OH ( )9 O OH OH Glycerol ether Solid base : time=18 h. The authors suggested that the use of APs allowed the organic substrates to diffuse better in the glycerol phase by creating hydrophobic environments within the glycerol. 250 bar. β-diarylation of acrylates [48]. scCO2. NH3 Ar Ar O OR 2 Ar-I 1200C 70-90% Yield Figure 8. the β. β. β-diarylation of acrylates (Figure 8. Table 2. Moreover. Furthermore. which was found to be soluble in glycerol (glycerol is only negligibly soluble in scCO2). selectivity (ester/ether)=95/traces Figure 7. and with a scCO2 flow of 40 g min−1. Henry reactions. O OR + Pd/AP. distillation of the glycerol is also not a feasible option due to its high boiling point.198 Adi Wolfson. β-diarylated products were cleanly and selectively recovered with a molar purity of 93% while the Pd/AP remained in the glycerol phase. conversion=98%. such as Knoevenageltype reactions. It was found that at 50 °C. conversion=98%. Hence. they found that micellar catalysis in glycerol was superior to that in water as the emulsions formed in glycerol were found to be unstable. β-diarylation of acrylates is performed at high temperatures in organic solvents with high boiling points. and Michael additions [47]. entry 15. Typically. but a greener synthesis route is possible with glycerol because of its greater environmental friendliness and because the reaction temperature can be reduced when using glycerol [48]. which was carried out in a domestic microwave at lower temperatures than under conventional heating. for which the glycerol functioned as both solvent and resolving agent (Table 2. glycerol is also applicable in microwavepromoted reactions. Table 2. Glycerol as Reactant and Solvent In the above-mentioned reactions. glycerol can also function as a reactant. yielded large amounts of waste that had . the Suzuki C-C cross coupling reaction in glycerol was also performed under microwave irradiation in a domestic microwave (Table 7). especially those with hydroxyl substitution are very attractive solvents for this purpose due to their high dielectric constants and high boiling points. glycerol was used as a sustainable solvent. NH2 H O + N H2NNH2 + KOH Yield=100% Selectivity=100% Figure 9. The reaction. Hence. [50. Microwave-promoted Wolff-Kishner reduction of benzaldehyde to toluene in glycerol [43]. highly polar organic solvent. [43]). Based on the ability of the solvent to absorb microwave energy and convert it into heat. 49]). glycerol seems to be an excellent candidate for microwave-assisted reactions. In another example. 51]). entry 16. microwave heating is a more efficient and energy saving alternative to conventional heating [56. previously studied in the presence of metal hydrides as stoichiometric reductants (Table 2. Table 2. 57]. facilitated easy separation of the products and recycling of the catalysts. non-volatile up to very high temperatures. The reduction of unsaturated compounds in glycerol. 43]). In addition to being a solvent. and supported more efficient heating. [40. entry 2. Polar solvents. where it enabled the dissolution of both reactants and catalysts. [40. The results illustrated in Table 7 confirmed the assumption that glycerol can be used successfully as a solvent in microwave-assisted reactions. entry 7. glycerol was used simultaneously as solvent and hydrogen donor in the catalytic transfer-hydrogenation of various unsaturated organic compounds while oxidizing to dihydroxyacetone (Figure 10. enhanced reaction activities and selectivities. One example of such a system is the lipase catalyzed kinetic resolution of an ester racemate in glycerol. microwave-promoted heating was also reported to enhance C-C coupling reactions [58]. glycerol is superior to water and other organic solvents typically used for this purpose. and it yielded full conversion and selectivity to toluene. In addition. Therefore. In addition. The first example of a microwave promoted organic transformation in glycerol was the Wolff-Kishner reduction of benzaldehyde to toluene (Figure 9.Glycerol as a Sustainable Solvent for Homogeneous Catalysis 199 Microwave-assisted Synthesis in Glycerol As a non-volatile. entry 22. was much faster. Table 7.200 Adi Wolfson.6 mmol phenylboronic acid. entry 18. 2 mol% palladium. [40. Alternatively. Microwave-promoted Suzuki cross-coupling of iodobenzene and phenylboronic acid in glycerola [44] Entry 1 2 3 a Heating oil bath microwave microwave Time (min) 60 5 10 Conversion (%) 94 15 61 Reaction conditions: 0. entry 17. the catalytic hydrogenation of several organic molecules (Table 2. 700C O + 3 HO + Yield=43% HO OH + 2 H2O Figure 10. This new catalytic system did not produce large amounts of waste as with the metal hydride. 43]) as well as the enantioselective hydrogenation of ethyl acetoacetate over RuBINAP in glycerol (Table 2. 5 g glycerol. NaOH 24 h. On the other hand. 700C O + HO + Yield=100% HO OH CHO OH c) CH2OH OH Raney Nickel.6 mmol Na2CO3. glycerol also enabled easy product separation and catalyst recycling. CHO OH a) CH2OH OH Ru(p-cumene)Cl2-dimer. and glycerol was dehydrogenated to dihydroxyacetone. 60]. Moreover. Transfer-hydrogenations of unsaturated organic compounds in glycerol [50]. and unlike hydrogenation with molecular hydrogen. KOH O + HO 24 h. thus making the reduction procedure less environmental friendly and less attractive. 4h. 0. using glycerol as the hydrogen source in a transfer-hydrogenation system resulted in very high product yields. 700C + Yield=99% HO OH CHO OH b) CH2OH OH Pd/C 5 h. as was previously shown. 80 °C. [43]) were limited most likely by the low solubility of molecular hydrogen in glycerol. neither special equipment nor precautions were necessary. . Christina Dlugy and Dorith Tavor to be neutralized. a valuable intermediate in the production of many chemicals [59. 0.5 mmol iodobenzene. [6] Sheldon. [2] Moulijn. the presence of glycerol as a solvent improved product yields and selectivities and enabled catalyst recycling. R. 1979.. A. Transition Metals for Organic Synthesis. In many reactions. [9] Beller. H. K. the effects of glycerol itself and of contaminants from its production process on reaction performance should also be explored further. In addition. [3] Mikami.. Glycerol was successfully used as a solvent in many catalytic and non-catalytic organic reactions. 189.. and Mass Transfer. Catal. 2005. 2001. H. van Bekkum. U. New York. [5] Christian. the low solubilities of gases such as hydrogen and oxygen in glycerol that limit its applications in catalytic hydrogenation and aerobic oxidation. and supercritical carbon dioxide. using homogeneous and heterogeneous chemo. [4] Nelso. These weaknesses should be further studied with the aim to provide novel solutions. Green Solvents for Chemistry: Perspectives and Practice. A. Blackwell. glycerol can dissolve many organic and inorganic compounds and transition metal complexes while also allowing easy product separation by extraction with glycerol immiscible solvents such as ethers. W. J. Downing. hydrophobic organic solvents for product extraction and catalyst recycling. R. 163-183. S. Catal. there are several drawbacks to its utilization. non-hazardous. Furthermore. glycerol can be used as a solvent without purification. Weinheim. Wicks. Studer. REFERENCES [1] Welty. Wiley-VCH. John Wiley. M. [10] Gerhartz. Fundamentals of Momentum. John Wiley. Fine Chemicals through Heterogeneous Catalysis. 191-204. [8] Sheldon. Verlag Chemie. E.e. A. Oxford University Press. C. Green Reaction Media in Organic Synthesis . . A 1999. Appl. including the low solubility of highly hydrophobic compounds in glycerol. W.. recyclable. 1990. and the use of hazardous. In addition. R. and microwave promoted reactions. and biodegradable. 1998. R. and biological properties that make it non-volatile. A 1999. R. esters. Wiley-VCH.. Appl. such as in the catalytic transfer-hydrogenation of various unsaturated organic compounds and in the transesterification of alcohols. Finally. 189. E. Bolm. 2004. R. Weinheim. Heat. 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N.. . benzyl. and ketones prepared in this way are important intermediates in the manufacture of dyes. Parekh Marg. Mumbai-400 019. phenoxycarbonylation. aminocarbonylation. India. Email address: .: +91 22 33612601. Patil and Bhalchandra M. Matunga. esters. and other industrial products. thiocarbonylation.in. thioamides etc. The term carbonylation covers a large number of closely related reactions that all have in common that carbon monoxide is incorporated into a substrate by the addition of CO to an aryl-. have been explored using palladium as a catalyst of choice. such that nowadays plethora of palladium catalysts and various synthetic protocols are available for the synthesis of aliphatic and aromatic carboxylic acids as well as their derivatives. 22 33611020. Chapter 7 HOMOGENEOUS CATALYSIS IN CARBONYLATIVE COUPLING REACTIONS Pawan J. Yogesh P.In: Homogeneous Catalysts Editor: Andrew C. Tambade. Palladium-catalyzed carbonylation reactions of alkenes/alkynes. Palladium along with variety of ligands has been widely employed as homogeneous catalysts to affect carbonylation reactions. carbonylative Suzuki coupling reaction.bhanage@ictmumbai. bm. pharmaceuticals. N. Poehler ISBN: 978-1-61122-894-6 © 2011 Nova Science Publishers. * Corresponding author: Tel. which reveals that complex synthetic processes can be accomplished under carbonylation conditions.com.or vinylpalladium complex in presence of suitable nucleophiles. fax: +91 bhalchandra_bhnaage@yahoo. aromatic halides with different nucleophiles have undergone rapid development since the pioneering work of Reppe and Heck. Bhanage* Department of Chemistry. Various carbonylation reactions like alkoxycarbonylation.edu. Inc. Institute of Chemical Technology. The carboxylic acid and its derivatives like amides. ABSTRACT Carbon monoxide is a ubiquitous molecule in organometallic chemistry and an important feedstock in multiple catalytic processes both at the laboratory and industrial levels. carbonylative Sonogashira coupling reaction etc. The scope of carbonylation reactions is also extended for the synthesis of pharmaceuticals and their important intermediates using carbonylation as the key step using homogeneous catalysis. agrochemicals. carbonylation represents industrial core technologies for converting various bulk chemicals into a diverse set of useful products of our daily life.206 Pawan J. by carbonylation gives access to more valuable products such as aldehydes. esters. Yogesh P. amines (aminocarbonylation). The term carbonylation was coined by W. Patil and Bhalchandra M.or vinylpalladium complex in the presence of various nucleophiles (Scheme 1). the basic raw materials for the chemical industry. Typically. the leaving group X is formally replaced by the nucleophile with incorporation of carbon monoxide molecule (Figure 1). In general. Bhanage Herein. whereby. forming the basis for industrial and laboratory processes currently in practice [1-4]. alkyne (carbonylative Sonogashira). amides. INTRODUCTION The development of environmentally benign and efficient synthetic methods continues to be a central goal of current research in chemistry. Tambade. we summarize the recent developments in homogeneous catalysts and selected organic applications in this area. Hence. aromatic halides are treated with an appropriate nucleophile in a carbon monoxide atmosphere in the presence of a catalytic amount of a palladium complex. alcohols and carboxylic acid derivatives. These processes are employed worldwide to prepare millions of tones of commodity chemicals each year. whereby. Prime examples for such transformations are carbonylation processes. the leaving group X is formally replaced by the nucleophile with incorporation of carbon monoxide molecule. Transition metal-catalyzed carbonylation of aryl halides in the presence of nucleophiles is an important methodology for the preparation of aromatic carbonyl compounds which includes ketones. Noteworthy among the commercial carbonylation processes are the ‘oxo’ process (olefin hydroformylation) [5-7]. In general. boronic acid (carbonylative . Some of the initial scientific discoveries in this field gradually evolved into large-scale commercial carbonylation processes. Reppe during the thirties and is generally used to refer to those reactions in which CO alone or CO combined with other compounds (especially nucleophiles with mobile H-atoms) are introduced into particular substrates (Saturated or unsaturated). Among the different catalytic reactions. Carbonylation reactions rank among the most useful transformations homogeneously catalyzed by transition metal complexes. acids and their derivatives [1-4]. The term carbonylation covers a large number of closely related reactions that all have in common that carbon monoxide is incorporated into a substrate by the addition of CO to an aryl-. In this regard. which make use of carbon monoxide currently the most important C1 building block. the Reppe process (hydroxycarbonylation of acetylene to acrylic acid) and Monsanto process (carbonylation of methanol to acetic acid) [8] etc. the conversion of olefins. alcohols (alkoxycarbonylation). aromatic halides are treated with an appropriate nucleophile in a carbon monoxide atmosphere in the presence of a catalytic amount of a palladium complex. the reactions require a stoichiometric amount of base to regenerate the catalyst. benzyl. Which of these products is obtained depends on the nucleophile: water (hydroxycarbonylation). the refinement of readily available feedstock to more-functionalized products is of particular importance. catalysis and organometallic chemistry are key techniques for achieving these objectives and for contributing to a “greener” chemistry in the future. For example. I. OTf. A variety of carbonylation products can be prepared from the same aromatic substrate simply by changing the nucleophile. O O O R NRR' R R-NHR' R OH OR R-X R- O H R- X RO H2 X O R R R R-X CO ' HR R-X O R-SH R- R SR N R- X B R- R-X )2 H (O O RSnBu3 NRR' O R O R'RN R R R Figure 1. the use of carbon monoxide as a carbonyl source for aldehydes.. O X Palladium Nu R + CO + Nu H R Base X = Cl. N2Nu = OH.. NR2R3 . Br. . can be used. ketones. Pd-catalyzed carbonylation reactions.. carboxylic acids and their derivatives in various transition metal-catalyzed reactions has become probably the most widespread methodology for homogeneous catalytic reactions.Homogeneous Catalysis in Carbonylative Coupling Reactions 207 Suzuki) etc.. Scheme 1... an advantage with respect to biologically active compound libraries. OR1. Pd-catalyzed carbonylation of aryl halides. Nowadays. Cotoin. CARBONYLATIVE SUZUKI COUPLING REACTION Diarylketones constitute an interesting and versatile structural motif which is frequently present in natural products (e. i) oxidative addition of aryl halide to palladium to form aryl palladium halide complex. ii) insertion of carbon monoxide into aryl palladium halide complex to form acyl palladium halide intermediate. Some of important contributions in this area are summarized below. Among the various carbonylation reactions. It has been observed that mostly homogeneous transition metal catalysts are reported for carbonylative coupling reactions as they provide product in higher yield at ambient conditions. iii) reductive elimination to yield the product. Tambade. Bhanage The suggested mechanism for carbonylation reactions of aryl halide is shown in Figure 2. Initially there is oxidative addition of aryl halide to palladium which forms aryl palladium halide complex (intermediate II). Yogesh P. L Oxidative addition R Pd L II I CO CO insertion L RI PdLn I Base HI H R C O Pd L III I L Pd L I NuH Reductive elimination R C O Nu Figure 2. In the catalytic cycle base plays a crucial role to generate a active palladium species which then continues the catalytic cycle. Coordination and migratory insertion of CO then forms acyl palladium halide complex (intermediate III). Patil and Bhalchandra M. General mechanism for Pd-catalyzed carbonylation of aryl halide. The intermediate III is then attacked by nucleophile and undergo reductive elimination to give carbonylated product. carbonylative coupling reactions has gained considerable attention in recent years and several catalytic systems has been developed to affect theses transformations. Papaveraldine).g.208 Pawan J. in non-steroidal anti-inflammatory . The key steps in the mechanism of carbonylation reactions are. I. In 1993. Here. air and moisture stable. They used PdCl2(PPh3)2 as catalysts for this transformation. O N OMe OMe OMe OMe OMe SO3H OMe O OH O OH Papaveraldine Sulisobenzone Oxybenzone O OH O S COOH O COOH HO OMe Cotoin Suprofen Ketoprofen Figure 3. Oxybenzone) (Figure 3). . OTf. the coupling reaction of organoaluminium [16] or organosilane [17] compounds with electron-poor aryl halides is severely limited due to the formation of biaryl side products. palladium-catalyzed coupling of boronic acids with carboxylic anhydride [13] or nickel-catalyzed coupling reactions of aryl iodides with aromatic aldehydes [14]. N2+) derivatives. K2CO3 was found to give good yield of carbonylated products. Typically. Sulisobenzone. introduced the coupling of aryl boronic acids with aryl iodides for the synthesis of diarylketones (Suzuki carbonylation) (Scheme 2) [18]. Unfortunately. Suzuki et al. An especially versatile approach for the synthesis of diarylketones [15] is the transitionmetal-catalyzed three-component cross-coupling of Aryl-X (X = Br. this reaction requires overstoichiometric amounts of Lewis acid and the regioselectivity is often limited to the paraposition. Suprofen.g. Ketoprofen) and occurs in UV screens (e. Thoroughly they have investigated effect of base on selectivity of the reaction. In principle. diaryl-ketones are prepared by Friedel–Crafts acylation of ortho/para-directing arenes with acyl halides [9].g. aryl halide and aryl boronic acid. Other synthetic strategies use cross-coupling reactions of benzoic halides with organotin compounds [10-12]. Palladium catalyzed carbonylative Suzuki coupling reaction is one of the most promising method for direct synthesis of biaryl ketones from carbon monoxide. electron-withdrawing groups on the aryl ring accelerate the rate of transmetallation to form the Ar–Pd–Ar intermediate and hinder the insertion of carbon monoxide into the Ar–Pd–X species. Applications of Carbonylative Suzuki coupling reaction. However. carbon monoxide and aryl metal reagents.Homogeneous Catalysis in Carbonylative Coupling Reactions 209 drugs (e. these reactions provide a versatile tool for diarylketones synthesis as boronic acids are generally nontoxic and thermally. The catalyst was applicable for various halopyridines providing moderate to excellent yield of the desired products. Palladium(II) acetate and N. Castanet et al. They developed a high yielding protocol for the synthesis of α-pyridyl ketone using PdCl2 (PCy3)2 as a catalysts of choice. PdCl2/dppf Base Z Y Z O C B(OH)2 + CO + X Y Scheme 3. Further application of carbonylative Suzuki coupling reaction for the synthesis of pyridylketones was explored by Castanet and group (Scheme 5) [21]. PdCl2/dppf catalyzed carbonylative Suzuki reaction. PhB(OH)2. Pd(OAc)2/imidazolium salt catalyzed carbonylative Suzuki reaction of halopyridines.Imidazolium salt CO. The reaction was optimized with respect to various parameters such as time. Patil and Bhalchandra M.N-bis-(2. X N Pd (OAc)2 . reported a simple and efficient method for the syntesis of α-pyridyl ketone from chloropyridines using Pd(OAc)2/imidazolium salt as a catalyst (Scheme 4) [20]. Base N COPh Scheme 4.6-diisopropylphenyl)dihydroimidazolium chloride (2 mol%) was used to catalyze the carbonylative coupling of aryl diazonium tetrafluoroborate salts and aryl boronic acids to form aryl ketones by Song et al. temperature.210 Pawan J. (Scheme 6) [22]. Bhanage Ar-B(OH)2 + CO + I-Ar ' PdCl2(PPh3)2 Base Ar-CO-Ar ' Scheme 2. The catalyst system was applicable for variety of aryl diazonium tetrafluoroborate salts and aryl boronic acids. . aryl bromide and aryl triflates. Palladium catalyzed Suzuki carbonylation reaction. Later on in 1998 they have developed PdCl2/dppf as a versatile catalyst for the same reaction (Scheme 3) [19]. Tambade. Yogesh P. Various pyridine-chlorides were carbonylated with phenyl boronic acid to yield the desired product in moderate to good yields (51-86 %). CO pressure and solvent. Furthermore they have proposed a possible reaction mechanism. The catalyst was applicable for large variety of aryl electrophiles such as aryl iodide. Carbonylative Suzuki coupling reaction 1-iodo-cyclohexene and phenylboronic acid (or 3-trifluoromethoxy-phenylboronic acid) was carried out using Pd(PPh3)4 complex by Kollar and group (Scheme 7) [23]. i-Pr Cl N I-Pr i-Pr - i-Pr Ph-N2+ BF4 + (OH)2B-Ph - Pd (OAc)2 . PdCl2 (PCy3)2 catalyzed carbonylative Suzuki reaction of halopyridines. The catalyst shows excellent activity for less reactive substrate i. The active catalyst Pd(0) is generated in-situ by the reaction of Pd(OAc)2 and PPh3. Carbonylative coupling of aryl diazonium tetrafluoroborate salts and aryl boronic acids.e. O Ph Ph CO Scheme 6. . however. substantial amount of byproduct was also forming in the reaction.Homogeneous Catalysis in Carbonylative Coupling Reactions 211 Scheme 5. 1iodo-cyclohexene providing good to excellent yield of the desired product. O Ph S Br + ArB(OH)2 CO (1 atm). Palladium-catalyzed three-component Suzuki cross-coupling reaction Beller et al. This method does not require an overpressure of carbon monoxide or special ligands. Tambade. Patil and Bhalchandra M. Carbonylative Suzuki coupling of 1-iodo-cyclohexene. CsF Pd (PPh3)4 Ph O S O Ar Scheme 8. The carbonylative cross-coupling reaction is strongly favored over competing direct crosscoupling and homo-coupling processes. This reaction offers efficient access to various biologically active compounds as shown by the two-step preparation of Suprofen. Pd/L catalyzed carbonylative Suzuki coupling reaction. (Scheme 8) [24]. Yogesh P. The catalyst system was applicable for a broad range of aryl/heteroaryl bromides and aryl boronic acids at low catalyst loadings. except with boronic acids carrying strong electronwithdrawing substituents. carbon monoxide and aromatic boronic acids catalyzed by Pd(PPh3)4 has been developed by Asensio et al. A new and efficient approach to the synthesis of α-ketosulfoxides by carbonylative Suzuki coupling reaction between α-bromo sulfoxide. Bhanage I Pd (PPh 3 )4 CO B(OH) 2 O Pd (PPh 3 ) 4 CO OCF 3 B(OH) 2 O OCF 3 Scheme 7. . The reaction takes place under very mild conditions and with high selectivity for a wide range of boronic acids. reported Pd(OAc)2 /di-1-adamantyl-n-butylphosphine (cata CXium A) as highly active catalyst in the three-component Suzuki carbonylation reaction (Scheme 9) [25].212 Pawan J. O Br + CO + B(OH)2 Pd (OAc)2 / L MeO MeO P L R = Scheme 9. The reaction was carried out at room temperature and furnishes 72% yield of corresponding α.β-acetylenic ketones (Scheme 12) [28]. reported carbonylative three-component coupling reaction of aryl iodides with terminal alkynes catalyzed by PdCl2(PPh3)2 using an ionic liquid. n = 1 or 2 B(OH)2 R + Pd(TMHD)2/Pd(OAc)2 O R I R1 CO X n I X n Scheme 10. The ease of preparation of complex. Depending upon the combination of aryl halide and alkyne. palladium bis (2. as the reaction medium. indefinite shelf life. [BMim]PF6. They have checked various ionic liquids.6.β-alkynyl ketone. S. low-viscosity ionic liquid such as [BMim]NTf2 was not . range of alkynyl ketones can be produced. CARBONYLATIVE SONOGASHIRA COUPLING REACTION The carbonylation reaction in which aryl halide reacts with carbon monoxide and alkyne (as a nucleophile) to give alkynyl ketone as a product is known as carbonylative Sonogashira coupling reaction.2. O Pd(TMHD)2 R R1 R = CH3. X + R H + CO O cat PdCl2(PPh3)2 aq NH3 (0. high solubility in organic solvents. Palladium catalyzed carbonylative Sonogashira reactions. R1 = CH3.6-tetramethyl-3. Br. Carbonylative Suzuki coupling reaction of aryl and heteroaryl iodide with phenylboronic acid. Br.5 M) room temp R Scheme 11. OCH3. No2.5heptanedionate) [Pd(TMHD)2] or Pd(OAc)2 as the catalyst (Scheme 10) [26]. stability towards air and compatibility with various hindered and functionalized aryl/heteroaryl iodides and arylboronic acids makes it an ideal complex for carbonylative Suzuki coupling reactions.Homogeneous Catalysis in Carbonylative Coupling Reactions 213 Bhanage and group reported the carbonylative Suzuki coupling reaction of aryl and heteroaryl iodides with variety of arylboronic acids catalyzed by a well defined and stable phosphine free palladium complex viz. Ryu et al. which resulted in good yields of α. OCH3. X = N. Mori and co-worker reported palladium catalyzed carbonylative Sonogashira coupling of terminal alkynes with aryl iodides under atmospheric pressure of carbon monoxide was accomplished by using aqueous ammonia as a base in THF with or without use of CuI (Scheme 11) [27]. while noncarbonylative coupling product is not obtained. . The microflow system resulted in superior selectivity and higher yields for carbonylative Sonogashira coupling reactions of aryl iodides compared to the conventional batch system. 120 C o O Ar Ph Scheme 14. Bhanage suitable for this reaction. since the background Sonogashira coupling reaction. Et3N. Palladium catalyzed carbonylative Sonogashira reactions using multiphase microflow system. also proceeded. PdCl2(P(OPh)3)2 mediated carbonylative Sonogashira reactions. With the aid of imidazolium ionic liquids. a competing reaction. [BMim]PF6 or [MoCT]PF6 (BMim = 1-butyl-3methyl imidazolium cation. Tambade. X + R + CO H O PdCl2 (P(OPh)3)2 [BMim] PF6 or [MoCT] PF6 R Scheme 13. Me N N Bu Ph3P Pd Cl Ar-I + CO + Ph Cl H [BMim]PF6.214 Pawan J. MoCT =1-methyl-3-octyl imidazolium cation) catalyst was recycled and used for four consecutive catalytic cycles retaining its high activity. Ziolkowski and group shows PdCl2(P(OPh)3)2 mediated carbonylative coupling of phenylacetylenes with aryl iodides in organic solvents and in ionic liquids (Scheme 13) [29]. Yogesh P. X + R H + CO O PdCl2(PPh3)2 [BMim] PF6 Ar Scheme 12. They have developed low pressure microflow system for palladium catalyzed multiphase carbonylation reactions in an ionic liquid. Patil and Bhalchandra M. The protocol was applicable for variety of substrates and moderate to good yields of desired ketones were obtained. also showed application of multiphase microflow system for palladium catalyzed carbonylative Sonogashira coupling reaction of aryl iodides with phenylacetylene (Scheme 14) [30]. Ryu et al. PdCl2(PPh3)2/[BMim]PF6 catalyzed carbonylative Sonogashira reactions. Ar I Fe + CO + Ar CH Palladium Cat. The reaction gave much better yields of aryl ferrocenylethynyl ketones. reported a two-step synthesis of ferrocenyl pyrazole and pyrimidine derivatives based on carbonylative Sonogashira coupling of iodoferrocene with alkynes (Scheme 16) [23]. respectively. Foldes et al. The catalytic system was applicable for large variety of aryl iodides providing moderate to excellent yield of the desired carbonyl products. Palladium catalyzed carbonylative Sonogashira reactions of ferrocenylethyne. Et3N Fe SDS. water.Homogeneous Catalysis in Carbonylative Coupling Reactions 215 Chen and group have developed carbonylative coupling reaction of aryl iodides with ferrocenylethyne catalyzed by PdCl2 using sodium dodecyl sulphonate (SDS) as surfactant and water as solvent (Scheme 15) [31]. 5-trisubstituted pyrazoles and 2. .4. 25 C o C C C Ar + CO + Ar-I Scheme 15. which proceeded for 6 h at room temperature under a balloon pressure of carbon monoxide using Et3N as base. Fe O N Fe N R' Ar Fe N N Ar NHR' Scheme 16. Pd catalyzed carbonylative Sonogashira reactions of iodo ferrocene. New ferrocenyl 1. β-alkynyl ketones with hydrazines and guanidinium salts. C CH Fe O PdCl2/PPh3.6-trisubstituted pyrimidines were obtained by the addition-cyclocondensation reaction of the α. 3. The products were obtained with moderate to excellent yields and were characterized with the aid of various spectroscopic tools. Patil and Bhalchandra M. 1-hexyne and 1octyne etc. whereas. base and substrate/catalyst ratio were studied. This is the first report in which a copper complex is used as a catalyst for carbonylative Sonogashira coupling reaction instead of palladium catalyst. (Scheme 17) [33]. reported a facile protocol for carbonylative Sonogashira coupling reaction of aliphatic and aromatic alkynes with iodoaryls using a preformed Cu(TMHD)2 complex (Scheme 18) [34]. various catalytic protocols such as CO pressure. catalyst identity. By using a two-step multi-catalysis. The non-cyclic common intermediate was selectively prepared using [PdCl2(dppp)] as catalyst.e. The origin of the selectivity toward the 5-or 6-membered ring compounds was explained through the respective role of the various catalytic species involved. O I + NH2 + CO [Pd].216 Pawan J. base. i. Bhanage et al. Tambade. Yogesh P. Bhanage A selective one-pot synthesis of carbonyl-containing N-heterocyclic compounds has been developed using a carbonylative Sonogashira/cyclisation sequence by Djakovitch et al. In order to get either indoxyl or 4-quinolone products selectively.e. The protocol was general in nature applicable for carbonylative Sonogashira coupling reaction of wide variety of aryl iodides with aromatic/aliphatic alkynes such as phenylacetylene. {[Pd]+HNEt2}. with a tandem catalysis. solvent N H or N H O NH2 Scheme 17. indoxyls were synthesized. whether they are organic or metallic. O I R H + CO Cu [TMHD]2 R Scheme 18. Preparation of heterocyclic scaffolds via Carbonylative Sonogashira/cyclisation path. 4-quinolones were obtained. Cu[TMHD]2 catalyzed carbonylative Sonogashira coupling reaction. . temperature. AMINOCARBONYLATION REACTIONS Among the carbonylative coupling reactions aminocarbonylation reactions are widely explored because of appearance of amide functionality in various important compounds. {[Pd]/PR3}. i. They also extend the application of this complex for the aminocarbonylation reaction.6. Me N N N HN N O H N Me N NH O Cl N H2N O C N Cl N H Imatinib (Gleevec) Boscalid Procainamide O O N N H C O Ph NH2 Cl HO N O NHPr F Mosapride CJ-15. heterocyclic and alkenyl halides with primary/secondary amines in presence of carbon monoxide [35-36]. since those amides which are hardly available in conventional synthetic methods can be synthesized from easily available starting materials. pharmaceuticals and agrochemicals. Advantages of this method include the broad availability of substrates and the high tolerance of palladium catalysts against a variety of functional groups. reported palladium catalyzed selective and useful method for direct synthesis of amides via coupling of aryl.Homogeneous Catalysis in Carbonylative Coupling Reactions 217 Transition-metal catalyzed three-component cross-coupling reaction between amine. Whittall and group explored Bedford-type palladacycle complex in combination with dppf for the alkoxycarbonylation reactions (Scheme 19) [42]. Heck et al. Examples of carbonyl product in pharmaceutical and material research. this route has become a useful tool for the preparation of substituted amides. They have been found in biologically important natural products.5-. aminocarbonylation of 4-. Amides/anilides are attractive targets in chemical synthesis because of their wide utility and occurrence in a number of interesting molecules. alcohols.161. For example. anticonvulsants [37-38]. They are also used extensively in the polymer chemistry [39-41]. Beller et al. Pfizer k-Opioid receptor antagonist Figure 4. or 7-bromoindole with arylethylpiperazines provides a direct one-step synthesis for CNS active amphetamine derivatives. Various indole carboxylic acid derivatives are accessible in excellent yield. Therefore. and . This palladium complex acted as highly active catalyst for both the reactions showing compatibility with wide variety of substrates. This is the first example for the carbonylation of unprotected bromoindoles with various nucleophiles involving cyclic and acyclic amines. carbon monoxide and organic halides is now considered as a useful tool for the amide/anilide synthesis (Aminocarbonylation). demonstrated the aminocarbonylation of unprotected indoles with different N and O-nucleophiles using Pd/dppf as a catalyst (Scheme 20) [43]. Amides are widely used as an antiepileptic drug. had shown the application of microfluidic device for the rapid synthesis of amides via aminocarbonylation reactions (Scheme 21) [44]. They showed the application of microstructured device for first time to perform a gas–liquid carbonylation reaction. Depending on the substituents. Pd/dppf catalyzed aminocarbonylation of bromoindoles. reported aminocarbonylation of 2-iodoaniline and derivatives using Pd(OAc)2/PPh3 as a catalytic system. CO O R N N N N H O Scheme 20. The yields were moderate to good in very short period of time. Kollar et al. Palladacycle catalyzed carbonylation reactions. amino acid methyl esters) as N-nucleophiles 2-ketocarboxamides were obtained as major products in aminocarbonylation reaction with double carbon monoxide insertion. In the presence of various primary and secondary amines (t-butylamine. H2O) N H Pd(PhCN)2Cl2 dppf. R2NH. two types of compounds were synthesised: having methyl or hydrogen in 4position 2-aryl-benzo[1. ROH. 2-Iodoaniline derivatives were used as bifunctional substrates in palladium-catalysed carbonylation (Scheme 22) [45]. . CO MeO O + N O N Br MeOH MeO O OMe Scheme 19. NEt3.218 Pawan J. cyano or nitro groups in the same position resulted in the formation of dibenzo[1. Tambade.12dione derivatives.3]oxazin-4-one derivatives have been formed. chloro. H N MeO O OMe Pd [1] / dppf. Yogesh P. bromo. Patil and Bhalchandra M. Bhanage Gee et al.5]-diazocine-6. NH Ar R Ar Br N H Nu NuH (RNH2. An efficient Pd(OAc)2/PPh3 catalyzed protocol for the aminocarbonylation of heteroaryl iodides was reported Kollar and group (Scheme 23) [46]. CO. NO2 etc. Aminocarbonylation of 2-iodo aniline. Scheme 22. 3-iodopyridine and iodopyrazine. HNRR' N I O Pd(OAc)2 / PPh3 N O NRR' + N O NRR' O I N O NRR'' NRR'' CO. HNRR'' Pd(OAc)2 / PPh3 N + N O Scheme 23. including amino acid methyl esters. Cl. CN. 1iodo-2-methyl-cyclohexene and α-iodostyrene) with diethyl α-aminobenzyl-phosphonate as .Homogeneous Catalysis in Carbonylative Coupling Reactions 219 X + R NH2 CO Pd-phosphine catalyst O N H R Scheme 21. The reaction works well with electron-rich and electron-poor substrates on nucleophile. were used as nucleophiles in palladium-catalysed aminocarbonylation of 2-iodopyridine. CH3. The palladium-catalyzed aminocarbonylation of iodoalkenes (1-iodo-cyclohexene. The application of aminocarbonylation for the synthesis of novel N-acyl phosphonates with unprecedented structure was carried out by Kollar and group under mild and homogeneous reaction conditions (Scheme 24) [47]. Br. Pd/phosphine catalyzed aminocarbonylation reaction. 1-iodo-4-tert-butyl-cyclohexene. Pd(OAc)2/PPh3 catalyzed aminocarbonylation of heteroaryl iodides. R NH2 N R O O NH2 CO Pd (OAc)2 / PPh3 R I CO Pd (OAc)2 / PPh3 HN O R R O NH R = H. Various primary and secondary amines. 1° and 2° benzamides and methyl esters from the corresponding aryl bromides at atmospheric pressure of CO. Further.8-di-iodo-naphthalene. (Xantphos)Pd(Br)benzoyl. CO. The high chemoselectivity.220 Pawan J. Patil and Bhalchandra M. aminocarbonylation of 1. Bhanage N-nucleophile resulted in the exclusive formation of carboxamides. depending on the amine to substrate ratio. In addition.8-diiodo-naphthalene with various primary and secondary amines in the presence of palladium(0) complexes formed in situ from palladium(II) acetate and triphenylphosphine was reported by Kollar and co-workers (Scheme 25) [48]. Aminocarbonylation of 1. Aminocarbonylation of α-aminobenzyl-phosphonate. respectively. the easy work-up of the reaction mixtures. Yogesh P. The reaction tolerates structural variation of the iodo-substrate. Tambade. The same reaction with iodoaromatics (iodobenzene. as well as the high functional group tolerance at the N-alkyl substituent and at the aryl moieties. The method is effective for the direct synthesis of Weinreb amides. and an X-ray crystal structure was also showed. The reaction tolerates the ester functionality. H2NR Pd (OAc)2 / PPh3 I I O N R O Scheme 25. The highly selective formation of carboxamides to ketocarboxamides can be explained by favored single carbon monoxide insertion relative to double CO insertion. H 2N H P (O) (OEt)2 O I H H N P (O) (OEt)2 + CO Pd (OAc)2 /PPh3 Scheme 24. make these reactions of synthetic importance. respectively. The high chemoselectivity and the easy work-up of the reaction mixtures make these reactions of synthetic importance. A method for the aminocarbonylation of aryl bromide using xantphos as a ligand has been reported recently by Buchwald and group (Scheme 26) [49]. This crystal structure revealed . so that amino acid esters could serve as Nnucleophiles and in this way. two types of products have been obtained in highly chemoselective mode: dicarboxamides and Nsubstituted imides have been formed at high and low amine to substrate ratio. was synthesized. The catalytic system was applicable for variety of substrates providing good to excellent yield of desired carbonylated products. naphthalimides possessing stereogenic centre in the Nsubstituent could be synthesised. 2-iodothiophene) provided the corresponding carboxamide in high yields and some 2-keto-carboxamides as side products due to single and double carbon monoxide insertion. In the case of primary amines. a putative catalytic intermediate. in contrast to the majority of Pd-aryl complexes ligated by Xantphos. NO2 R2/R3 = H. . Bhanage and co-workers reported the facile protocol for aminocarbonylation of aryl iodides with aromatic/aliphatic amines catalyzed by phosphine-free palladium catalysts in environmentally benign water as a solvent (Scheme 27) [50]. CH3.Homogeneous Catalysis in Carbonylative Coupling Reactions 221 that this species possesses. Excellent yields of desired amides were obtained by using only 0. Pd(OAc)2 catalyzed aminocarbonylation reactions. 8 h R O NR2R3 R = H. 1atm CO 2-3 % Pd(OAc)2 2-6 % Xantphos R Nuc NucH = HN(OMe)Me. O Br R NucH. alkyl or aryl Scheme 27. X R + R2 N H R3 CO. The protocol is applicable for carbonylative coupling reactions of various electron rich.5 mol% of the catalyst under optimized reaction conditions. Water. HNR2. Pd (OAc)2 Et3N. N Br NaBH4 NH Br Pd (OAc)2 / PPh3 CO. Synthesis of protoberberine alkaloid using carbonylation reaction. Pd(OAc)2 /Xantphos catalyzed aminocarbonylation reaction. OCH3. a cis-coordinated palladium center. electron deficient and sterically hindered aryl iodides with different amines affording excellent yield of desired products. K2CO3 N O LiAlH4 N Scheme 28. MeOH Scheme 26. by treating with excess LiAlH4. Carbonylation of 1-(20-bromo-30. ALKOXYCARBONYLATION AND HYDROXYCARBONYLATION REACTIONS The carbonylation reaction in which aryl halide reacts with carbon monoxide and phenol/alcohol (nucleophile) to give esters as a product is called as alkoxycarbonylation reaction. 40-dialkoxybenzyl)tetrahydroisoquinolines by treatment with CO (1 atm) in the presence of Pd(OAc)2. Bessard et al. Bhanage Orito et al. Alkoxycarbonylation of aryl chlorides 1. DMF or DMSO. the Bischler–Napieralski cyclization products reduced to corresponding 1-(20-bromo-30. 40-dialkoxybenzyl). these lactams were converted almost quantitatively into protoberberine alkaloids.2 equiv PhOH 2 mol % Pd (OAc)2 4 mol % dcpp 2HBF4 1. PPh3 and excess K2CO3 in boiling toluene gives 8-oxoberbines in good yields. They have shown the coupling of different aryl chlorides with variety of aliphatic alcohols which provides product in moderate to good yields (Scheme 29) [52]. reported a facile protocol for the alkoxycarbonylation of aryl chlorides using palladium acetate in combination with phosphine containing ligands. CO (1 atm) 4Ao MS. 100-120 oC. CO Cl P P COOR R' ROH Pd(OAc)2 R' Scheme 29.HBF4 catalyzed alkoxycarbonylation reaction. Depending upon the phenol/alcohol employed one can get variety of aromatic or aliphatic esters. Patil and Bhalchandra M.222 Pawan J.tetrahydroisoquinolines using NaBH4 as a reagent of choice. Yogesh P. 6-24 h O OPh Cl R R Scheme 30. . Further. Tambade. described preparation of protoberberine alkaloids which involves carbonylation as one of the major step during synthesis (Scheme 28) [51].5 equiv K2CO3. Dihydroisoquinolines. Pd(dcpp)2. The palladium-catalyzed carbonylation of aryl halide with carbon monoxide and water is referred to as hydroxycarbonylation reaction. The catalyst systems were optimized with respect to various parameters and enabled carbonylation of electron-rich. reported an efficient protocol for the alkoxycarbonylation reaction of aryl iodide with alchohol and phenol as a nucleophile (Scheme 32) [55]. with different types of phenols and alcohols affording excellent yields of the desired products. Various functional groups were tolerated and the yields were from moderate to excellent. A Base. Pd(TMHD)2 catalyzed alkoxycarbonylation reaction. functional group tolerant method of the preparation of phenyl acids and esters from aryl chlorides via palladium-catalyzed carbonylation reactions using atmospheric pressure of carbon monoxide (Scheme 33) [53]. R Nu Scheme 32. CO(Ballon). O I R Pd (TMHD)2 CO. They employed Pd(TMHD)2 as a phosphine-free homogeneous catalysts. Depending upon the aryl halide used variety of aromatic acids can be obtained.HBF4 as a efficient catalyst (Scheme 30) [53]. H-Nu. EtOH. They employed Pd(OAc)2/ . Buchwald et al. Bhanage et al. I PdCl2(CH3CN)2. The catalyst is further employed for the synthesis of various acid derivatives via carbonylation reactions. Palladium/thiourea-oxazoline catalyzed alkoxycarbonylation reaction. electron-deficient and sterically hindered aryl iodides. The catalyst was successfully used for aryl and heteroaryl chlorides in combination with variety of a aliphatic and aromatic alcohols. It allows the straightforward and atom-efficient preparation of aromatic carboxylic acids. reported carbonylation of aryl chlorides at ambient CO pressure using Pd(dcpp)2.Homogeneous Catalysis in Carbonylative Coupling Reactions 223 Buchwald et al. demonstrated palladium-catalyzed alkoxycarbonylation of aryl iodides with a thiourea-oxazoline type ligand under mild conditions (Scheme 31) [54]. Lei et al. 70 oC R COOEt N S N O R N A Scheme 31. demonstrated a mild. CO (1 atm) DMSO.2HBF4 as a catalyst for these conversions. followed by oxidative addition to Pd(0).1-benzoxazin-4-ones in good to excellent yields (Scheme 34) [56-57]. The protocol was applicable for variety of substrates providing good to excellent yield of desired heterocycles.224 Pawan J. Larock and coworkers described several annulation processes involving heteronucleophilic attack on the acylpalladium intermediate generated through intermolecular insertion of the internal . Patil and Bhalchandra M. 15 h O OH R Scheme 33. DMF R I + NHCOOEt R R + CO Pd (OAc)2. Tambade. The reaction is believed to proceed via in situ amide formation from o-iodoaniline and acid chloride. Pyridine n-Bu4NCl. Yogesh P. Cl R 2 equiv H2O 2 mol % Pd (OAc)2 4 mol % dcpp 2HBF4 1. R I NH2 + Cl O O R Pd(OAc)2 CO R N O R Scheme 34. Bhanage dcpp. and intramolecular cyclization. The system is applicable for the synthesis of variety of aryl and hetero aryl acid derivatives at low CO pressure.5 equiv K2CO3. CO insertion. Starting from o-iodophenols or N-substituted o-iodoanilines and internal alkynes. MISCELLANEOUS REACTIONS Alper et al. Hydroxycarbonylation of aryl chlorides. Pyridine n-Bu4NCl. R I R O O + R OH R + CO Pd (OAc)2. The reaction works well in the absence of phosphine containing ligands. 100-120 oC. DMF Hydrolysis N H R O Scheme 35. Synthesis of coumarins and 2-quinolones using carbonylation reaction. Palladium catalyzed carbonylation of acid chlorides with o-iodoanilines. reported carbonylation of acid chlorides with o-iodoanilines to producedsubstituted-4H-3. 3-dihydro-1. The reaction occurs at ambient pressure and temperature using Pd(PPh3)4 as a highly active and regioselective catalyst. Under optimized settings coumarins and 2-quinolones were obtained in moderate to good yields.Homogeneous Catalysis in Carbonylative Coupling Reactions 225 alkyne into s-aryl palladium complex followed by CO insertion for the synthesis of heterocyclic compounds. which proceeds with remarkable site selectivity to afford a variety of five. followed by oxidative addition. of pyridine and nBu4NCl. (Scheme 36) [61]. Synthesis of 3-Substituted-3. Orito et al. Pd (OAc)2 Cu (OAc)2 CO (1atm). demonstrates palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides to produce quinazolin-4(3H)-ones in single step (Scheme 38) [63].or six-membered benzolactams from secondary o-phenylalkylamines in a phosphine-free catalytic system using Pd(OAc)2 and Cu(OAc)2 in an atmosphere of CO gas containing air (Scheme 37) [62]. A wide variety of substituted quinazolin-4(3H)-ones were prepared in 63-91% yields by the palladium-catalyzed cyclocarbonylation of o-iodoanilines with imidoyl chlorides and carbon monoxide. reported Pd(II)-catalyzed direct aromatic carbonylation. The carbonylative insertion process occurs in good to excellent yields with total regioselectivity at the N-S bond of benzisothiazole precursor and the reaction tolerates a number of substituents.3-benzothiazin-2-ones via palladiumcatalyzed carbonylation of 2-substituted-2. reflux (CH2)n NR n = 1 or 2 (CH2)n NR O Scheme 37.2-benzisothiazoles was reported by Alper et al. The selected reaction conditions utilize Pd(OAc)2. Palladium catalyzed carbonylation of benzisothiazoles. These annulation processes represents the first examples of intermolecular insertion of an alkyne on a s-aryl palladium complex occurring in preference to CO insertion and allow the exclusive formation of coumarins and 2-quinolones (Scheme 35) [58-60]. under CO (1 atm) in DMF at 100–120 °C. toluene. including primary and secondary alkyl groups and benzylic and naphthylmethyl functionalities. 2 equiv. The protocol was used for synthesis of wide range of heterocycles by C-H activation of phenylalkylamines without use of any expensive aryl halides under phosphine free conditions. Alper et al. The reaction is believed to proceed via in situ formation of an amidine.4-dihydro-2H-1. Synthesis of benzolactams via palladium catalyzed carbonylation. 80 oC Pyridine S N O R Scheme 36. S N R Pd (PPh3)4 CO (300 psi). CO insertion and intramolecular cyclization to give the substituted . Bhanage quinazolin-4(3H)-ones. I OH Pd (OAc)2 / Xantphos + CO Et3N. NEt3 100 oC. Blaquiere et al.HCl NH2 OH Deferasirox Scheme 39. 20 h O R R' Scheme 40. or 80–94% per bond for the four bonds created. Beller et al.226 Pawan J. . this method compares favourably with direct C-H arylation technology. Synthesis of deferasirox via Pd catalyzed multicomponent carbonylation reaction. Tambade. ROTf + CO + R' [(Cinnamyl) PdCl2] dppp toluene. Palladium catalyzed carbonylative Heck coupling reactions. This method represents a “missing link” between the already established carbonylative Suzuki and Carbonylative Sonogashira reactions. Recently. reported Carbonylative Heck coupling reactions of aryl and alkenyl triflates with aromatic olefins (Scheme 40) [65]. Yogesh P. As such. Patil and Bhalchandra M. mild reaction temperatures and low carbon monoxide pressure. DMF 4 . This approach features a wide scope. Total yields range from 41% to 79%. R I + CO + NH2 Cl R1 O N R2 Pd(OAc)2 / PPh3 R N N R1 R2 Scheme 38.Hydrazino benzoic acid HOAc N HOOC OH N N HO + NH . The products obtained represent useful building blocks for the synthesis of numerous biologically active compounds. Cyclocarbonylation of o-iodoanilines with imidoyl chlorides. The developed protocol was applicable for the synthesis of wide range of substituted quinazolin-4(3H)-ones. The protocol was applicable for the synthesis of wide variety of heterocycles and also underscored for the synthesis of druglike and/or pharmaceutically relevant molecules from commercially available materials. reported a novel strategy for the palladium-catalyzed multicomponent synthesis of trisubstituted triazoles via carbonylation reactions (Scheme 39) [64]. Starting from easily available aryl and alkenyl triflates the corresponding unsaturated ketones are obtained good yields. Soc. J. N. [7] Roelen. 1520-1524. M. carbonylation reactions using such catalysts are indeed an area yet to discover. Plenum Press: New York. Rhodium catalysed hydroformylation. G. H. 45. [12] Labadie. A. Kluwer. [9] Olah.. G. [3] Skoda. The application and chemistry of catalysis by soluble transition metal complexes (II Eds). mbH Oberhausen. [6] Cornils. R. M. T.Homogeneous Catalysis in Carbonylative Coupling Reactions 227 CONCLUSION This review summarized the recent developments in the area of palladium-catalyzed carbonylative coupling reactions of aryl halides and related starting materials in homogeneous media. A catalystfree synthesis of asymmetric diaryl ketones from aryltins. [10] Silbestri.. U. Wiley. (1973). having a plethora of new synthetic catalytic methods for carbonylative coupling reactions. R... Chem. M. J. 6. direct synthesis of carbonyl compounds. Int. Tetrahedron. (1983). Thus. (2000). various catalytic carbonylation reactions have been developed over the past decades. 1097-1119. A. Chem. M. B. P. [11] Neumann. the development of asymmetric catalysts for carbonylation reactions needs to be explored. (1943). Since the original work of Heck and co-workers. J.. L. 1944.. U... J. 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Catálises e Cinética.Federação das Industrias do Estado do Paraná. Fourier Transformed Infra-red spectroscopy and electronic spectroscopy. Tel.: + 55 16 3351 8214.ufscar. Universidade Federal de São Carlos. Poehler ISBN: 978-1-61122-894-6 © 2011 Nova Science Publishers.3-xylylenediamine] are reported.R. The oxidation catalytic of methyl phenyl sulfide with the complexes in solution and heterogeneisated by means of supporting on alumina was studied. can be used as an intermediate in the fabrication of pharmaceuticals. characterization and catalytic study of Oxovanadium (IV) complexes and yours precursors Schiff bases [N. CHARACTERIZATION AND CATALYTIC STUD OF OXOVANADIUM (IV) COMPLEXES WITH TETRADENTATE SCHIFF BASES A. E. DQ. electronic spectroscopy and 1H and 13C Nuclear Magnetic Resonance spectra. Brazil. [N. the catalytic products were characterized by 1 H Nuclear Magnetic Resonance and Fourier Transformed Infra-red spectroscopy. Dockal2. * Corresponding author.3-phenylenediamine] and [N.N’-bis(salicylidene)-1. São Carlos. E-mail address: apamarques@liec. melting points. The Schiff base ligands were characterized by elemental analysis. The product of catalytic reaction. 3 SENAI .In: Homogeneous Catalysts Editor: Andrew C.P. Centro Cívico.br . Skrobot3 LIEC – CMDMC. Universidade Federal de São Carlos. Brasil 2 Laboratório de Sínteses Inorgânicas. Chapter 8 SYNTHESIS.3-xylylenediamine] presents the best catalytic activity in homogeneous system probably due to its flexibility that favors the access of the substrate to active center in the catalysis. Brazil. melting points. Fourier Transformed Infra-red spectroscopy. SP.A.N’-bis(salicylidene)-1. Ieda Lucia Viana Rosa1 and F. The catalytic reactions were accompanied by gas chromatography. The oxovanadium (IV) complexes were characterized by elemental analysis.C. 4]. Dockal. 8-10.P. N.3-phenylenediamine and [N.N’-bis(salicylidene)-1. Marques. 16]. 1. separation and recycling. Enzymes containing vanadium as an essential element were isolated in the 1980’s.234 A.2-phenylenediamine. 2. named (salophen).N’-bis(salicylidene)-1. . The development of new supported catalysts which combine the properties of homogeneous catalysts with the benefits of heterogeneisation is of prime interest to the chemical industry at present. Keywords: Oxovanadium (IV) complexes. Nowadays. and studies in clinical trials in human beings with organic transition metal complex are been developed [5]. Schiff base ligands.3-xylylenediamine]. E. are the subject of various studies in our laboratory [6. INTRODUCTION Vanadium has aroused the interest of researchers since the discovery that various marine species have this metal as an essential element [1]. 14] Heterogeneisation of homogeneous catalysis. 12]. coupled with the potential for automation which has become recognized by more and more rank-and-file industrial and academic synthetic chemistry [13. but also offer considerable economic benefits if recycling and re-use would be possible [15. 8]. Oxovanadium (IV) complexes containing tetradentate Schiff bases have been the subject of various studies [6-12].N’bis(salicylidene)-1.1 Materials All solvents and reagents were of commercial grade unless otherwise stated and were purchased from Merck and Aldrich. The use of chiral Oxovanadium (IV) complexes in the preparation of chyral sulfoxide for the medicine industry has been widely studied [7]. In this work. However. we describe the preparation and characterization of the Oxovanadium (IV) complex of the tetradentate Schiff bases: N. These enzymes are able to exercise the activities of nitrogenase and bromoperoxydase [1]. Synthesis. Ieda Lucia Viana Rosa et al. The catalytic activity of the [VO(salophen)] [VO(salmphen)] and [VO(salmxylen)] in the oxidation of the methyl phenyl sulfide in acetonitrile. Tetradentate Schiff base complexes of Oxovanadium (IV). EXPERIMENTAL 2. not only solve the basic problem of catalyst separation. Several vanadium compounds have recently been investigated in animal model systems as treatment for diabetes [3. the process of support of the complex can become the active center more impeded and damage the reaction. recovery. respectively.R. Methanol (MeOH). VO2+. a lot of papers deal with the vanadium biochemistry [2]. The advantages are arising from ease of handling. Catalytic Reaction. Ethanol (EtOH). (salmphen) and (salmxylen). in some catalytic reactions. using tert-Butyl-Hydroperoxide as oxygen donnor in a homogeneous system and supported on γ-alumina was studied. dimethylsulfoxide (DMSO) and chlorophormio (CHCl3) were used as received. One area of great interest also is the role of the vanadium species in the oxygen-atom or electron transfer reactions [2. the heterogeneisation of system can damage the reaction. acetonitrile (ACN). through the complex supported in alumina.A. After cooling slowly to room temperature. H) were performed in an EA-1108 CHNS-O Fisons apparatus. The complex was purified by Soxhlet extraction using ethanol. 1.Synthesis.0 mmol of the Schiff base ligand and sodium acetate trihydrate (8. 2. The 1H and 13C Nuclear Magnetic Resonance (NMR) spectra of the free ligand in DMSO were obtained using a Bruker ARX 400 MHz 9. [VO(salmphen)] and [VO(salmxylen)] were prepared and purified using an adaptation of the methods described previously [6-9]. After cooling slowly to room temperature.2-phenylenediamine. the salicylaldehyde (20 mmols) was added in this mixture after 30 min. 2. Electronic spectra were recorded in the 270-800 nm range in CHCl3 using a MultiSpec-1501 Shimadzu instrument.250 g of support γ-alumina in dichloromethano (25mL). the resulting precipitate was collected by filtration. The solid was filtered .→ [VIVO(Schiff base)] ↓ Scheme 1. N.1mmol) was added to a mixture of 0. Characterization and Catalytic Stud of Oxovanadium … 235 2.0mmol) in 20mL of distilled water was added to a hot ethanol solution.5 Preparation of the Catalysts [VO(L)]-Alumina [VO(L)] (0. Although a precipitate formed almost immediately.2 Synthesis of Schiff Base (L) The Schiff bases were prepared by condensing of the diamine (1. in alcoholic solution (ethanol) [6-9]. This mixture was stirred and heated for 3 h. 50mL.4T spectrometer. the mixture was refluxed with stirring for 3h. the resulting precipitate was collected by filtration.3-phenylenediamine and 1. Schiff base + 2 NaOAc → (Schiff base)2. 2. washed with 20mL of distilled water and 10mL of ethanol twice. A solution of Oxovanadium (IV) sulfate (4. The diamine (10 mmol) was added to a hot ethanol solution. The purified complex was dried in vacuum at room temperature.4 Characterization of Schiff Base (L) and [VIVO(Schiff Base)] ([VO(L)]) Elemental analyses (C.0 mmol). 50mL. washed with 20mL of distilled water and 10mL of methanol twice.3 Synthesis of [VIVO(Schiff Base)] The complex [VO(salophen)]. containing 4.3-xylylenediamine) with the salicylaldehyde in a 1:2 proportion. The ligands were dried in vacuum at room temperature. Fourier Transformed Infra-red (FTIR) spectra of the free ligand and the complex were recorded in the 250-4000 cm-1 range as pressed discs (1% by weight in CsI) with a Bomem Michelson 102 FTIR spectrophotometer.+ 2 HOAc + 2 Na+ VO2+ + (Schiff base)2. according to Scheme 1. The reactional system was stirred and warm at 60°C for 150min. 34mmol) were added in ACN (25mL).A. and washed thoroughly with distilled water till the washings were colorless. The yield of the purified complex and the ligand were listed in Table 1. Nitrogen was used as the carrier gas with a hydrogen flame ionization detector.236 A. 2. internal diameter. 0. E.3mmol) and 0. The oxidation products yields were calculated by the chromatograms area. a 15 °C min−1 heating rate was used.88 mL.3 mmol). The supported solid [VO(L)]-alumina obtained was dried at 100 °C overnight. both from TA Instruments. The Schiff bases salophen salmphen and salmxylen and yours respectively complexes were stable in air. This exchange procedure was repeated twice.R. 7mg and a platinum sample holder under a N2 flow of 90mL min−1.6. RESULTS AND DISCUSSION The synthesis and characterization of the Schiff bases salophen and salmphen and yours complexes were described previously elsewhere [10].25 μm Megabore® film. The melt points of the ligands Schiff base were minors that 100°C and of the complexes were higher 360°C and with short temperature variation. The elemental analyses indicate that the complex is monomeric specie formed by coordination of 1 mol of the metal ion and 1 mol of the Schiff base ligand. 5. 3. 2. solution.P.7. Catalysts Characterization Scanning electron microscopies (SEM) were recorded on Stereoscan 440.62mL. both in solution and in the crystalline state. Dockal. Gas chromatographic analyses were carried out on a Shimadzu chromatograph. 30 m. the small interval of temperature is one indicative that the compounds are pure (Table 1). Ieda Lucia Viana Rosa et al. Marques. 0. 5.25 mm) was packed with 0. The DB-1 capillary column (length. Oxidation of Methyl Phenyl Sulfide Methyl phenyl sulfide (0. The oxidation products were characterized by 1H RMN (CHCl3) and IR (1% by weight in CsI. In all experiments. cm-1).5 molar aq. . To this mixture was added the oxygen donor tert-Butyl-Hydroperoxide (t-BuOOH) (0. using sample mass of ca. 5.14g of the catalyst solids [VO(L)]alumina or the free complex [VO(L)] (0. the yield variation between ligand and your respectively complex is probably due to differences in the solubility of these compounds. The values obtained for elemental analysis were consistent with the calculated ones to the molecular weight corresponding (Table 1) and the graphic of the structures of the Oxovanadium (IV) complexes in Figure 1.169g. Thermogravimetric analysis (TGA) were carried out using the a TGA-951 thermogravimetric unit coupled to a TGA-2100 thermal analyzer. 3) 7.8(3.3) 74.28) C22H20N2O2(344.7) 6.4(4.7(64.) (%) C 63.7) 63.2(7.4) N 7.3(7. The FTIR spectra of the free ligands and the complexes show various . Structural representations of the complexes: [VO(salophen)] (a). Calc.28) [VO(salmxylen)] C22H18N2O3V(409.3) 8.6) H 3.7) 3. [VO(salmphen)] (b) and [VO(salmxylen)] (c).7(3.33) -1 237 Anal. Compound [VO(salophen)] salmxylen Formula(Mol.3) 62. Found (Anal. melting point and elemental analysis of Oxovanadium (IV) complexes and the salmxylen ligand.0(8.4(5.8) Yield (%) 99 84 98 86 M. P.8(63. Data of yield.1) 6.3(63. Weight) (g mol ) C20H14N2O3V(381. Characterization and Catalytic Stud of Oxovanadium … Table 1.8) 4.2(76.Synthesis.41) [VO(salmphen)] C20H14N2O3V(381.8(6. (°C) >360 >360 62 >360 HC O N O V O N CH (a) HC O N O V N CH O (b) H2C HC O N O V CH2 N CH O (c) Figure 1. Figure 2 presents the FTIR spectra in the 200-4000cm-1 range of (salmxylen) (A) and [VO(salmxylen)] (B). Dockal. 18. 1200 1280.A. The more important difference observed in the electronic spectra of the Oxovanadium (IV) complexes. 18. 19]. 1116 1312. 18. 9. trichloromethane (TCM) or dimethyl sulfoxide (DMSO). at 361nm is assigned to n→π* transition involving molecular orbital of the C=N chromophore and the benzene ring [8. 17] The complex C=N stretching frequency is expected to appear in lower frequencies when compared to the ligand.P. The π→π* transition of the C=C and C=N chromophores normally occur between 270 and 300nm [21].e.R. 8-10. The isolated benzene ring exhibits three characteristic absorptions around of 196-204. Table 2. 23]. In the complex it was observed . Relevant IR frequencies (cm-1) of the ligands and Oxovanadium (IV) complexes. 22. 210-244 and 255-278nm assigned to π→π* type transitions [21]. i. around of 420nm. 23]. The band in 611cm-1 is assigned to ν(V-N) and 450cm-1 is assigned to ν(V-O) as reported in references [6. 22. recorded in the 270-800nm region. 8-10. 1124 ----980 ----985 ----968 ----611 ----542 ----638 ----450 ----389 ----457 Table 3 lists the bands of the electronic spectra of the Schiff base ligands in solutions of acetonitrile (ACN). 20. Figure 2. 20. As it noticed in Figure 2.238 A. 1125 1366. The weak band. as a shoulder. indicating a decrease in the bond order due to the coordinate bond of the metal with the azomethine nitrogen lone pair [1. The C-O stretching frequencies were observed as strong bands at 1316 and 1116cm-1 for the ligand. 21]. compared to the free ligands. 12. the C=N stretching frequency is observed at 1617cm-1. 21]. Marques. 24-27]. Table 2 lists the most important and characteristic bands of the FTIR spectra of the samples. E. The C-N stretching frequency has been reported in the 13401020 cm-1 region [17. The band around of 315-343nm observed in the ligand is assigned to π→π* transition. For the complex they were noticed at 1312 and 1125cm-1. 1193 1380. 1197 1279. 17. Ieda Lucia Viana Rosa et al. In this case the band occurs near 1151cm-1 for the ligand and around 1154cm-1 for the respective complex. bands in the 200-4000cm-1 region. Compound salmxylen [VO(salmxylen)] salophen [VO(salophen)] salmphen [VO(salmphen)] ν(C=N) ν(C-N) ν(C-O) ν(V=O) ν(V-N) ν(V-O) 1634 1617 1616 1607 1622 1617 1151 1154 1315 1310 1215 1217 1316.The characteristic V=O stretching frequency in the Oxovanadium (IV) complexes appears as a medium-to-strong band at 980cm-1. theses spectra exhibit between four and two bands. In similar compounds the C-O bands occur at 1390-1330 and 12601000cm-1 [17. These bands were observed as new absorption peaks of the complex and are not present in the spectrum of the free ligand. The C=N stretching frequencies in the (salmxylen) occur at 1634cm-1 as reported for similar ligands [8-10. which involves molecular orbitals essentially localized on the C=N group and the benzene ring. 17. is the absence of the band assigned to pπ→d transition. within the 9501000cm-1 reported for similar Oxovanadium (IV) complexes [6. 25-27]. FTIR spectra (200-4000 cm-1) of [(salmxylen)] and [VO(salmxylen)]. salmphen and salmxylen in solutions. **band out of area permitted for the solvent. Table 3. Ligand Attributions ACN * 343 274 210 196 * 328 267 226 204 * 315 255 215 ** Absorption Data λ(nm) Solvent TCM * 331 261 244 ** 361 328 262 243 ** * 317 257 ** ** DMSO * 343 278 ** ** * 316 ** ** ** * 316 ** ** ** salmph n→π∗ (C=N) π→π∗ (C=N) π→π∗ (C=C) π→π∗ (C=C) π→π∗ (C=C) n→π∗ (C=N) π→π∗ (C=N) π→π∗ (C=C) π→π∗ (C=C) π→π∗ (C=C) n→π∗ (C=N) π→π∗ (C=N) π→π∗ (C=C) π→π∗ (C=C) π→π∗ (C=C) saloph salmxy *band absent or hidden.Synthesis. The strong absorption band around of 278-316nm observed only in the electronic spectra of the complex is assigned to π→π*of the benzene ring [8-10. [(sal)2(xilen)] C=N [VO(sal)2(xilen)] V=O C=N 4000 3000 2000 1000 Figure 2. 21. Characterization and Catalytic Stud of Oxovanadium … 239 the same band at the same wavelength. Absorption data (nm) of electronic spectra of the Schiff base salophen. . t.8 63. 4 5 3 2 1 7 OH N 8 10 11 12 9 10 11 HO N 8 2 1 7 3 4 5 6 6 Figure 3.240 A. These values are in agreement with other similar Schiff base ligands [8.9mc 7. 27].5 138. respectively.30-6. The free ligand showed broad peaks between 7. The sign of the carbon belonged to -CH2N group appears at 63. The 13C NMR spectrum of the tetradentate Schiff base in DMSO shows the peak concerned to CH=N at 165. The 1H NMR spectrum of the Schiff base in DMSO shows the peak characteristic of the OH as a singlet sign at 13. E. Ieda Lucia Viana Rosa et al. d.P.A. Numbering system of the carbon atoms for the RMN assignments.0 126.6 129.45 and 6.1 131.43ppm and 4.43s 4. mc.1 ppm.8ppm.33d 6. 21].45s --7.1 165. The 1H and 13C NMR data of the Schiff base obtained from its spectra are given in Table 4 and numbering system is presented in Figure 3.38s 1 salmxylen 13 C NMR (ppm) 118.87t 13.9mc 7.R. triplet. The singlets at 8.4 118. Atom C1 C2 C3H C4H C5H C6H C7H C8H C9H C10 C11H C12H δOH s H NMR (ppm) ----7.0 132. singlet.38ppm.30-6.30-6. multiplet complex .0 and 161.9mc 7. doublet of doublets.79s 7.87ppm due to hydrogen bonded phenolic protons [8. doublet.30-6.6 127. Table 4.0 ppm are assigned to the phenyl.79ppm correspond to the CH=N and -CH2N.0 --- . 1H and 13C NMR data of the salmxylen ligands (chemical shifts in ppm).9mc 8.0 117. Dockal. The peaks between 117. dd. Marques.8 161. Hom mogeneous. After 5 hou urs of reaction n only 6 mol% % of the sulfid de was oxidize ed to sulfoxid de when the [V VO(salmphen) )]-alumina cat talyst was use ed. re espectively. [VO(salmphen)]-alumina a and [VO(salmxylen)]-alu umina. and a 87 mol% % for [VO(salophen)]. Figure 5 pr resents the pr rogression of the t oxidation reactions of methyl m phenyl sulfide in alumina and th he presence of o free [VO(L L)]. Char racterization and a Catalytic Stud S of Oxova anadium … 241 (a) (b) Fi igure 4. s Table e 5 presents th he results of th he catalytic oxidation of m methyl phenyl sulfide for the studied syst tems. After one o day it was s observed an increase in th he product yield. probab bly due to the low co oncentration of o [VO(samxylen)] in this su upport. it can be noticed that th he alumina is thermal stabl le material. y which values were e 73. around of f ten times mo ore that the ho omogeneous sy ystem.10 0μm. . [VO(L)]pure γ-Alum mina.Sy ynthesis. Figure 5 and Table 5 shows that th he catalytic sy ystems consisting of [VO(s salophen)]-alu umina and γ-a alumina witho out the comple ex. the expected lo oss of mass s due to the organic li igand of the e catalysts [V VO(samxylen) )]-alumina was w practical lly impercep ptible. the heterogeneous syste ems present ac ctivity catalyti ic only at reac ctions times lo onger. [VO(salmp phen)] and [V VO(salmxylen n)]. while 69 mol% and 22 2 mol% of the e sulfoxide w produced for [VO(salm were mphen)] and [V VO(salophen)] ] homogeneou us catalysts. Howev ver. [V VO(salophen)] ]. Figure 4 presents SEM images of [V VO(salmxylen) )]–alumina (A A) and alumin na (B). did not pr resent any ac ctivity on the e catalytic ox xidation of methyl m phenyl sulfide. H However. showed be more adequa ate because af fter 24 and 48 8 hours of reac ction this syst tem produced 87 and 92 mo ol% of sulfoxi ide. and heter rogenized Oxovanadium (I IV) complexes. The SE EM image sh how the varia ation in the surface of the e alumina afte er the adsorpt tion of the [V VO(salmxylen n)] and the di istribution ho omogeneous of o the comple ex in the surf face of the al lumina. using t-B BuOOH as ox xygen donor and a ACN as solvent. 75. 29]. The [VO(salmx xylen)] homogeneous catal lysts not presented catalyti ic activity in 5 hours. SEM im mages of [VO(s salmxylen)]–alu umina (A) and alumina a (B) . How wever. co ompared with h [VO(salmxy ylen)] homoge eneous system m. present ted activity on n the catalytic c reaction. it sy ystem presente ed an less incr rease in the su ulfide oxidatio on after 24 hou urs of reaction n (8 mol%) an nd at 48 hou urs produced 15 mol% of sulfoxide. al thermal ana alysis has been used to cha aracterize the complex hey yerogenized Differentia [2 28. the het terogenized sy ystem showed considerable conversion on nly after 24 hours h of react tion to [VO(s salmphen)]-alu umina and [V VO(salmxylen) )]-alumina. m more longer tha at the homoge eneous systems. Th he [VO(salmx xylen)]-alumin na system. Throu ugh this analy ysis. [VO(salmphen)]-alumina (-). the oxidation of this occurs more easily.3 of [VO(salmphen)] becomes the active center more unimpeded than the bridge in position 1.Accompaniment of the oxidation reactions of methyl phenyl sulfide in the presence of [VO(salmphen)] (--). respectively. Marques. whereas the catalytic [VO(salmphen)] system produced 42% of sulfoxide. Ieda Lucia Viana Rosa et al. It was observed in [VO(salophen)] and [VO(salmphen)] systems the formation of two products for the sulfide oxidation. consequently. what it facilitates the approach of the substrate to active center. [VO(salmphen)] and [VO(salmxylen)]-alumina. This characteristic suggests that the bridge in position 1. [VO(salmxylen)]-alumina (--).A. The occurrence of the formation of sulfoxide and sulfone in the systems [VO(salophen)] and [VO(salmphen)] in solution it suggests that the active center possess high degree of desprotection what it facilitates the approach of the substrate. corresponding to 75 mol % of sulfoxide and 20 mol % of sulfone to [VO(salophen)] system and 83 mol % of sulfoxide and 17 mol % of sulfone to [VO(salmphen)] system. The results for [VO(salmxylen)]-alumina system show a differentiate increase after this time (92 mol%). compared to the 5 hours reaction (0 mol%). 100 80 Conversion (%) 60 [VO(salophen)]-alum and γ−alum [VO(salmphen)]-alum [VO(salmxylen)]-alum [VO(salophen)] [VO(salmphen)] [VO(salmxylen)] 40 20 0 0 50 100 150 200 250 300 1000 1500 2000 2500 3000 Time (min) Figure 5. diminishing the formation of product. 100% for [VO(salmphen)] and 92 mol% for [VO(salmxylen)]-alumina. [VO(salophen)] (--).P. These oxidation reactions were monitored for one day when the conversion was stabilized at 95 mol% for [VO(salophen)]. Dockal. It was observed that in the homogeneous catalytic system with intermediate structural flexibility and in the heterogeneous systems that possess complexes with additional flexible structures present better catalytic activity. In first the 240 minutes (four hours) the [VO(salophen)] does not promote the oxidation of the sulfide. These observations suggest that the alumina .2 of [VO(salophen)].242 A. however at long time of reaction both had converted sulfide to sulfoxide and sulfone. in the system [VO(salmxylen)] in solution the structure possess a distortion able to hinder the approach it substrate to the active center.R. [VO(salophen)]-alumina and γ-alumina pure (--). and. E. [VO(salmxylen)] (--). Methyl phenyl sulfide conversion (mol%) in the [VO(L)]. forming sulfone with sub-product. Long reaction time favors the re-oxidation of substrate. . consequently.48. Time (min) [VO(salmxylen)] Methyl phenyl sulfide conversion (mol%) [VO(salmphen)] [VO(salophen)] Pure γalumina homog. The S=O (νS=O) and SO2 (νSO2) stretchings are characterized by the bands at 1089 and 1161cm-1.Synthesis. Table 5. it is suggested that long time of reaction is not recommended to the oxidation of sulfide to sulfoxide. In the homogeneous system the complex is free and its distortions can turn the active center impeded.06ppm assigned to sulfide. The 1H NMR showed peaks near 2. in this case [VO(salmxylen)].81 and 3. 0 0 0 0 0 87 92 3 18 21 42 69 75 100 homog. The sulfide is characterized by S-C stretching (νS-C) around 740cm-1. Because of this fact. These data are in agreement with chromatographic data. where L: salmxylen. where the homogeneous systems present sulfoxide and sulfone as catalytic products only at long times of reactions (more than 24 hours). 0 0 0 0 0 0 0 0 0 0 0 0 0 0 The products of oxidation of methyl phenyl sulfide were characterized by FTIR and 1H NMR data. being thus. the homogeneous catalysis is more efficient that the heterogeneous catalysis because promotes the oxidation in less time reaction. Characterization and Catalytic Stud of Oxovanadium … 243 support becomes the molecule most rigid and with the more impeded active center. respectively. heterog. sulfoxide and sulfone. salmphen or salophen. 60 120 180 240 300 1440 7200 0 0 0 0 0 8 34 heterog. 2. thus intervening with the catalytic reaction. respectively. the capable complex of bigger distortion are what it possess betters conversions. 0 0 0 0 6 12 43 0 0 0 0 22 73 88 homog. heterog. [VO(L)]-alumina and pure γ-alumina. P. R. H. R. A. E. C.). American Chemical Society Symposium Series 1998. D. The catalysis results indicate a good activity of the catalysts [VO(L)] and [VO(L)]-alumina for the oxidization of methyl phenyl sulfide to sulfoxide. L. Sherrington.244 A. REFERENCES [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] D. Dockal. Benedettí. Carrano. Souza. Aranha. however. 99. R. Ieda Lucia Viana Rosa et al. Coordination Chemistry Reviews 1999. 10. Dockal. 201. Viana Rosa. A. M. G. Ramos. R. 61. Castellano. 45. Transition Metal Chemistry 1996. 43. Birmingham. A.R. Tracey. J. 370. CONCLUSION The results showed indicate that the synthesis of ligand and complex were efficient. Zamian. A. C. Hodge. 182. Inorganic Chemistry Communications 2007. I. Inorganic Chemistry 1986. Marques. in Solid Phase Synthesis (Ed. The catalytic study demonstrated that pure alumina and [VO(salophen)]-alumina were not good catalysts in the oxidation of methyl phenyl sulfide. 25. with good rate conversion. P. M. The [VO(salmphen)] system. S. 237. 1990. 353. Lonashiro. E. 14. Coordination Chemistry Reviews 1991. Journal of Molecular Catalysis A: Chemical 2003. 2561. Romera. The homogeneous system was the best system to oxidation reaction of sulfide to sulfoxide. E. Zamian. Butler.H. C. Thermochimica Acta 2007. Orvig. Epton). ACKNOWLEDGMENTS Financial support from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). . Polyhedron 1995. R. Dockal. J. 9. Salavati-Niasari. Herron. L. SPCC (UK) Ltd. Dockal.. Cavalheiro. C. F. Marques.: R. T. 202. E. showed an increase in the substrate oxidation compared to the other ones in minors time of reaction. E. Clark (Ed. C. Oliva. C. Crans. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Petrobras to cede the zeolite. A. 255. 123. S. J. 2411. H. M. the superior time of reaction favors the re-oxidation of substrate. probable because in [VO(salmphen)] system the catalytic active center is less impeded. C. Willksy. 1995. R. B. Kahn. Banitaba. 4714. J. G. R. M. dos Santos. G. A. L. Bolm. Zamian. Goldfine. 21. forming sulfone with sub-product. E. Thompson.P. A. Dockal. Chemistry of Waste Minimisation. McNeill. E. 711. Chemical Reviews 1999. 453. Dockal. R. P. Journal Inorganic Biochemistry 2000. David. 80. N.A. D. facilitating the oxidation of the methyl phenyl sulfide. Skrobot. 109. in: J. C. J. S. G. 242. D. Polymer-supported synthesis. P. H. K. Rehder. Coordination Chemistry Reviews 2003. Thermochimica Acta 1992. J. R. E. V. H. Crans. C. 1984. 235. 135. Academic Press. Introdution to Molecular Spectroscopy: theory and Experiment. Polyhedron 2001. [25] E. Ratnasamy. A. 7. 1247. in Vhairal Reactions in Heterogenous Catalysts. R. T. Wiley. Introduction to Infrared and Raman Spectroscopy. K. G. I. Pessoa. 115. Polyhedron 1997. R. B. 14. C. [26] B. A. Silverstein. Characterization and Catalytic Stud of Oxovanadium … 245 [16] D. Cavalheiro. J. D. Pini. Inc. Dockal. S. Spectrometric Identification of Organic Compounds. Ratnasamy. Patel. Tomaz. 90 627. 19. R. [22] J. C. 20. H. H. K. (Eds. Kolawole.: G. R. Journal American Chemistry Society 1968. D. P. Diegruber. Costa. P. Inorganic Chimica Acta 2003. Zamian. 261. P. I. T. T. G. Inorganic Chemistry 1980. [28] H. G. R. Shehata. [21] R. Pessoa. 356. Plath. P. 3211. Journal Molecular Catalysis A: Chemstry 1998. T. Bassler. . Petri. 1995.Synthesis. Inorganic Chimica Acta 2000. G. G. 121. Journal Coordenation Chemistry 1986. Henriques. C. Duran. Varkey. Morril. San Diego. [27] R. Correia. Schultz-Ekloff. S. R. F. [20] N. [19] K. C. Callahan. Daly. Brittain. 16. 2411. London. Dubois). Mastantuono. New York.. 1990. 14. M. C. 1970. [17] J. [23] A. I. A. Oliva. [18] G. 24. Academic Press. 1991. G. [24] J. Gillard. E. Castellano. Cavaco. El-Mahdey. 295. P. Felício.. Colthup. Salvadori. E. El-Dissouky. Henriques. 305. E. A. Dockal. P. Jannes. [29] S. Bosnich. J. V.. E. L. Wiberley. Polyhedron 1995. New York. Plenum Press. . Poehler ISBN: 978-1-61122-894-6 ©2011 Nova Science Publishers.In: Homogeneous Catalysts Editors: Andrew C. Republic of Korea (Tel. Inc. dendrimers have recently attracted a lot of attention.: +82 62 715 3463 & Fax: +82 62 9702304. Egypt (Tel. as biomolecules. but the present chapter is specifically focus on summarizing the major concepts for their properties as well as the most pronounced advances for their applications as supports for recoverable catalysts and reagents in asymmetric synthesis. ultrafiltration or ultracentrifugation. and as such they are. dendritic catalysts are nanosized. and Research Institute for Solar & Sustainable Energies (RISE). Buk-gu. 1 Oryong-dong. in other words. Kafr El-Sheikh University.and heterogeneous catalysis. Dendrimers have a number of potential applications. In particular. Republic of Korea Kafr El-Sheikh University. easily isolable from homogeneous reaction media by precipitation. School of Materials Science and Engineering. Kafr El-Sheikh 33516. Catalysis seems to be a research area in which promising applications for dendrimers may be developed. dendrimers will combine the advantages of homo. Faculty of Science.com) Department of Chemistry. and therefore they should lead to systems with activities similar to their monomeric analogues. Egypt ABSTRACT The use of soluble supports leads to recyclable catalyst systems that do not suffer from mass transfer limitations.and heterogeneous catalysis. Gwangju Institute of Science and Technology (GIST). Chapter 9 UNIQUE DESIGN TOOLS FOR THE SYNTHESIS AND DESIGN OF DENDRIMERS AS SUPPORTS FOR RECOVERABLE CATALYSTS AND REAGENTS AND THEIR APPLICATIONS IN ASYMMETRIC SYNTHESIS Ashraf A. Kafr El-Sheikh. or. filtration. This combination of features makes dendrimers suited to close the gap between homo. Gwangju 500-712.: +20 47 3215173 & Fax: +20 47 3215175) . El-Shehawy* Gwangju Institute of Science and Technology (GIST). * Department of Nanobio Materials and Electronics. Gwangju. Indeed. E-mail: elshehawy2@yahoo. since these well-defined macromolecular structures enable the construction of precisely controlled catalyst structures. Keywords: Dendrimers.e. monodisperse macromolecules. While several methods are being applied commercially.k.[1h. 5c.[1a. Heck and other Pd-catalyzed C-C bond formation. INTRODUCTION The development of well-defined catalysts that enable rapid and selective chemical transformations and can be separated completely from the products is still a paramount challenge.[1a. dialkylzinc addition to aldehydes and imines.3] The use of soluble supports leads to recyclable catalyst systems that do not suffer from mass transfer limitations.b.[1] The recent success of homogeneous catalysis is reflected in the number of applications that is known today both in the laboratory and in the industrial practice. In fact.6] Indeed. They are highly branched. Further key issues in this chapter relate to the deviating properties of dendrimers as compared to their linear macromolecular counterparts is considered.[1b. asymmetric catalysis. asymmetric synthesis.2] Catalysts supported on highly cross-linked polymer beads generally suffer from diminished activity compared to the homogeneous analogues.c] To give an answer to the question “what can dendrimers add to the field of catalysis?” we have to take a closer look at the ideal catalyst.f.c.k. and solubility of dendrimers.2.4] Dendrimers are a new class of polymeric materials. Many of the intriguing properties of dendrimers as well as their syntheses and possible applications are discussed in excellent books and reviews that have been published by various experts in the field. selectivity. the regular monodisperse . The structure of these materials has a great impact on their physical and chemical properties.j. hyperbranched polymers. El-Shehawy This chapter highlights some of the notable examples of the catalytic reactions using supported dendritic catalytic systems in such reactions as hydrogenation. chiral polymers. dendrimers offer a unique opportunity to combine the advantages of homogeneous and heterogeneous catalysis yet keep the well-defined molecular features required for a fully detailed analysis of the catalytic events. and therefore they should lead to systems with activities similar to their monomeric analogues.f-h. which results in low melt and solution viscosity. stripping.m. inorganic.5] As a result of their unique behavior. all “unit operations” for separation. alkyation. size. From a catalytic point of view the ideal catalyst is highly active and selective under mild conditions. the search for new approaches continues. It is possible to tune the structure. Furthermore. and crystallization. recoverable catalysts and reagents 1. and recyclability will be addressed.f-i.4a. l-n. or hybrid supports. the high degree of branching renders entanglement of the polymers impossible. A widely studied approach to facilitate catalyst product separation is the attachment of homogeneous catalysts to insoluble organic. 4a.[1a-d.k-n. hydroformylation. which is because of a reduced accessibility. Right from the start.i. dendrimers are suitable for a wide range of biomedical and industrial applications. chiral dendrimers.248 Ashraf A.d. catalyst destruction.h. dendritic catalysis.g. but so far there is not a single solution to the catalyst-product separation problem. stability. liquid-liquid separation or extraction. are being applied in industry. including distillation. shape. epoxidation.k.[1a-c. d.l. very stable and can be separated from the product using a relatively simple process. The intriguing properties of dendrimers in catalysis including activity.6a. This accessibility allows reaction rates that are comparable with homogeneous systems.Unique Design Tools for the Synthesis and Design of Dendrimers … 249 structure and multiarm topology of dendrimers inspired chemists to propose dendrimers with peripheral catalytic sites as soluble supported catalysts. A combination of these conceptual approaches might lead to systems with different catalytic centers. and thus the metal complexes. at the surface of the dendrimer. we do not want to present a comprehensive or complete overview on the reported dendrimers. instead. We hope to show that dendrimers are a unique class of macromolecules with a bright future ahead. Tomalia and Dvornic discussed the promising outlook of surface functionalized dendrimer catalysts. 6b. in which the substrate has to penetrate the dendrimer prior to reaction. Their globular shape makes these systems more suitable for recycling than soluble polymersupported catalysts. for example. These novel properties induced by the dendritic framework depend on the location of the functional group within the structure. in contrast to core-functionalized systems. However. keeping in mind that heterogeneous systems generally contain at least 1012 active sites per conglomerated particle. is closer to the monomeric homogeneous systems. A better formulation is that functionalized dendrimers potentially can combine the advantages of both homogeneous and heterogeneous catalytic systems. On the other hand. dendritic catalysts were proposed to be easily recyclable homogeneous catalysts. Further key issues in this chapter relate to the deviating properties of dendrimers as compared to their linear macromolecular counterparts. and focal-point functionalized (dendritic wedge) systems (see Figure 1). 4a. containing at most 1000 active sites. which are ideally suited for cascade reactions. Periphery-functionalized dendrimers have their ligand systems. One should distinguish periphery-functionalized (dendrimer or a dendritic wedge). if they also can provide systems that are either more active or selective or more stable than their homogeneous monomeric analogues? This would yield systems with interesting novel catalytic properties providing an intrinsic solution for the homogenous catalyst separation problem. the dendritic catalysts might show better performance than the monomeric species. 2. the periphery-functionalized systems contain multiple reaction sites and ligands. The most important one is the possibility to encapsulate guest molecules in the macromolecule interior.c. it is fair to state that the class of dendritic catalysts. The question is. several deactivation mechanisms operate by a bimetallic . but. The transition metals will be directly available for the substrate. however. and recyclability will be addressed. In 1994. we highlighted the most interesting studies that contribute to a better understanding the properties of dendrimers.m. which results in extremely high local catalyst and ligand concentrations.[7] Dendritic catalysts are often proposed to fill the gap between homogeneous and heterogeneous catalysts. Dendrimers have some unique properties because of their globular shape and the presence of internal cavities. The intriguing properties of dendrimers in catalysis including activity. stability. corefunctionalized. selectivity. Some of the notable examples on their uses as supports for recoverable catalysts and reagents in asymmetric synthesis will be discussed.[1c. DENDRITIC STRUCTURES In the first instance.8] In this chapter. Furthermore.[9] On the other hand. if a reaction proceeds by a bimetallic mechanism. whereas periphery-functionalized systems might suffer from relative low activity. Site-isolation effects in dendrimers can be beneficial for other functionalities. enzymes make use of these effects when substrates enter the active site of such systems. for example. apart from through polymerization reactions. which lead to products with a broad distribution of molecular masses (polydisperse).[12] Figure 1. ruthenium-catalyzed metathesis. corefunctionalized systems can specifically prevent such deactivation pathway.and periphery-functionalized dendrimers is the molecular weight per catalytic site. PURITY OF DENDRIMERS Higher generation dendrimers reach molecular masses that in earlier days had not been accessible through directed organic reactions. Catalytically active transistion metal complexes can be attached to the periphery (a). the three-dimensional structure of high-molecular compounds.[13] For reactions that are deactivated by excess ligand or in cases in which a bimetallic deactivation mechanism is operative. but very little is known about these effects. is of great interest. at the core (b). On the other hand. Hence.[10] palladium-catalyzed reductive coupling of benzene and chlorobenzene. since the dendrimers differ from biological macromolecules. . Effects of desolvation of the substrate during the penetration of the dendrimer might be of importance. In core. Core-functionalized dendrimers may benefit from the local catalyst environment created by the dendrimer. at the focal point of a wedge (c). such as dendrimers.[14] They are modelled on natural globular biomacromolecules that are able to perform certain functions as a consequence of their defined three-dimensional formation through hydrogen bonds. 3. the catalyst could benefit especially from the site isolation created by the dendritic environment.(and focal-point-) functionalized dendrimers. 1 active site) compared to 1 gL-1 (MW 20 000 Da. El-Shehawy mechanism. Much higher costs will be involved in the application of core-functionalized systems and application can also be limited by the solubility of the system (to dissolve 1 mmol of catalyst 20 gL-1 is required (MW 20 000 Da. In nature. Another significant difference between core.250 Ashraf A. for corefunctionalized systems the solubility of the dendritic catalyst can be tuned by changing the end groups. 20 active sites).[11] and reactions that involve radicals. and at the periphery of a wedgel. Unique Design Tools for the Synthesis and Design of Dendrimers … 251 such as proteins. implying that numerous reactions have to be performed on a single molecule. see Scheme 1). Experimental results. Thus. confirm this assumption. is reached and prevents any further reaction. the macromolecules transform into a more spherical shape from a certain generation upwards (depending on the core molecule. the divergent synthesis can be seen as the macromolecular approach toward dendrimers: the purity of the dendrimers is governed by statistics. every reaction has to be very selective to ensure the integrity of the final product.[19] so the knowledge gathered in this field should be considered when the perfection of dendritic structures is discussed. for example. dendrimer chemistry has become a part of supramolecular chemistry. the perfection of the final dendritic product is related to this synthetic approach. The reality of statistical defect structures is also recognized in the iterative synthesis of polypeptides or polynucleotides on a solid support (the Merrifield synthesis).18] Since every new generation of divergently produced dendrimer can hardly be purified. the inclusion of guest molecules and the viscosity. Path C illustrates “missed Michael additions (either by an incomplete . Simple calculations have shown that the area of an end group on this ellipse becomes continually smaller with an increasing number of generations until a critical branched state. According to an early theoretical work on idealized structures. Both approaches consist of a repetition of reaction steps. Generally. ellipsoidal shape. The synthesis of poly(propyleneimine)dendrimers (reaction A and B) and alternative unwanted reaction paths C and D. Scheme 1. the presence of a small number of statistical defects cannot be avoided. the dendrimer is grown in a stepwise manner from a central core. an average selectivity of 99. only result in 0. Consequently.5% per reaction will. two conceptually different synthetic approaches for the construction of high generation dendrimers exist: the divergent approach and the convergent approach. the so-called “Starburst dense packing”. each repetition accounting for the creation of an additional generation. in the case of the synthesis of the fifth generation poly(propylene imine) dendrimer (64 amine end groups. Assuming that in divergently synthesized dendrimers each branch is directed radially towards the outside and that the end groups lie on the surface of an ellipsoid. and therefore. branching multiplicity.[16] Hence. Bearing this in mind. the molecules are meant to be spherical constructions with a dense exterior and a loose interior with channels and cavities. in their three-dimensional covalently linked skeleton.[17. For example.995248 = 29% of defect-free dendrimer. and the length of the branch segment).[15] it was postulated that dendrimers of lower generations take a rather flat. 248 reactions. The two methodologies have their own characteristics. In the divergent synthesis. Thus. every MS spectrum has been simulated. and dielectric spectroscopy in the characterization of dendritic macromolecules. In the convergent approach. circular dichroism. only a small number of side products can be formed in each reaction.[17b] In the approach followed.[22] With the ESI-MS spectra of all five generation poly(propylene imine) dendrimers in hand. and chromatography techniques (HPLC. but these techniques cannot reveal small amounts of impurities in. X-ray diffraction. The characterization of dendrimers is rather complex due to the size and symmetry in these macromolecules. electrochemistry. the shape. SAXS. electrophoresis. DSC. which can be seen as dendrimers prepared in an “organic chemistry approach”. and to the polymer world because of their repetitive structure made of monomers. The simulation indicates a polydispersity (Mw/Mn) of 1. SEC) are widely used. SEC. the other pathway accounts for intramolecular amine formations (cyclizations). the difficulty of many reactions that have to be performed on one molecule has been overcome by starting the synthesis of these dendrimers from the periphery and ending it at the core.[21] Both of these dendrimer types are made via a divergent synthesis and are very suitable for electrospray ionization due to their polar and basic nature. Caminade and Majoral et als have been surveyed the main analytical techniques used for the characterization of the chemical composition. elemental analyses. a constant and low number of reaction sites are warranted in every reaction step throughout the synthesis. 15N. and the homogeneity of dendrimers. One pathway accounts for incomplete cyanoethylations and retro-Michael reactions.[18] This review included the use of NMR.20] and poly amido amine (PAMAM) dendrimers. El-Shehawy cynaoethylation or by a retro-Michael reaction). Thus. Laser Light Scattering. 23% for the fifth generation poly(propylene imine) dendrimer. and therefore. fluorescence. SANS. thus they benefit from analytical techniques from both worlds.[18. can be defect-free. All generations of poly(propylene imine) dendrimers with either amine or nitrile end groups have been analyzed with ESI-MS to quantitatively determine the importance of various side reactions. the morphology. 13C. intrinsic viscosity. EPR. IR. microscopy. ESI-MS has been used to identify the imperfections in both poly(propylene imine)[17b. all possible side reactions have been grouped in two different pathways that describe the formation of defect structures on going from one amine generation to the next (see Scheme 1). In this fashion. every new generation can be purified (although the purification of higher generation materials becomes increasingly troublesome).20] A progress in ESI (electrospray ionization) and MALDI (matrix-assisted laser desorption ionization) mass spectrometry allows for an in-depth analysis of dendrimers. convergently produced dendrimers.002 and a dendritic purity of ca. UV–Visible. As a consequence. Various NMR techniques (1H. especially. 31P).252 Ashraf A. Raman. 4. the significance of both pathways has been calculated using an iterative computing process. STRUCTURAL ANALYSIS OF DENDRIMERS Dendrimers pertain both to the molecular chemistry world for their step by step controlled syntheses. mass spectrometry. higher generation dendrimers. Paths C and D describe sefect reactions on going from one amine generation to the next. it seems more appropriate to discuss the . Since the perfect structure is the dominant species in the final product. a dendritic purity of at most 8%. The organic nature of the convergent approach results in defect-free dendrimers due to the limited number of reactions performed on the same molecule on going from one generation to the next.[25] MALDI-MS.. The small differences in structural features of the divergently produced structures on one hand and the convergently synthesized structures on the other are not expressed in differences in overall properties of these two classes of dendrimers (for example.[21a] Interpretation of the published data reveals.[16] and ESI-MS[26] are of lower generations.e. almost no impurities have been found. MALDI-MS studies on other divergently produced higher generation dendrimers (i. it is possible to purify intermediate generations. Metallodendrimers that have been studied with L-SIMS. Newkome-type dendrimers[23] and carbosilanes[24]) have also shown the presence of small numbers of imperfect structures.[28.[29] For a dendrimer with a mass of 39 969 D.Unique Design Tools for the Synthesis and Design of Dendrimers … 253 mixture in terms of dendritic purity than in terms of polydispersity (the dendritic purity is defined as the percentage of dendritic material that is defect-free). a polydispersity of 1. The exponential growth in the number of reactions to be performed on higher generations makes it virtually impossible to produce perfect dendrimers of generations beyond five or six. The defects are the result of the many reactions that have to be performed on the same molecular fragment.[27] Dendrimers synthesized via the convergent approach can be produced nearly pure. Reinhoudt et al. 5. these materials hardly contain defect structures. regardless the way in which they have been prepared. Additionally. have synthesized a third generation Pd(II) dendrimer with no observable defects in the mass spectrum. DENDRIMERS VERSUS LINEAR MACROMOLECULES Dendrimers are monodisperse macromolecules. all investigated dendrimers show a maximum in the intrinsic viscosity as a function of their molecular weight). almost no possibilities exist for the purification of intermediate generations. The polymeric nature of the divergent approach results in an accumulating number of statistical defect structures for every next generation. Virtually no perfect structures will be present in even higher generation materials. however. Therefore. can indeed be considered as the synthetic macromolecules with the most defined or most perfect primary structure known today. The classical polymerization process which results in linear polymers is usually random in nature and . Furthermore. ESI-MS studies on PAMAM dendrimers indicate defect structures arising from retroMichael additions and intramolecular lactam formations. as confirmed by MS data.0007 has been reported. dendrimers.[28] Moore’s phenylacetylene dendrimers have also been investigated with MALDI mass spectrometry. MALDI mass spectra of Fréchet-type dendrimers display very limited amounts of impurities.29] The detailed mass studies that have been devoted to the characterization of dendrimers indicate the most important difference between both synthetic methodologies at hand. and consequently. even though these materials have been produced in a divergent approach.[30] ESI-MS data on carboxylate-terminated phenylacetylene dendrimers subscribe the high degree of purity that can be attained for these dendrimers.[21] For a fourth generation PAMAM dendrimer (48 end groups). unlike linear polymers. dendrimers show some significantly improved physical and chemical properties when compared to traditional linear polymers. Differences in solubility and reactivity have also been found between poly(propylene imine) dendrimers with nitrile end groups and poly(acrylonitrile).[31] and PAMAM dendrimers. Similar results have been obtained by Fréchet et al.[36] In another study by the same authors. and this effect is explained by the declining influence of the end groups and the role of the entanglement molecular weight. El-Shehawy produces molecules of different sizes. the observed differences in solubility and reactivity have been attributed to the globular architecture of the dendrimers and the accessibility of the end groups of the dendrimer.[38] Although m-phenylenes would have been more appropriate linear analogues.[33. have studied several physical properties of polyether and polyester dendrimers. This typical growth pattern of dendritic molecules determines their solution properties and makes these properties deviate from those of linear molecules. The absence of entanglements in the higher generation materials is subscribed in a study on the melt viscosities of polyether dendrimers.254 Ashraf A. For linear polymers in general. who have compared dendritic polyesters with their linear counterparts. especially at higher molecular weights. When dendrimers in solution are considered.[31. as opposed to linear macromolecules. whereas their linear analogues are crystalline and only soluble in very polar solvents such as dimethylformamide and concentrated sulfuric acid.3. Due to this limited solubility. . the occupied volume of a single molecule increases cubically with generation. Fréchet et al.[39] In contrast to the linear polyesters. the intrinsic viscosity of dendrimers is not increasing with molecular mass but reaches a maximum at a certain dendrimer generation (for polyaryl ether. have compared the solubilities of 1. Because of their molecular architecture.[32] these maxima have been reported). causes the deviation in physical behavior of dendrimers from those of linear macromolecules. a leveling off of the Tg increase has been known for a long time. from a more extended arrangement for lower generation dendrimers to a compact and approximate globular shape for higher generation dendrimers. the dendrimers are soluble in a vast range of organic solvents. In contrast to linear polymers (that obey the Mark-Houwink-Sakurada equation). dendrimers are not significantly entangled. the growth pattern of dendrimers determines their physical characteristics. it appears that the melt viscosity is a physical parameter that is very dependent on the type of end group in the dendrimer. the study shows that the dendrimers have an enhanced solubility.34] Also in the solid state.[35] The increase in glass transition temperature (Tg) of the dendrimers levels off at higher molecular weights. whereas size and molecular mass of dendrimers can be specifically controlled during synthesis. The nitrile dendrimers are soluble in various organic solvents.[37] Miller et al. In general. Dendrimers have more end groups at higher masses. while dendritic polynitriles are easily hydrogenated. The intrinsic viscosity is a physical parameter for which such a deviation has been measured. The authors also note a marked difference in reactivity: the debenzylation of the polyesters via catalytic hydrogenation on Pd/C is only possible for the dendritic structures. the catalytic hydrogenation of poly(acrylonitrile) is not possible. whereas its mass increases exponentially. but. a phenomenon that is also observed for the linear analogues. it is believed that a gradual transition in overall shape.40] For all these cases.5-phenylene-based dendrimers with those of oligo-p-phenylenes.[3a] poly(propylene imine). Brunner designed dendritic catalysts containing dendritic phosphines which he called “dendrizyme” because of their hoped for similarities with enzymes. . This spatial arrangement had a crucial role since.Unique Design Tools for the Synthesis and Design of Dendrimers … 255 The uniqueness of dendritic architectures has been shown in an elegant study by Hawker et al. and equally important. The Hawker investigation solidly confirms that the physical behavior of dendrimers is different from that of linear polymers. Application of the rhodium complex (Rh:substrate ratio 1:50) to the hydrogenation of acetamidocinnamic a cid after 20 h at 20 bar H2 pressure led the desired product with a small enantioselectivity (enantiomeric ratio of 51:49). whereas the linear analogue is highly crystalline and poorly soluble in THF. The fourth generation polyaryl ether dendrimer and its linear isomer.1. in which polyether dendrimers are compared with their linear isomers (Figure 2).[41] Especially the fifth and sixth generation dendrimers display differing features when compared to their structural isomers. acetone.[44] A very interesting feature of this early study. and chloroform. The hydrodynamic volume of the fifth generation polyether dendrimer is approximately 30% smaller than that of its linear analogue. it shows that dendrimers need to have a certain size to display significantly different physical behavior. These reports belong to the pioneering works in catalysis using metallodendrimers that appeared in 1994. Asymmetric Transfer Hydrogenation to Olefins The first attempts to carry out asymmetric catalysis using chiral metallodendrimers were reported by Brunner’s group. the fifth generation dendrimer is completely amorphous (a Tg of 42 °C is recorded) and is soluble in a variety of organic solvents.1.[43] The ligand was coordinated to RhI in situ by reaction with [Rh(η4-COD)Cl]2.1. on the other hand. however. reported on a complex synthesized from a diphosphine core and dendritic branches containing menthyl groups (Figure 3).[42] Brunner et al. APPLICATION OF DENDRIMERS 6. 6. The difference is ascribed to a more compact backfolded globular structure of the dendrimer. hydrogenation with a dendritic diphosphine having dendritic wedges in 2. In addition. is that the rate of hydrogenation was higher in the presence of the dendritic diphosphine ligand having the dendritic wedge located at the meta position of the arene rings than with the nondendritic dppe. Asymmetric Transfer Hydrogenation 6.5-position exhibited a 300-fold rate decrease while the enantioselectivities remained very weak. Figure 2. 256 Ashraf A. Figure 4. Kakkar’s organophosphie dendrimers with phosphorous atoms at the focal points (up to P46 on the figure). El-Shehawy Figure 3. Brunner’s dendrizyme ligands reported in 1994 for the hydrogenation of acetamido cinnamic acid ( Rh-dendritic dppe ligang). . [46] Togni et al.[46] The excellent selectivity of the hydrogenation of cyclopentadiene to cyclopentene is remarkable. Another remarkable feature of this system is that the hydrogenation of 1. which favorably compares with supported catalysts. The metallodendrimer was less active than Pd/C and Pd/Al2O3. Moreover. There was a slight decrease in turnover frequencies upon growth of the RhI46 dendrimer. Rationalization of all these features would be speculative.Unique Design Tools for the Synthesis and Design of Dendrimers … 257 Kakkar’s group reported on an interesting organophosphine dendrimers with phosphorus atoms at the focal points (Figure 4). examined the selective hydrogenation of conjugated dienes to monoenes using an atmospheric pressure of H2 at 25 °C by the dendritic catalyst DAB-dendr[N(CH2PPh2)2PdCl2]16 prepared by reaction of Reetz’s dendritic phosphine (vide infra) with [PdCl2(PhCN)2].8%).[45] Mizugaki et al. but it seems that the active metallic sites are well accessible on the surface of the heterogeneous catalyst. THF). 20 bar H2. the dendritic catalyst can be separated from the reaction mixture using a nanofiltration membrane. The metallodendrimers containing [RhCl(η4-1. 12-.[45] The divergent construction involved reaction of (CH3)3SiNEt2 with P{(CH2)3OH}3 followed by sequential reactions of the dendrimer with these two reagents successively up to the P46 dendrimer. heterogeneization renders the system efficient. The catalytic activity (turnover number about 200 molprod (molcat)-1 and turnover frequency about 400 molprod (molcat)-1 h-1) was found to be similar to that of the monometallic complex. but these heterogeneous catalysts are not selective contrary to the dendritic catalyst.[47] These ferrocenylphosphine-rhodium(I) dendrimers catalyze the hydrogenation of dimethylitaconate (1) affording the desired product 2 (Scheme 2) with an enantioselectivity (ee) of 98%. The dendritic BINAP-Ru catalysts showed slightly higher enantioselectivity (ee = 92. After one such cycle of hydrogenation using the Rh46 dendritic catalyst. and 16-branch dendrimers with ferrocenyldiphosphine ligands and also synthesized the corresponding rhodium(I) complexes (Figure 5). this reaction was very efficient in ethanol in which the dendritic catalyst was not soluble whereas it was slow in DMF in which it was soluble.3-cyclooctadiene by the same dendritic-PdCl2 complex occurred with much higher rates than by the monometallic catalyst. Thus. Interestingly. decorated 8-. the organic product was extracted into pentane and the Rh46 dendrimer was recrystallized from THF/hexane mixtures and reused with only 5% decrease in conversion. The catalyst could be precipitated at the end of the reaction and then reused three times without loss of activity or enantioselectivity. The dendritic catalyst was easily recovered from reaction mixtures by centrifugation and reused without much loss of activity.[47] The Fan and Chan groups reported a series of dendritic BINAP ligands with Fréchet-type polyether wedges and their ruthenium complexes as catalysts in asymmetric hydrogenation of 2-[p-(2-methylpropyl)phenyl]acrylic acid in methanol-toluene (1:1. v/v) at 50 °C. which compares with the ee of 99% obtained for the monomeric Josiphos catalyst. The catalytic activity was higher than that of the corresponding monomer [PdCl2{PhN(CH2-PPh2)2}] and the polystyrene-bound catalyst. 30 min.5-C8H12)]2 and were shown to catalyze the hydrogenation of 1-decene in a 1:200 metal-to-substrate ratio (25 °C.6% with 100% conversion in 20 h) than Ru-BINAP (ee = 89.5-C8H12)PR3] moieties were best synthesized by reactions of these phosphorus dendrimers with [Rh(μ-Cl) (η4-1.[48] . El-Shehawy Figure 5.258 Ashraf A. Hydrogenation of dimethylitaconate. Example for Tongi dendrimers with optically active ferrocenyldiphosphine ligands.[49] Schematic illustration for the preparation of dendrimer-encapsulated bimetallic nanoparticles is represented in Scheme 3. PAMAM-OH) has been reported by Rhee et al. the first effort for the preparation of Pd-Rh bimetallic nanoparticles in the presence of poly(amidoamine) dendrimers with surface hydroxyl groups (fourth generation. . O O O O Chiral dendritic catalyst H2 O O O O 1 Scheme 2. (ee = 98%) 2 In an interesting approach. . The dendrimer-encapsulated Pd–Rh bimetallic nanoparticles were applied as catalyst to the partial hydrogenation of 1. however. the dendrimer-encapsulated nanoparticles are confined primarily by steric effects and therefore a substantial fraction of their surface is unpassivated and available for reactant to access in catalytic reactions. It was found that the reaction performance was as good as that of the fresh one. the highest activity was achieved with a Pd/Rh ratio of 1/2 in Pd–Rh system as shown in Figure 6. The cyclooctene selectivity at the complete conversion of 1. As shown in Figure 6. In order to confirm the feasibility of catalyst recycling. Schematic diagram for the preparation of dendrimer encapsulated Pd-Rh bimetallic nanoparticles.[49] Different from the conventional polymer stabilized nanoparticles.3-cyclooctadiene in ethanol/water mixture (v/v = 4/1). that there exist apparent differences between two systems.Unique Design Tools for the Synthesis and Design of Dendrimers … 259 Scheme 3.3-cyclooctadiene was higher than 99%. the dendrimer-encapsulated Pd–Rh bimetallic nanoparticles were found to be effective in the hydrogenation reaction. It is worth noting. which is as high as that of the palladium or rhodium nanoparticle catalyst. While bimetallic nanoparticles with Pd content of 80% showed the highest activity in the case of Pt-Pd. after a reaction was completed. the catalyst was reused. This indicates that the dendrimerencapsulated Pd–Rh bimetallic catalyst can be recycled and reused without a significant loss of its catalytic activity. The relationship between the size/generation of the dendrimer and its catalytic properties was established in the asymmetric hydrogenation of Zmethyl-α-acetamidocinammate and dimethylitaconate.3-cyclooctadiene.[50] Metallation of the multi-site phosphines with [Rh(COD)2][BF4]cleanly yielded the cationic rhododendrimers containing up to 32 metal centers (for the fourth generation species). an efficient strategy for the backbone functionalization of a tripodal phosphine ligand which allows its attachment to carbosilane dendritic supports has been developed by Gad et al. Dependance of the catalytic activity of dendrimers encapsulated Pd-Rh bimetallic nanoparticles on its composition in the partial hydrogenation of 1.4-bis(diphenylphosphino)pyrrolidine) with zeroth fourth (EDC)/1generation PPI using ethyl-N. selectively yielding the desired metallated dendrimers. Maarseveena et al. have been reported on the synthesis of a series of chiral phosphine functionalized poly(propyleneimine) (PPI) dendrimers by the reaction of carboxyl-linked C2chiral pyrphos ligand (pyrphos=3. Moreover.N-dimethylaminopropylcarbodiimide hydroxybenzotriazol as a coupling reagent. El-Shehawy Figure 6. The chiral ligands 5 and 7 were prepared as shown in Schemes 4 and 5. A decrease in both activity and selectivity of the synthesized rhododendrimers dendrimers was clearly observed on going to the higher generations.[51] These dendrimers were metallated with four and eight molar equivalents of [Rh(COD)2][BF4] in CH2Cl2.260 Ashraf A. have been reported on the functionalization of the axially chiral BICOL backbone with two third generation carbosilane dendritic wedges and further elaborated to a phosphoramidite ligand. Gade et al. Comparative catalytic hydrogenation of styrene and 1-hexene using the metallodendrimers showed that the fixation to the low generation dendrimers did not alter the catalytic hydrogenation properties of the catalysts.[52] . . R = J (R)-BINOL) 4. i) MeI. Synthesis of dendritic chiral ligand 7. Synthesis of physphoramidite ligand 5 from (R)-BINOL.Unique Design Tools for the Synthesis and Design of Dendrimers … 261 H N OR OR N H CH3 N . Scheme 5. R = TBS TBSL. NaH ii) TBAF iii) HMPT (95%) N CH3 CH3 O P N O CH3 3. Et3N (100%) (R)-5 Scheme 4. 5 2. in 2.0 2.2 4. Typically.0 2.5 h. For comparison. which are better than that obtained . All catalysts gave high enantioselectivities (up to 97.9% ee). The catalytic behaviour of the dendritic analogue 5 was similar. This shows the ability of the bicarbazole skeleton to induce high enantioselectivity. S Table 1. High enantioselectivities (up to 95% ee) were obtained when these monodentate ligands were applied in the rhodium-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate. When a ligand to rhodium ratio of 2. This shows a reasonable constant of formation of the product compared to the non-dendritic catalyst. Asymmetric hydrogenation of methyl-2-acemtamidocinnamate 8.262 Ashraf A. product 8 was obtained quantitatively with an enantiomeric excess of 95% (entry 4).[54] The rhodium-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate was first used as the model reaction to study the catalytic behavior of the dendritic ligands 10 and 11.2 3. El-Shehawy The rhodium-catalyzed asymmetric hydrogenation of methyl 2-acetamidocinnamate 8 was used as the model reaction to study the catalytic behaviour of the new ligands (R)-5 and (R)-7 (Scheme 6 and Table 1). Rh(COD)2BF4 (1 mol%) (R)-Ligand COOMe 8 H2 (5 bar) CH2Cl2.5 Conv.[52. Entry 1 2 3 4 5 6 a) b) Ligand Mono Phosph Mono Phosph Ratio L/Rh 2. The rhodium catalysts were prepared in situ by reaction of 2 equiv of the appropriate dendrimer ligands with [Rh(COD)2][BF4]in dichloromethane at room temperature.0 2.53] Fan and co-workers have been reported on the synthesis of a class of dendritic monodentate phosphoramidite ligands through substitution of the dimethylamino moiety in MonoPhos by the Fréchet-type dendritic wedge and their application in the asymmetric hydrogenation of α-dehydroamino acid esters and dimethylitaconate. room temp.2 2. a model compound of a small molecule 11 was also synthesized (Figure 7). the reactions were carried out at room temperature in dichloromethane as the solvent. the enantioselectivity induced by the rhodium complex based on ligand 3 (entry 3) was 93% (at full conversion). AcHN 9 COOMe AcHN Scheme 6.5 2.5 2. Determined by chiral HPCL (Diacel OD. The dendritic chiral ligands 10a-c were prepared in moderate yields.2 3.2 t (h) 2. heptanes-isporpanol=9:1) It is worth to mention that the Leeuwen group has examined the activity of Rh complexes of the dppf-type dendritic ligands in the hydrogenation of dimethylitaconate in a continuousflow membrane reactor. (%)a 100 0 100 100 100 ~30 ee (%)b 95 --93 95 95 90 5 7 7 7 Determined by 1H NMR.2 was used. 56] O O O O O O Ph N P O O O P O N n 11 10a. Dend-{CH2PPhR}n (R=2-biphenylyl or 9-phenanthryl) were prepared. n= 2) Figure 7. Hydrogenation of substrates with electron donating and withdrawing meta.Unique Design Tools for the Synthesis and Design of Dendrimers … 263 from Mono-Phos 11 (95%). Hydrogenation of dimethylitaconate also gave excellent enantioselectivities. 10c. 10b.55] These results indicated that the size of the dendritic substituents on the nitrogen atom would not result in any negative effect on the selectivity.[54.or parasubstituents on the phenyl group gave slightly higher ee values as compared to the orthosubstituted substrates. which are better than those of Mono-Phos). Carbosilane dendrimers (12-14.9 ee) were also achieved in all cases.[54.[57] The rhododendrimers Dend-{CH2PPhR(RhCl(COD))}n were cleanly obtained by reacting . which is in contrast to the results obtained with the corresponding small monodentate phosphoramidite ligands bearing different substituents on the nitrogen atom.[54. The same authors applied the same dendritic catalysts to the hydrogenation of other αdehydroamino acid ester substrates. Figure 8) containing P-stereogenic monophosphines as terminal groups. (n= 1). (n= 0).55] Figure 8.[54] Excellent enantioselectivities (up to 97. It was noted that the dendritic catalysts showed slightly higher enantioselectivities for all ortho-substituted substrates than those obtained from the monomer ligand 11. which are better or comparable to those obtained from Mono-Phos 11. 264 Ashraf A. El-Shehawy [RhCl(COD)]2 with the corresponding dendrimer in CH2Cl2 at room temperature. Recrystallization in CH2Cl2/diethyl ether gave the targeted rhododendrimers as yellow solids in good yields. They are soluble in most common organic solvents and were characterized by elemental analyses, 1H, 13C and 31P NMR spectroscopy, and ES mass spectrometry. The catalytic properties of the rhodium dendrimers were tested in the hydrogenation of dimethylitaconate. The model chiral compounds, (CH3)3Si{CH2PPhR(RhCl(COD))} and (CH3)3Si{CH2PPhR(RuCl2(p-cymene))}, were prepared in order to detect potential dendritic effects. All compounds were found to be active in the catalytic conditions tested, but low or null ee were found.[57] Fan et al have been recently designed and synthesized a new kind of dendritic pyrphos ligands bearing alkyl chains at the periphery for the Rh-catalyzed asymmetric hydrogenation of dehydroamino acids.[58] The new series of dendritic ligands with a chiral diphosphine located at the focal point have been synthesized through coupling of (R,R)-3,4bis(biphenylphosphino)pyrrolidine (pyrphos) with peripherally alkyl-functionalized benzoic acid dendrons (Scheme 7). H3C H2C H3C H2C n O COOH O H3C H2C n nO O H3C PPh2 H3C H2 C H2C O n O n C N PPh2 PPh2 H3 C H 2C O n + PPh2 HN (i) 15C-G1, n = 9 16C-G1, n = 15 9 H3C H2C 9 O H 3C H3C H2C O COOH H2C 9 O H 3C H 2C 9 O O 9 O O O O C N PPh2 PPh2 H3C H 2C + PPh2 HN PPh2 (i) H3C H2C 9 H3C H2C 9 O O H3C H2C 9 O O O H 3C H 2C H3C 9 O 9 H3C H2C O 9 O 9 H2C (i) DCC, DMAP, CH2Cl2, r.t. H3C H2C 17C-G2 Scheme 7. Synthesis of chiral deneritic pyprophos lignads. With these chiral dendritic catalysts, the asymmetric hydrogenation of acetamidocinnamic acid (18) as a standard reference system for comparing their catalytic performance (Scheme 8).[58] Scheme 8. Unique Design Tools for the Synthesis and Design of Dendrimers … 265 As it was expected, the number and length of the alkyl end groups of the dendritic wedges influenced the reaction performance and the results depended on the solubility of the dendrimer in solvent. Full conversion and high enantioselectivity (up to 95.6% ee) for the first generation dendrimer ligand 15C-G1 was observed, which are similar to those previously reported for the soluble polymer-supported catalyst (95.5% ee). Interestingly, full conversion and high enantioselectivity (up to 97.8% ee) were observed in case of using dendrimer ligand 17C-G2.[58,59] It was found that these dendrimer-based catalysts with alkyl tailed at the periphery preferred to dissolve in a non-polar solvent system. In the case of the second-generation dendritic ligand 17C-G2, more than 99% of its Rh complex could be extracted to the nonpolar cyclohexane phase in a methanol/cyclohexane (2.0% H2O) biphasic system. The cyclohexane layer, which contained the catalyst 17C-G2-Rh(I), was separated and reused in the next run of reaction. The recovered catalyst was reused five times with similar enantioselectivity, albeit decreased activity until the fourth cycle (Table 2, entry 4).[58,60] Table 2. Recycling of the catalyst 17c-G2-RH (I) in the asymmetric hydrogenation of acetamidocinnamic acid 18. Entry 1 2 3 4 5 Cycle First Second Third Fourth Fifth Conv. (%) 100 99 97 83 56 ee (%) 97.0 97.1 97.0 96.8 95.5 6.1.2. Asymmetric Transfer Hydrogenation to Ketones and Imines The chiral diamine core was discovered by Noyori for the catalysis of asymmetric transfer hydrogenation of acetophenone which [RuCl2(η6-cymene)]2 is the Ru source and is available on the kilogram scale.[61] The dendrimers rather favorably compare with the parent nondendritic catalyst in terms of activity, and the enantioselectivity was retained. It was remarkable that, upon recycling the dendritic catalyst, the enantioselectivity was retained while the activity only decreased slightly. Deng et al. have been reported on the synthesis of multiple dendritic ligands 20-22 based on (R,R)-1,2-diphenylethylenediamine in a convergent approach (see Figure 9).[62] Their ruthenium complexes prepared in situ had good solubility in the reaction medium (azeotrope of formic acid and triethylamine). Initial experiments were conducted to test the catalytic activity of ruthenium(II) complexes of the dendritic ligands in the asymmetric transfer hydrogenation reaction of acetophenone which was used as the model substrate and the azeotrope of formic acid and triethylamine as the hydrogen source. Ru(II) complexes of (R,R)-TsDPEN (23) and (R,R)-N-(4-acetylaminophenylsulfonyl)-1,2diphenylethylenediamine (24) were selected as monomeric catalysts for comparison.[62] It was found that the macromolecular catalysts showed no significant difference in activity and enantioselectivity in the asymmetric transfer hydrogenation of acetophenone as 266 Ashraf A. El-Shehawy compared with the monomeric catalysts 23 and 24. Good retention of catalytic activity and high enantioselectivity were observed in these dendritic catalysis. However, the glycine spacer had mild negative effects on the catalytic activity (entries 3 vs 4; Table 3). O C O R O O Ph S NH Ph NH2 4 20. R = NH 21. R = NHCOCH2CHNH2 22. R = H Figure 9. Table 3. Comparison of Dendritic and Monomeric Catalysts in Asymmetic Transfer Hydrogenation of Acetophone a. a Reactions were conducted at 28oC for 20h. S/C=100. Conversions were determined by GC. c The average TOFs were calculated over the 5h reaction time. d Determined by GC with a Chrompack CP Chirasil-dex column (25m x 0.25mm). b Unique Design Tools for the Synthesis and Design of Dendrimers … 267 For exploring the scope and limitations of this reaction catalyzed by the dendritic catalysts, a variety of ketones and imines (see Figure 10) were applied in the asymmetric transfer hydrogenation with HCOOH-NEt3.[62] In general, excellent conversions with quantitative yields and for some cases a slightly higher enantioselectivities (up to 98.7% ee) were obtained using the dendritic catalysts. Considering the high local catalyst concentrations at the periphery, diones were tested for the possible synergic reactivity between catalytic units at the surface, while no apparent differences were noted.[62] O O O n O S O N O S N O O Ph P N Ph a. R = o-F b. R = p-F c. R = o-Cl d. R = o-Br e. R = p-Br a. n = 1 b. n = 4 R a. R = Bn b. R = But Figure 10. Scheme 9. Synthesis of dendronized poly(BINAP)s. Fan et al. reported on the synthesis of a new kind of dendronized polymeric chiral BINAP ligands and applied to the Ru-catalyzed asymmetric hydrogenation of simple aryl ketones and 2-arylacrylic acids. The dendronized poly(BINAP) ligands were synthesized as shown in Scheme 9.[63] These dendronized poly(Ru-BINAP) catalysts exhibited high catalytic activity and enantioselectivity, very similar to those obtained with the corresponding parent Ru(BINAP) and the Ru(BINAP)-cored dendrimers. It was found that the pendant dendrons 268 Ashraf A. El-Shehawy had a major impact on the solubility and the catalytic properties of the polymeric ligands. These polymeric catalysts could be easily recovered from the reaction solution by using solvent precipitation, and the reused catalyst showed no loss of activity or enantioselectivity.[63] The catalytic efficiency of the dendronized poly(Ru-BINAP) catalytic system was further demonstrated in the asymmetric hydrogenation of 2-arylacrylic acids.[63] The Ru catalyst was prepared by mixing [Ru(benzene) Cl2]2 and the appropriate polymeric ligand in situ in hot DMF. High enantioselectivities were obtained in the asymmetric hydrogenation of 2-[p(2-methylpropyl)phenyl]acrylic acid and 2-phenylacrylic acid (82-83% ee), which were comparable to those obtained with Ru(BINAP) under otherwise identical reaction conditions. It was found that the size of the pendant dendrons also slightly influenced the enantioselectivity of the polymeric catalysts.[63] It is importantly to note that the Ru catalyst with the third generation pendant dendrons was used for the recycling experiments. Upon completion of the reaction, methanol was added to the reaction mixture and the catalyst was quantitatively precipitated and recovered via filtration. The recovered catalyst was reused for at least three cycles in the asymmetric hydrogenation of 2-methylacetophenone with similar enantioselectivity (~92% ee).[63] Hydrophobic Fréchet-type dendritic chiral 1,2-diaminocyclohexane-Rh(III) complexes have been prepared and applied in the asymmetric transfer hydrogenation of ketones in water using HCOONa as hydrogen source.[64] The core-functionalized dendritic ligands 29a-d based on chiral 1,2-diaminocyclohexane (DACH) were smoothly prepared as illustrated in Scheme 10. The dendritic structures could be established through MS techniques (ESI HRMS or MALDITOFMS). Scheme 10. Synthesis of dendritic DACH ligands. With the desired chiral dendritic ligands 29a-d, the catalytic activity and enantioselectivity of their ruthenium or rhodium complexes were studied via the transfer hydrogenation of acetophenone, and also compared with the monomeric TsDACH-metal complex.[63,64] The transfer hydrogenation reactions was conducted in three different conditions for detailed comparison of the dendritic catalysis at 1 mol% catalyst loading: (a) [RuCl2(cymene)]2 as the metal precursor in DCM solution, the azeotrope of HCOOH–NEt3 as Unique Design Tools for the Synthesis and Design of Dendrimers … 269 the hydrogen source at 28 ◦C; (b) [RuCl2(cymene)]2 as the metal precursor in aqueous solution, HCOONa as the hydrogen source at 35 ◦C; (c) [RhCp*Cl2]2 as the metal precursor in aqueous solution, HCOONa as the hydrogen source at 40 ◦C. Although quite different results were obtained under the above-mentioned three reaction conditions, in general, good retention of high enantioselectivity was observed for all dendritic catalysts as compared to the monomeric metal TsDACH-metal complex. It is worth to mention that the reduction of acetophenone took place smoothly at 0.1 mol% of 29b–Rh(III), furnishing a >99% conversion with 94% ee in 4 h.[64] The recyclability of these dendritic catalysts was then tested via the solvent precipitation method. The second generation dendritic 29b–Rh(III) complex at 1 mol% loading was employed in the transfer hydrogenation of acetophenone, as the example. The recycling use of dendritic 29b-Rh(III) catalyst was quite successful and excellent conversion (97%) and enantioselectivity (95% ee) were obtained even in the sixth run with some extension of the reaction time.[64] Subsequently, the above-mentioned protocol was extended to a range of aromatic, heteroaromatic and functionalized ketones (Figure 11), aiming to determine the potential applicability of the dendritic catalytic system in the asymmetric transfer hydrogenation in water. Excellent conversions (up to >99%) and high enantioselectivities (up to 97% ee) could be obtained.[64] Figure 11. Structures of various ketones. Deng et al. have been reported on the synthesis of tunable dendritic N-monosulfonyl ligands via direct N-monosulfonylization of the chiral dendritic vicinal diamines. The chiral dendritic N-arylsulfonyldiamine ligands (R,R)- and (S,S)-30 that are shown in Figure 12 were prepared in good to high yields (65-85%). The application of these dendritic ligands in the asymmetric transfer hydrogenation of ketones was investigated. For comparison, a monomeric ligand, (R,R)-31 was also prepared.[65] The asymmetric transfer hydrogenation was first studied using acetophenone as the model substrate. Compared to the complexes of monomeric ligand (R,R)-31, as well as TsDPEN, a slightly enhanced reactivity was observed for the dendritic catalysts, Ru[(R,R)-30] with similar enantioselectivities which are more active than those dendritic catalysts derived from amino-functionalized vicinal diamine (the TOF values are less than 12). However, when the third generation catalyst of Ru[(R,R)-30] was used, the reactivity had a notable drop in only 75% conversion (TOF value is 4.3) along with a slight decrease of enantioselectivity with the same reaction time. In general, the hydrogenated product was obtained with high yields (conversion was >99%) and high enantioselectivities up to 97.5% ee. Interestingly, the second generation catalyst of Ru[(R,R)30] could be recovered by precipitation with an addition of methanol after removed of DCM under reduced pressure and reused four times with slightly higher enantioselectivities (97.5, 97.2, 97.5 and 97.0% ee vs 96.1% ee).[65] 270 Ashraf A. El-Shehawy Several aliphatic and aromatic ketones as substrates were also examined in the asymmetric hydrogenation reaction using the dendritic catalysts (R,R)- and (S,S)-30. In general, the conversions of ketones and enantioselectivities of the reduced products did not obviously change when using dendritic (R,R)- and/or (S,S)-30 as a ligand compared to the monomeric ligand (R,R)-31 and TsDPEN. The above-mentioned study showed an increase of enantioselectivities in the asymmetric reduction could be achieved by fine tuning of the coordinating amino group NH2 of chiral 1,2-diamines.[65] O O R1HN * R2HN * O O n MeO OMe O NHSO2C6H4-p-CH3 O H2N n (R,R)-31 (R,R)- and (S,S)-30 Figure 12. Fan and Shuai have been reported on the synthesis of a series of new chiral dendritic BIPHEP ligands and their applications in the Ru-catalyzed asymmetric hydrogenation of βketoesters were investigated.[66] The authors chose enantiopure MeO-BIPHEP as the starting compound to make the dendritic BIPHEP ligands 35a-c. The synthetic procedure is outlined in Scheme 11. O O Br O O n n O O O O n O HO HO PPh2 PPh2 a 95 % HO HO PPh2 PPh2 O 33 b PPh2 PPh2 O c (R)-35 n=1, 35a, 84% n=2, 35b, 99% n=3, 35c, 99% 32 O O 32 d 50% PhCH2O PhCH2O PPh2 PPh2 O e 70% PhCH2O PhCH2O PPh2 PPh2 n=1, 34a, 55% n=2, 34b, 50% n=3, 34c, 60% 36 37 Scheme 11. Synthesis of dendritic BIPHEP Regents and conditions. (a) H2O2 (35%), CH3OH 2h at r.t; (b) 33, K2CO3, acetone, reflux; (c) NEt3/NBu3, toluene, reflux; (d) benzl bromide, K2CO3, acetone, reflux. Unique Design Tools for the Synthesis and Design of Dendrimers … 271 In order to evaluate the catalytic efficiency of these dendritic ligands and the influence of the dendritic wedges on the enantioselectivity of a given reaction, the well-studied asymmetric hydrogenation of β-ketoesters was selected as the standard reactions (Scheme 12). The Ru-catalyst was prepared by mixing [Ru(benzene)Cl2]2 and the proper dendrimer ligand in situ in hot DMF. The reaction was carried out in a CH2Cl2-ethanol mixture as the solvent under 40 atm of H2 pressure at 60 ◦C for 24 h. For comparison, the model ligand 37 was performed under the same reaction conditions.[66] O R1 O OR2 Dendritic Ru(BIPHEP), H2 CH2Cl2/ C2H5OH (1:1) OH O R1 * OR2 Scheme 12. Asymmetic hydrogenation of B-ketoester catalyzed by dendritic Ru (BIP HEP) catalysts. While all dendritic catalysts showed similar reactivity, the enantioselectivity varied dramatically with increase in generation from 1 to 3. For example, methyl 3-oxo-3phenylpropanoate was reduced with ca. 93.1% ee using the model small molecule Ru(37) catalyst. The enantioselectivity decreased to 92.0% ee with the first generation Ru(35a) catalyst and reached a minimum of 86.6% ee with the second generation Ru(35b) catalyst. Unexpectedly, with further increase of generation to 3, enantioselectivity increased slightly to 91.3% ee. This result indicated that similar catalytically active Ru-complex of Ru(35c) was formed under the reaction conditions despite the bulky dendritic substituents. This general trend was found to be true for all substrates used in this study.[66] It has been recently reported that the asymmetric hydrogenation of quinolines catalyzed by chiral dendritic catalysts derived from BINAP gave the corresponding products with high enantioselectivities (up to 93%), excellent catalytic activities (TOF up to 3450 h-1), and productivities (TON up to 43 000).[67] Fréchet-type polyaryl ether dendrons were chosen for this study owing to their chemical inertness and inability to coordinate iridium. The synthetic pathway and structures of the dendritic ligands are shown in Scheme 13. Scheme 13. Synthesis and Structures of Dendritic GnDenBINAP Ligands. 272 Ashraf A. El-Shehawy The effects of the solvents, temperature, hydrogen pressure, and additive on the activity and enantioselectivity were investigated by using the second-generation dendrimer catalyst, which was generated in situ from G2DenBINAP and [Ir(COD)Cl]2 (Table 4). A series of organic solvents were tested, and THF was found to be the best choice in terms of both conversion and enantioselectivity (entries 1-5). The enantioselectivity of the reaction was slightly increased at low temperature, but the reaction could be completed at prolonged time (entry 8). Notably, low conversion and enantioselectivity were observed under both higher and lower hydrogen pressure (entries 9 and 10). The reaction could not proceed without iodine as an additive (entry 13).[67] Table 4. Asymmetric Hydrogenation of Quinaldine (38a) Catalyzed by Dendritic Ir (G2DenBINAP) Catalysta. a Reaction conditions: 0.25 mmol of quinaldine 38a in 1.25mL of solvent, 0.5 mol% of [Ir(COD)C1]2, 1.1.mol % of (S)-G2DenBINAP, I2/catalyst = 10 (mol/mol), 45 atm H2, 15-20oC. b Determined 1H NMR analysis of the crude product. c . Determined by HPCL anaylysis with Chirapak OJ-H column. The predominated product was in the Sconfiguration. d Reaction temperature = 50oC e Reaction temperature = 0oC. f H2 = 100 atm. g H2 = 10 at, h I2/catalyst = 1 (mol/mol). i I2 = 0 mol %. The applications of the dendritic catalyst in the asymmetric hydrogenation of other 2substituted quinoline derivatives using G2DenBINAP as the ligand were further investigated Unique Design Tools for the Synthesis and Design of Dendrimers … 273 (Table 5). In general, all substituted quinolines studied were hydrogenated with good enantioselectivities and conversions.[67] The reaction was found to be relatively insensitive to the length of the 2-alkylated side chain of quinolines, and high enantioselectivities and good yields have been consistently obtained (entries 1-3). Notably, under low catalyst loading, the reactions performed well, affording similar enantioselectivities, albeit low catalytic activities (entries 1-7). The authors then investigated the recyclability. G3DenBINAP-Ir-catalyzed asymmetric hydrogenation of 38a was chosen as the standard reaction. Upon the completion of the reaction, the catalyst was quantitatively precipitated by the addition of hexane and reused at least six times with similar enantioselectivities but at the expense of relatively low catalytic activities.[67] Tabel 5. Catalytic Asymmetric Hydrogenation of Quinoline Derrivativesa. a Reaction conditions: 0.25 mmol of substrate in 1.25 mL of THF 0.25 mol% of Ir(G2DenBINAP) catalyst. 5 mol% of I2, 20-25oC, 1.5h. b Determined by 1H NMR analysis of the crude product. c Determined by HPCL analysis with Chirapak OJ-H (38a-c, 28i and 38j). AS-H 938d and 38e) and OD-H (38f-h and 38k) columns. d The Absolute configuration is assigned by comparison of the HPCL retention time with those reported in the literature data. e Data in brackets were obtained by usint 0.01% catalyst under the following conditions: 2.5 mmol of substrate in 5 mL of THF, 1.125 mol% of I2, 20-25oC, h. f Reaction time =36h. n = 0. m = 4 Gx is the generation x of the carbosilane dendimer. x = 1. n = 1. reagents (i) HSiMe2CH2CI2 [Pt].g. m = 12 42. x = 0. n = 0. x = 0. x = 1. m = 4 44. m =36 43. i. The Reek and van Leeuwen group synthesized diphenylphosphine-functionalized carbosilane dendrimers Si{(CH2)nSi(CH3)2(CH2PPh2)}4 (n=2. during the last decade. 3. n = 1. n = 0. mostly based on rhodium and cobalt complexes. n = 1. m = 36 ii Gx n Si PPh2 m Gx iii n Si Cl m v Gx n m Gx n Cl Si Cl v m Gx n Si PPh2 PPh2 m 52. and hydrogen into linear or branched aldehydes (Scheme 14). generation 1. n = 1. n = 0. x = 1. x = 0. (ii) HSiMeCI2. m = 4 41. n = 1. m = 12 45. The catalyst was prepared in situ by mixing (acetylacetonato)dicarbonylrhodium(I) and the dendrimeric ligand under H2/CO pressure of 20 bar. However. n = 0. El-Shehawy 6. These chiral ligands were used for the rhodium-catalyzed hydroformylation of 1-octene. n = 1. m = 36 40. (iii) HSiMeCI2 [Pt]. m = 12 51.[68] The homogeneous catalysis. (v) Ph2PCH2Li-TEMEDA. m = 4 47. x = 2. x = 0. m = 4 55. n = 0.274 Ashraf A. Hydroformylation The hydroformylation reaction extensively used in research and industry. e. m = 12 48. x = 0.CH2PPh2 (57) were used for comparison. (iv) Ph2PK.70] Gx i m n Gx n Si Cl m iv 46.2. n = 0. there has been growing interest in developing various catalytic systems for the reaction to successfully recycle the expensive catalytic complexes. m = 12 54.e. carbon monoxide. m =36 49. n = 0.[69-71] Neither isomerization of 1-octene nor hydrogenation to alkanes and alcohols was observed during the catalytic reactions. The dendrimeric structure. These diphenylphosphine terminated carbosilane dendrimers were used as ligands in the rhodium catalyzed hydroformylation of 1-octene.[69. x = 2. The selectivity for the linear and branched aldehydes of the dendrimeric systems is the same as that of the model systems 56 and 57 (Table 6).[69] The diphenylphosphine functionalized carbosilane dendrimers with both monodentate and bidentate end groups were synthesized by hydrosilylation of the various generations of carbosilane dendrimers with chlorodimethylsilane or dichloromethylsilane followed by a reaction with lithium methyldiphenylphosphine-TMEDA (Scheme 15). Synthesis of diphenylphospine functionalized carbosilane dendrimers. 3. x = 1. R + CO + H2 Catalyst R CHO CHO + R Scheme 14. converts terminal olefins. is the predominant approach to this process. x = 2. x = 2. Model compounds (H3C)3SiCH2PPh2 (56) and (H3C)2Si. the different generations of dendrimers with .. n = 1. G0 = tetraallylsilane or tetravinylsilane Scheme 15. n = 1. 2). Hydroformylation reaction. x = 1. m = 4 53. m = 4 50. x = 1. x = 0. generations 1-3) and Si{(CH2)nSi(CH3)(CH2PPh2)2}4 (n=2. [1-octene] =638mM in toluene. For this purpose.5. Gong et al. conversion after 1h. a T = 80oC.[74] Cole-Hamilton’s group reported on the synthesis of dendrimers based on polyhedral oligomeric silsesquioxanes cores with 16 PPh2 arms (Figure 13) that give much higher linear selectivities (14:1) than their small molecule analogues (3-4:1) in the hydroformylation of cyclooct-1-ene catalyzed by the RhI complex. synthesized four water-soluble dendritic phosphonated ligands based on PAMAM dendrimers of generation 3 (32 end groups) with the hydrophilic amine or sulfonic acid group on the surface of the dendrimer. the PAMAM dendrimers were allowed to react with [Ph2P(CH2OH)2]Cl and 1. However. The RhI dendritic complexes were used as the catalysts in the two-phase hydroformylation of styrene and 1octene under mild reaction conditions (40 °C.[75-77] . It was pointed out that such catalysts could be separable by membrane separation techniques. modified Meijer’s 16-branch polypropylene imine dendrimer with chelating diphenylphosphine ligands. Results of rhodium catalysed hydroformylation of 1-octene using various dendrimeric ligandsa. [Rh] = 1mM. P/Rh = 2. has no influence on the selectivity of the reaction. This polyphosphine dendrimer formed complexes with various transition-metal groups such as PdMe2 or Rh(cod)BF4 (cod=1. which led to a 32-branch phosphine dendrimer.3-propane sultone. differences in reaction rates between the various dendrimeric ligands have been observed. a difference that is also observed for the model compounds (56 and 57).Unique Design Tools for the Synthesis and Design of Dendrimers … 275 monodentate and bidentate end groups. pco=pH2 =10 bar. 20 atm).[72.73] Hydroformylation of 1-octene with the RhI dendritic catalyst showed a turnover number comparable to that of the monomer.[72] Table 6. High catalytic activity for both styrene and 1-octene and high selectivity for the isoaromatic aldehyde were found.5-cyclooctadiene) which had catalytic properties.[69-71] Reetz et al. The dendrimers with bidentate end groups (14-16) give slower catalysts than the dendrimers with monodentate end groups (7-12). vinyl benzoate. O SiO2 O O H N O O N N H NH2 Si N i 2 2 O SiO2 O O Si N O H N O N N H N PPh2 PPh2 ii 2 2 O SiO2 O O Si N O H N O N N H N Ph2 P Rh(CO )Cl 2 PPh2 (i) HPPh2 and CH2O & (ii) [Rh(CO)2Cl]2 2 2 Scheme 16. Arya. Indeed. while this distance in the 5-10 Å range between arms (from molecular modeling).79] prepared a number of Rhbased supported dendritic catalysts and tested them in the hydroformylation of styrene. the phosphorus atoms are separated by five atoms including one silicium atom. 4-7 Å within one arm.. analogous metallodendrimers containing only one more CH2 unit between the Si and P atoms showed no special selectivity enhancement over the monometallic catalysts.[75-77] The cooperating groups of Alper. Cole-Hamilitons polyhedral silsesquioxane cores.276 Ashraf A. . This positive dendritic effect was explained by the steric crowding and small arm length inducing eight membered ring bidentate coordination that enhances the linear selectivity. and a number of other olefins.[78a] Figure 13. Preparation of silica-suported dendritic catalysts for hydrofrmyltion. i. Fluxionality within the complex was also suggested based on 31 P NMR studies.e. and Manzer[78. PAMAM dendrimers were converted into diphosphine ligands and further into Rh complexes (Scheme 16). vinyl acetate. El-Shehawy In this metallodendrimer. On silica. First. In this study. excellent regioselectivity (higher than that of the first two systems. relieved steric crowding and presumably led to more dendron-like structures and an increase in the metal catalyst loading. These catalytic systems showed even higher reactivity (enabling room-temperature hydroformylation). the 1.2-diaminoethane being substituted by 1. which could be recycled four times without a loss of activity. The third-and fourth-generation catalysts were only marginally active at room temperature. probably because of the lower . at 75 °C.[79c] Each monomer thus formed four propagation sites. The improvement for the third.. cannot be drawn because the report did not contain critical data about the metal loading on silica.[79b] The extension of the branch length. or 1. only the ligands and complexes of the zero to second generations could effectively be formed. it seems that the activity of the catalyst increased as a function of the generation.and third-generation derived catalysts were more active than the firstgeneration-derived one and could be recycled a number of times without a loss of activity.and fourth-generation catalysts was achieved through the elongation of the diamine fragment of the branching module of the PAMAM dendron. on each dendron were formed.12-diaminododecane. although exact conclusions regarding the change in activity per metal equivalent. The apparent turnover frequency is often affected by the initial amount of the catalyst.5-diaminobenzoic acid based peptide-like monomers were decorated with diphosphine chelate ligands and their Rh complexes. The best results were achieved for the fourth-generation catalyst based on diaminododecane. in this study and in subsequent reports from these groups. 1. Nevertheless. the functionalization and complexation of the third and fourth generations only occurred with extremely low efficiency. Moreover. even these catalysts were active.4diaminobutane.g.Unique Design Tools for the Synthesis and Design of Dendrimers … 277 Initially. respectively. The preparation of superior catalysts through changes in the design and generation of the dendritic template is remarkable.[78b] In the second-generation dendrons. and the biphosphine-rhodium complex was attached to the first-generation module. the reactivity and recyclability of the second generation-derived catalyst were notably better with some substrates (e. vinyl benzoate).and second-generation dendrons were constructed on polystyrene.[78a] The dendrons incorporating 3.and second-generation catalysts bearing 4 and 16 rhodium complexes. probably because of the very low metal loading on the silica. The length extension indeed resulted in additional improvement in the activity and recyclability of the catalysts. the outer layer modules did not carry metal and were used to isolate the catalytic site from the environment. the catalysts were compared with an equal amount of silica/polymer rather than metal. Regretfully. The catalysts demonstrated high activity and strong selectivity toward the branched product. The two aforementioned catalytic systems on polystyrene were further evolved into a dendritic catalyst with lysine-containing peptide-like modules. The second. An additional study explored the influence of the isolation of the catalyst environment on the polystyrene supported catalytic systems in the hydroformylation reaction was also investigated. Because of steric hindrance. this point cannot be unequivocally concluded because. as well as the existence and magnitude of the dendritic effect. The same cooperating groups also prepared polyamidodendrons on polystyrene. from the reported turnover rate measurements. This interesting dendritic effect again emphasizes the influence of the dendritic template architecture on the catalytic outcome. first. The hydroformylation reaction again demonstrated high activity associated with this type of design of the catalytic system.6-diaminohexane. Although the metal loading of the second-generation catalyst was lower than that of the first (because the number of metal atoms per dendron was equivalent for both). Hyedroformylation of olefins catalyzed by dendritic Rh (CO)2(PPh3)2 catalystsa. and outstanding recyclability. In this study. This catalytic system was successfully applied to the carbonylative ring expansion of aziridines. OCH 2 PPh2 PPh2 Ph2P H3CC OCH2 PPh2 CH2O O O C CH3 H3CC OCH2 O OCH 2 OCH OCH 2 3 Ph2P CH2O 58 59 3 PPh2 PPh2 2 3 Figure 14.[80] The Frechet’s polyether dendrimer instead of poly(propyleneimine) (PPI) or poly(amidoamine) (PAMAM) dendrimers was chosen as the backbone. the rhodium-catalyzed hydroformylation of olefins was chosen as the model reaction. El-Shehawy reaction temperature). As shown in Table 7. Figure 14. The catalysts were prepared in situ by mixing Rh(acac)(CO)2 and the dendritic ligand under a CO/H2 pressure of 20 bar. However.278 Ashraf A. Fan et al. the second and third generation catalysts gave low . 20bar(CO/H2 =1). b Selectivity of aldehyde was more than 99%.[80]. which is inert to almost all reactions. The results are summarized in Table 7. All of the obtained results clearly demonstrated the formation of monodispersed dendrimer functionalized with phosphines at the periphery. high reactivity and regioselectivity for the first generation dendrimer catalyst was observed with low catalyst loading. which was comparable to the parent catalyst (entries 1 and 2). have been reported on the synthesis of a new class of dendrimers functionalized with triphenylphosphines at the periphery by using convergent method (Figure 14).5m of olefin under the following reaction conditions: substrate/Rh =500:1. temperature =80oC: 2ml solvent. Styrene and 1-octene were chosen as the standard substrates. 60 Table 7. a Reactions were carried ot with 0. [83-85] They studied the increased influence of conformational rigidity as the generation number increases in poly(propyleneimine) dendrimers on the asymmetric addition of diethylzinc to benzaldehyde catalyzed by optically active amino alcohols (Scheme 17). In contrast.3. In comparison with those in toluene. albeit higher than that of the parent catalyst (entries 5-8).82] SBA-15 has been functionalized by two methods. and these dendritic catalysts have been tested for the addition of diethylzinc to benzaldehyde.Unique Design Tools for the Synthesis and Design of Dendrimers … 279 regioselectivity and significantly decreased conversion (entries 3 and 4). Thus.[81.1. regio-selectivity and stability of the catalyst by minimizing the leaching of the rhodium complex catalyst from the catalyst support to the liquid-phase media. the silanols outside the SBA-15 pores have been passivated to preclude the rhodium precursor to be tethered outside the channels.82] 6. This reaction is indeed an ideal test reaction for the induction of asymmetry by amino alcohol catalysts. The chemical yields and ee drop as the dendritic generation of the catalyst increases (ee drops from 36% for the monofunctional catalyst to the fifth-generation dendritic catalyst). hydroformylation of 1-octene gave the linear aldehyde as the main product. Therefore. O H + ZnEt2 2% Catalyst toluene / hexane * OH Scheme 17. In the passivation method. Reaction of diethylzinc with benzaldehyde using these dendritic catalysts led to a dramatic drop in enantiomeric excess.[80] Interestingly. The regioselectivity slightly decreased with increasing generation of the catalysts.3. Wilkinson’s catalyst (RhCl(PPh3)3) precursor has been tethered on these dendritic supports to produce heterogeneous catalysts for hydroformylation reaction of styrene. going from 11% to 0% for catalysts with 1-64 end groups. The profound generation effect was due to the insolubility of the higher generation catalyst in toluene. Dialkylzinc Addition to Unsaturated Substrates 6. With phosphine:rhodium ratio = 10:1. Diethylzinc addition to benzaldehyde. dichloromethane was chosen to be the reaction medium in order to sustain homogeneous reaction conditions for all generation catalysts.85] Optically active R-styrene oxide was also brought into reaction with the amine-functionalized poly(propyleneimine) dendrimer yielding mainly the secondary alcohol-secondary amine functionalities. The rhodium catalysts supported in the pore channels of this passivated SBA-15 show positive dendritic effects in enhancing the catalytic activity.[83. the .[81. similar regioselectivity was obtained for the dendritic systems and the parent catalyst (entries 9-12). Dialkylzinc Addition to Aldehydes Meijer and Peerlings reported the first catalytic studies with high-generation dendrimers. high conversion was obtained (entries 7 and 8). after PAMAM dendrimers have been successfully grown in SBA-15 mesoporous materials. Poly(propyleneimine) dendrimers have been modified with (R)-phenyloxirane and their corresponding N-methylated derivatives (Figure 15). [86] There was no detectable decrease of selectivity (98:2) up to the second generation. Rheiner and Seebach used dendritic Ti-TADDOLates with Fréchet-type branches up to the fourth generation (64 branches) in the enantioselective addition of Et2Zn to benzaldehyde. Figure 15.280 Ashraf A. This negative dendritic effect was attributed to an increase in steric hindrance of the end groups at the periphery of the dendrimer. resulting in an increased difficulty for all end groups to adopt their preferred conformation in order to catalyze the diethylzinc addition. The authors pointed out that there might be applications for special properties such as high molecular weight. good solubility. and spacing of central sites from cross-linked polymer matrixes. The presence of H-bonds greatly enhances this effect. Peerlijgs and Meijer’s poly (propylene imine) dendrimers modifield with ®-phenyloxirane for the catalytic asymmetric addition of diethylzinc to benzaldehyce. El-Shehawy dendritic effect is negative in both of these cases. and the rates hardly decreased up to the third generation. . Enantiomeric branches caused no change for stereoselectivity within experimental error. 3-dioxolane-4.[87. while all others do not swell as well after multiple reuse. It has been used for the enantioselective catalysis of nucleophilic addition of diethylzinc to aldehydes. The catalyst ligand core. The Ti(IV)-TADDOL dendritic polystyrene catalyst also has a much higher turnover rate than linear polystyrene analogues. Seebach and co-workers have been also synthesized a hexa-arm dendrimer and attached their ligand of C2 symmetry. (iv) the rate of reaction is the same with and without stirring using the beads of dendritic catalyst that has the shortest spacer filling the whole reaction volume under standard conditions. Seebach’s denddritic Ti-TADDOLates coordinated with Ti(IV) with Fre’chet-type branches (homogeneous and heterogeneous on polystyrene support) for the enantioselective addition of diethylzinc to benzaldehyde.[89. the authors found that the enantiomeric addition of diethylzinc to benzaldehyde proceeded .α.5-dimethanol) (Figure 17). the authors investigated the use of membrane reactors in these enantioselective catalytic reactions. TADDOL (α.88] The same authors further extended their studies to such dendritic catalysts with spacers of variable length and flexibility and found remarkable features: (i) while the enantioselectivity is above 9:1 with all polymers of low loading. used Fréchet’s dendrimers with styryl end groups to cross-link a catalyst to a polystyrene support.90] Moreover.[91] Figure 16. only the dendritic polymer gives rise to a constant selectivity of 98:2 in 20 sequential applications. Therefore. TALDOL.α′-tetraaryl-1. Using this chiral metallodendrimer. is coordinated to Ti(IV) (Figure 16). This means that diffusion of reactants and products to and from the active center is obtained. (ii) the catalytic performances drop with increasing the chain length of the spacers between the TADDOL core and polymer backbone.α′. and the Ti(OCHMe2) group at the periphery. (iii) the low-loaded dendritic catalyst beads with the shortest spacer keep their swelling properties high even after 20 runs.Unique Design Tools for the Synthesis and Design of Dendrimers … 281 Seebach et al. they synthesized TADDOL derived dendritic catalysts with a molecular weight high enough to be retained inside a membrane that is impermeable to the catalyst but permeable to reactants and products. High enantioselectivities were obtained for the addition of diethylzinc to aldehydes. in both cases.6′-tetrabromo-1. El-Shehawy with the same enantioselectivity (ee. Such aggregate is not formed in the case of the dendrimer due to the bulky and rigid dendritic arms. 89% ee).er attached to chiral TADDOL who related metallodendrimer with Ti(OCHMe2) group at the periphery..[92. i. Seebach’s hexa-arm dendro. High enantioselectivity in the presence of [Ti(O-i-Pr)4] was found for the dendrimer (100% conversion. 90% ee) as well as for BINOL (100% conversion.282 Ashraf A.[94] Both enantioselectivities of the dendrimer and BINOL are very low. had to be separated by column chromatography rather than by ultrafiltration methods.4′. monomeric. 97%) as the monomeric chiral catalyst. This dramatic difference is due to the fact that the zinc complex formed from the reaction with BINOL is likely to exist as aggregates in solution through intermolecular Zn-OZn bonds which should greatly reduce the Lewis-acid activity of the zinc center.6. The metallodendrimer.6% conversion in 24 h at room temperature) than (S)-BINOL (37% conversion under these conditions) and also generates the opposite enantiomeric product. yet the molecular models show that there is enough space allowing the substrate to approach the reaction center. The advantage of the dendrimer over BINOL is that it can be easily removed from the reaction mixture by precipitation with methanol.[94] The G-2 dendrimer catalyzed the asymmetric alkylation of benzaldehyde with diethylzinc with a much higher catalytic activity (98.[94] . Very interesting rigid dendrimers have been constructed by Pu’s group around an optically pure diacetate of 4.e.93] Figure 17. with a molecular weight of only 3833 Da. indicating that the catalytic center must be identical.1′-bi-2-naphthol (Figure 18). have been reported on the synthesis of two kinds of dendritic chiral BINOL ligands through the condensation reaction between 2.6.3'- . Fan et al.Unique Design Tools for the Synthesis and Design of Dendrimers … t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu 283 t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu t-Bu Figure 18.6’tetrabromo-1. O n O O OH OH O OH OH H N O O H N O n O O N OH OH N O O O n O O O O n 64 (n=0-3) 65 (n=0-3) O n 66 (n=0-3) O n Figure 19.1'-binaphthyl-3. 4’.2'-dihydroxy-1.1’-bi-2=naphthol. Pu’s rigid denderimers constructed around an optically pure diacetate of 4. slight decrease of ee was observed upon going from the first generation to the third generation dendrimer (entries 10-12).[95] For comparison. the size of the dendritic wedges of 65 did not significantly influence the enantioselectivity of the catalyst (entries 2-5). The chiral dendritic BINOL ligands 64-66 were successfully prepared in moderate yields through several chemical transformation reactions. solvent = toluene. the corresponding zero generation 3 2 4 compounds 65-G and 66-G were also synthesized. El-Shehawy dicarboxylic acid and Fréchet-type polyether dendrons with primary and secondary amine at the focal point.0: 0. respectively (see Figure 19).284 Ashraf A. Asymmetric addition of diethylzinc to benzaldehyde catalyzed by (R)-Binol ligands in the presence of Ti[OCH(CH3)2]4a. b Determined by chiral GLC analyses. As shown in Table 8. The recovered ligands showed the same enantioselectivity and reactivity (entry 6).2:3 (molar ratio). c Recycle chiral dendritic BINOL ligand was used. another two aldehydes were used as substrates. when using benzaldehyde as substrate. In order to further demonstrate the size/generation effect of the dendritic BINOL ligand 65. which was converted to 1-phenyl-1-propanol in more than 98% yield and with no byproduct. When using orthochlorinated benzaldehyde as substrate.[95] Asymmetric induction of the above-mentioned dendritic BINOL ligands in the enantioselective addition of ZnEt to aldehydes in the presence or in the absence of 2 Ti[OCH(CH ) ] was investigated. Upon completion of the reaction. All these dendritic chiral BINOL ligands 0 0 were found to be highly effective and chemoselective in the titanium-catalyzed addition of diethylzinc to benzaldehyde. . reaction temperature = oC. The absolute confiruration of product is R. similar enantioselectivities were obtained as compared with those of benzaldehyde (entries 7-9).[95] Table 8. In the case of meta-chlorinated benzaldehyde. a Benzaldehayde: ligand: ZnEt2 =1. reaction time =7hr. chiral BINOL ligands were quantitatively precipitated by the addition of methanol and recovered via filtration. reaction time = 7hr. (R)-65 gave high conversion. toluene. The (dendritic BINOL) Ti(IV) complexes were proved to be efficient catalysts for the enantioselective addition of diethylzinc to various kinds of aromatic aldehydes (Table 10).[96] Figure 20. On the other hand. (R)-66 offered the highest enantioselectivity in the asymmetric addition of diethylzinc to benzaldehyde in the absence of Ti[OCH(CH ) ] (Table 9. a Benzaldehyde : ligand : ZnET2 =1. In contrast to (R)-64 and (R)-65. The same authors also examined the use of these dendritic BINOL ligands in catalyzing the enantioselective reaction of benzaldehyde with diethylzinc in the absence of Ti[OCH(CH ) ] (Table 9). b Determined by chiral GLC analyses. and the molar ratio of BINOL in dendritic ligands to Ti(O-iPr)4 was 1:10 as the reaction conditions. entries 3 and 4).Unique Design Tools for the Synthesis and Design of Dendrimers … 285 Table 9. Dichloromethane was chosen as the reaction solvent.[95] 1 Recently. The absolute configuration of product is R.0: 02: 3 (molar ratio). the enantioselectivity decreased upon going from 66-G to 660 G (entries 3 and 4). reaction temperature = 0 oC. . new Fréchet-type dendritic BINOL ligands bearing several BINOL units at the periphery [(R)-67 and (R)-68] have been successfully synthesized (Figure 20). Asymmetric addition of diethylzinc to benzaldehyce catalyzed by (R)-BINOL and dendritic BINOL ligands in the absence of Ti[OCH(CH3)2]4a. albeit much lower enantioselectivity as compared to 64 (entries 1 and 2).[95] It was found that these chiral dendritic ligands performed 3 2 4 very differently from the BINOL and 64. solvent. This was possibly 3 2 4 due to the formation of better catalyst through the coordination of nitrogen on the linker to zinc atom. high yields and good enantioselectivities were achieved for benzaldehyde (entries 1-2). 1naphthaldehyde (entries 3-4). As shown in Table 10.1% ee. the enantioselectivity decreased with the increase of generation (entries 7-8).[97] . After five times recycles. When (R)-67-G0 and (R)-68-G1 were used.3% ee and 87. The recovered ligand was reused to the asymmetric addition of diethylzinc to benzaldehyde. using the catalysts derived from these dendritic BINOL ligands. El-Shehawy Table 10. the BINOL-functionalized MPC was easily recovered. respectively. the addition of diethylzinc to benzaldehyde gave high enantioselectivity to afford the corresponding alcohols with 87. After completion of the reaction.[96] The recyclability of the dendritic ligand (R)-68-G1 (Figure 20) in the reaction system was examined. disulfides bearing (R)-1. m-methoxybenzaldehyde (entries 5-6).1’-bi-2-naphthol ((R)-BINOL) moieties at each terminal position have been successfully introduced on the surface of Au cluster (Scheme 18).[96] In an interesting approach.286 Ashraf A. The dendritic ligand (R)-68-G1 was quantitatively precipitated by the addition of methanol and recovered via filtration. TiBINOLate complex generated from the obtained monolayer-protected Au cluster (MPC) promoted catalytic asymmetric alkylation of benzaldehyde with Et2Zn affording the addition product in up to 98% yield with 86% ee. and p-halobenzaldehyde (entries 9-14). The high catalyst activity of MPC supported BINOL catalysts would reflect the naked character of BINOL moieties on the surface of MPC. the yield and enantioselectivity were hardly reduced. As for p-methoxybenzaldehyde. Asymmetric addition of diethylzinc to different aldehydes catalyzed by dendritic BINOL ligands. moderate enantioselectivities (entries 15-16) with such ligands were obtained. As far as o-bromobenzaldehyde was concerned. [98] N OH N N OH OH N N OH N N OH 69-(G1) HO R1 CHO + R2 2Zn 71a-c R2=i-Pr. The dendritic chiral ligands 76 and 77 bearing four and eight sites of chiral amino alcohols.[98] In the presence of chiral dendrimer 69-(G1) (3. respectively (Table 11. have been reported on the synthesis of chiral dendrimers with three or six chiral β-amino alcohol moieties on hyperbranched hydrocarbon chain-ends (Scheme 19). The enantioselective addition of dialkylzinc to aldehydes was examined using dendrimers 69 (G1) and 70 (G2) as chiral catalysts (Scheme 18). benzaldehyde (71a) was isopropylated with i-Pr2Zn to give (R)-2-methyl-1-phenylpropan-1-ol (72a) in high enantioselectivity (86% ee) (Table 11.3 mol%) toluene R1 R R2 OH 72a-c (R2=i-Pr) 73a-b (R2=Et) N HO HO N 70-(G2) Scheme 19. The catalysts 69-(G1) and 70-(G2) themselves are soluble in toluene. Chiral diamine 74 and diimine 75 possessing ephedrine moieties were also prepared. entries 2 and 3).3 mol%). Et Chiral catalyst 69 or 70 (3. entries 7 and 8). Thus. the rigid backbones of 69-(G1) and 70-(G2) are effective at impairing an unfavorable intramolecular interaction between the catalytic sites. respectively. Furthermore. entry 1). and were recovered and reused without any loss of enantioselectivity (Table 11. were prepared by attaching ephedrine derivatives at the periphery of polyamidoamine (PAMAM) (Figure 21). Soai et al have been further reported on the synthesis of other structures of chiral dendrimers bearing also chiral β-amino alcohols on their hyperbranched chain-ends. The results are summarized in Table 11. enantioselective isopropylation of benzaldehyde and 2-naphthaldehyde catalyzed by higher-generation dendrimer 70-(G2) yielded 72a and 72b in 80 and 86% ee. Soai et al.Unique Design Tools for the Synthesis and Design of Dendrimers … 287 Scheme 18. These chiral ligands serve as highly enantioselective . 288 Ashraf A.ee was determined by HPCL analysis using chiral column. Aldehyde (71) R1 phenyl (R). d 4. Enantioselective alkylation of various aldehydes using chiral catalyst 69 (G1) and 70 (G2). respectively (Figure 22). El-Shehawy catalysts and ligands in the enantioselective addition of dialkylzincs to aldehydes with up to 93% ee. Configuration of 72a and 72c are tentatively assigned based on that of 72a. c Recovered catalyst was used.3 mol% of chiral catalyst and the mixture was stirrect at room temperature for 15-96h. b .Alcoholb R 2 Entry 1 2 3 4 5d 6 7 8 a a Chiral catalyst 69-(G1) 69-(G1) 69-(G1)c 69-(G1) 69-(G1) 69-(G1) 70-(G2) 70-(G2) 72a 73a 73a 72b 73b 72c 72a 72b Yield (%) 63 61 64 59 50 67 70 32 ee (%) 86 78 77 84 86 77 80 86 71a i-pr Et Et i-pr Et i-pr i-pr i-pr 2-naphthyl p-tolyl phenyl 2-naphthyl 71b 71c 71a 71b Reaction was perfomed in tulene.[99] Chiral dimer 78 was also prepared. HO N H N N H N 74 OH HO N N OH HO N OH N N N N OH HN NH O NH HN HN NH HN HO N NH 75 O O N HN HN O N N N O NH NH N O O HO N N OH O HN N OH NH N O O O O HN NH N HO NH N H HN HN O N O N HN O NH NH HN HN NH NH HN O N HO N N OH HO N OH 76 77 Figure 21. 2.2 molar equiv. The .[99] Table 11. of dialkylzinc was added to a solution of aldehyde and 3.1 molar equiv of diethylzinc was used. The same authors also synthesized chiral dendrimers 79 and 80 bearing four and 12 chiral ephedrine sites. chloroform and dichloromethane. These chiral catalysts were employed in the enantioselective addition of dialkylzincs to aldehydes. These polymers were obtained in high yields. Hu et al have been synthesized optically active ephedrine-bearing dendronized polymers 81 and 82 by using the Suzuki coupling polymerization (Figure 23). Chiral dendritic catalyst 80 could be recovered and used without any loss of reactivity and enantioselectivity. respectively. They are soluble in common organic solvents such as THF. Mn = 50 400 (PDI = 2. diethylzinc adds to benzaldehyde to afford the addition product (R)-1-phenyl-1-propanol in 75% ee and 73% ee. When chiral dendritic catalyst 80 (1. toluene.[99] The ee reached 93% in the addition of diisopropylzinc to 3-phenylpropanal. enantiomerically enriched sec-alcohols with 8393% ee’s were obtained.[100] The application of ephedrine-bearing dendronized polymers 81 and 82 as macromolecular chiral catalysts for the asymmetric addition of diethylzinc to benzaldehyde was investigated and compared the catalytic properties with their corresponding linear polymeric and dendritic chiral catalysts. using catalyst 80 was attained in the enantioselective addition of diisopropylzinc to 3-phenylpropanal.[99] OH N Si Si N HO OH N OH Si N N OH OH N Si OH N N OH 78 N Si Si Si Si Si OH N Si OH OH N Si Si Si Si Si N Si Si HO Si Si Si Si Si N HO N N HO Si Si HO N HO N N HO HO 79 80 Figure 22. 93% ee.[100] The dendronized polymers 81 and 82 were found to be more efficient than their corresponding linear polymeric. Gel permeation chromatography (GPC) analysis (polystyrene standards) shows the molecular weight of 81 is Mw = 141 100. It should be noted that the enantioselectivities attained by using chiral dendritic catalysts 79 and 80 are comparable with those attained by using chiral dimer catalyst 78 (Figure 22). The highest. and the backbone hardly coordinates to dialkylzinc reagents.Unique Design Tools for the Synthesis and Design of Dendrimers … 289 carbosilane backbone is more flexible than the poly(phenylethyne) backbone.80).7 mol%) bearing 12 chiral sites was employed. In the presence of 5 mol% of 81 or 82 (based on the polymer repeat unit) in toluene. Dendronized polymers 81 and 82 could be easily recovered by filtration and . 76% ee). Silica supported dendritic chiral B-amino alcohols. El-Shehawy reused. Regardless of the catalyst used. In addition. 2S)-ephedrine. Benzyl alcohol is formed via the reduction of benzaldehyde by diethylzinc in the absence of catalyst and this reaction proceeds slowly in a competitive way.290 Ashraf A. the reaction performance could be improved to the level of the homogeneous counterpart by increasing . In all the cases with dendritic series. selectivity.[101.[100] HO N Ph Ph OH N HO N Ph Ph OH N n n OR OR n n OR OR OR n n OR OR n n OR C C C C 81. the reaction yielded 1-phenyl-1-propanol as the major product with chemical yields up to 92% and enantioselectivities up to 62% ee.102] O N N H N O O N N H N O N OH * * 2 2 2 2 O O Si O Silica H N Figure 24. The dendritic chiral catalysts that are shown in Figure 24 were prepared via the reactions of various dendrimers with (1R. and enantioselectivity decreased with an increase in the number of generations. N HO Ph Ph N OH N HO Ph Ph N OH Rhee et al have been reported on the first use of silica supported dendritic chiral auxiliaries for the enantioselective addition of diethylzinc to benzaldehyde. n = 0 82. The recovered 81 shows the same reactivity and enantioselectivity (99% conversion of benzaldehyde after 12 h. The reaction performance is strongly dependent upon both the number of generations and the amino group content of initiator sites. n = 1 R = n-C6H13 Figure 23. the conversion. 8 and 16 chiral ephedrine moieties PS(Ephed). The influence of the molar ratios of the dendritic chiral catalyst was also examined (Table 12). 2S)-PS(Ephed)4 N OH Me Ph OH Me N Ph N Me OH (1R.. The enantioselective diethylzinc addition reaction to benzaldehyde using the macromolecular chiral catalysts PS(Ephed)2-PS(Ephed)16 was first investigated. entry 7) was found to be comparable to that reported for the same reaction using the corresponding monomeric chiral catalyst (1R. Furthermore. Interestingly. 2S)-PS(Ephed)8a (1S. 2S)-PS(Ephed)2 OH Ph * N Me OH Me Me Ph * * N Me * * Ph HO Me N Me Me Ph N Me Me Me N Me Ph OH Me N Me OH Ph (1R. 2S)-PS(Ephed)16 Figure 25.2S)-N-benzylephedrine (92% ee.Unique Design Tools for the Synthesis and Design of Dendrimers … 291 the diethylzinc concentration. the polymer backbone hardly to coordinate with the dialkylzinc reagent and each chiral site of the dendritic chiral catalyst is anticipated to work independent of other chiral sites. These chiral dendrimers were evaluated as chiral ligands for the enantioselective diethylzinc addition to a series of aldehydes. 2R)-PS(Ephed)8b Ephed = Ephedrine Me Ph OH Ph OH (1R. entry 7) under otherwise identical reaction conditions.[101. Table 12. Structures of chain-3nd functionalized polystyrenes having 2. The results are summarized in Table 12. entry 7). According to his design.e. It is more interesting to note that the high enantioselectivity observed in the asymmetric diethylzinc addition to benzaldehyde using chiral dendrimer PS(Ephed)8a (90% ee. The chemical yield as well as the enantioselectivity of the addition product was increased markedly on using PS(Ephed)8a that having eight ephedrine moieties (90% and 94% ee. the diethylzinc addition reaction to benzaldehyde using the recovered dendronized polymer PS(Ephed)8a afforded the addition product with a comparable result to that of entry 7 (entry 12).[103] Ph Ph Ph Me N OH Me OH Me N Me * * Ph Ph OH N Me Me Ph * * OH Me N Ph OH N Me OH N Me Me Me Ph Me Me Me OH HO Ph N Me N Me OH Me N Me N Ph OH Me Ph OH N Me Me N Me Ph OH Ph Me OH N Me OH N Me * * Me Me Ph Me Me N * * Ph OH Me n Me Ph N Me OH n Me OH Ph Me * n Me N N Me * * n OH Ph Me Me OH N Me N Me OH Ph Me Ph N Me Me (1R. .102] El-Shehawy et al have recently described an interesting approach for the synthesis of a new kind of dendronized polymers with chiral ephedrine incorporation at the polystyrene hyperbranched chain-ends PS(Ephed)2-PS(Ephed)16 that are shown in Figure 25 with hydrocarbon backbone chains (i. without any heteroatoms either in the polystyrene main chain or in the dendritic chain-ends). the dendritic chiral catalyst could also be recycled and reused without a significant loss of catalytic activity. 4. respectively. Catalytic enantioselective diethylzinc addition to benzaldehyde using chiral dendrimers PS(Esped)2-PS(Ephed)16a.1).2M equiv of diethylzinc and 6 mol% of chiral dendrimer. c The ee values were determined by HPCL analysis using a chiral stationarly phase. a All Reactions were performed in toluene at 0oC using 2. a All Reactions were performed in toluene at 0oC using 2. 2S)-N-benzylephedrine. Yields after purification by column Chromatography (hexane/ethyl acetate =4. b Table 13.292 Ashraf A. El-Shehawy Table 12. . e Data in parentheses are obtained from the same reaction using (1R. Catalytic enantioselective addition of dialkylzinc reagents to aldehydes using dendritic chiral PS(Ephed)8a a. c Determined by HPCL analysis on a chiral stationary phase (Chiralcel OD-H). d Absolut configurations were determined by comparing the sign of their specific rotations with those reported in the literature. d The absolute configureations were assigned by comparing the sign of their specific rotations with those reported in the literature.2M equiv of diethylzinc. b Isiolated yields after flash Chromatography. The results are shown in Table 14. 77. bearing eight chiral sites of ephedrine moieties. the enantioselectivity remarkably increases with more reactive substrates (compare entries 11 vs 7 and 9 and 12 vs 8 and 10. 76. was further demonstrated in the dialkylzinc addition reaction to a series of substituted aldehydes and the results are summarized in Table 13. These above-mentioned chiral dendrimers were used as chiral ligands for the enantioselective addition of diethylzinc to N-diphenylphosphinylimines. have been reported on the first example for the use of dendrimeric chiral ligands in the enantioselective alkylation of imines. Table 13). 2-methyl-5-phenyl-3-pentanol with a high enantioselectivity of 95% ee (entry 13).[103] 6. and 84 were prepared by loading a chiral ephedrine moieties on starburst PAMAM dendrimers (see Figures 21 and 26).Unique Design Tools for the Synthesis and Design of Dendrimers … 293 The catalytic efficiency of the dendronized chiral catalyst PS(Ephed)8. N-diphenylphosphinylamine 86a with >90% ee was obtained.[105] . Chiral diamines 74. and 77 as well as diimines 75.[103] Interestingly.[104-109] Soai et al. There was very little difference in the enantioselectivities between the imino type and the corresponding amino type chiral ligands (75 and 74 & 83 and 76).[105] HO N N OH OH N HO N N OH N HN N NH O N HN HN O N O N O NH N NH HN N O NH O HO N O O N N N H HN N O N O N N O NH NH N N N O O NH N O N O O HN N N HO N N OH OH HN N NH N HO 83 N HO N OH 84 Figure 26. The obtained results revealed that the dendritic chiral catalyst PS(Ephed)8a promotes the highly enantioselective addition of dialkylzinc reagents to all aromatic substituted aldehydes. Dendrimeric chiral ligands 76. In the presence of chiral diimine 75 and diamine 74. Most importantly.3. 83. respectively. the N-alkylimine type chiral ligand 75 was not alkylated during the ethylation reaction of N-diphenylphosphinylimine 85a.2. and 84 afforded 86a with moderate enantioselectivities. the diisopropylzinc addition to 3-phenylpropanal proceeded in a highly enantioselective manner to give the corresponding secondary alcohol. 83. Because dialkylzinc hardly adds to Nalkylimine even in the presence of amino alcohols. Dialkylzinc Addition to Imines Soai’s and his co-workers have been made high efforts on the modification of PAMAM dendrimers with ephedrine ligands giving dendritic catalysts for the rarely reported addition of dialkylzinc to imines. t. Ph H Ph N P Ph Et O (R)-86a (R)-86a + Et2Zn Chiral Ligand (mol%) 75 74 83 76 84 77 50 50 50 50 50 25 Time (d) 2 2 2 2 2 3 Yyield (%) ee ( %) 54 46 32 18 12 8 92 92 43 40 39 30 Molar ratio immine: ET2ZN = 1:6. The enantioselective ethylation of various N-diphenylphosphinylimines (85a-d) in the presence of 50 mol% of chiral ligands 75. r. 74 and 83 (Table 15) was also investigated. El-Shehawy Table 14. Enantioselective addition of diethylzinc to N-diphenyl-phosphinylimine 85a using varios dentic chiral ligands.t. r. Enantioselective addition of diethylzinc to N-Diphenylphosphinylimines 85a-d. Table 15.294 Ashraf A. Imines . H Ph Ph * N Ph P Et O 86a-d Product 86 Yield (%) 86a 86b 86c 86d 86a 86b 86c 86d 86a 86b 86c 86d 54 27 52 54 46 11 41 38 32 10 25 22 ee (%) 92 74 90 93 92 71 89 93 43 11 47 56 Entry 1 2 3 4 5 6 7 8 9 10 11 12 Chiral Ligand 85a 85b 85c 85d 85a 85b 85c 85d 85a 85b 85c 85d 75 75 75 75 74 74 74 74 83 83 83 83 Time (d) 2 2 2 2 2 2 3 2 2 3 3 4 Molar ratio immine: Et2Zn = 1:6. Ph N Ph + Et2Zn P O 85a-d Imine 85 R phenyl 1-naphthyl 2-naphthyl p-tolyl phenyl 1-naphthyl 2-naphthyl p-tolyl phenyl 1-naphthyl 2-naphthyl p-tolyl Ph chiral ligand 50 mol%) toluene. Ph N Ph Ph P O 85a Entry 1 2 3 4 5 6 chiral ligand toluene. 109] Chiral dendrimer 69 (0. respectively (see. (see Figure 22) have been also synthesized and evaluated as chiral ligands in enantioselective diethylzinc addition to N-diphenylphosphinylimines.[108. four and 12 chiral ephedrine sites. Chiral dendrimers 78-80 bearing two. Thus. The results are shown in Table 17.17 mol. equiv. a b All Reactions run in toluene at room temperature using 3.0 molar equiv of diethylzinc.) of a higher order generation also accelerates the reaction to give enantiomerically enriched (R)-N-diphenylphosphinylamines 11 with 85-90% ee in yields of 74-79% (entries 5-7).[105] In order to attain high enantioselectivity by using a chiral dendritic catalyst and ligand. without heteroatoms. the same authors devised chiral dendrimers 69 and 70 with hydrocarbon [poly(phenylethyne)]. Table 16. Scheme 19). The enantioselective addition of diethylzinc to N-diphenylphosphinylimines using dendritic chiral ligands 69 and 70 was examined and the results are shown in Table 16.d were ethylated to afford the corresponding addition products 86a. and the backbone hardly coordinates to dialkylzinc reagents. Determined by HPCL analysis using a chiral stationary phase. i. Chiral dendrimer 70 (0.[106. The enantioselectivities of the addition products with the para-tolyl substituent using 75 and 76 reached to 93% ee (entries 4 and 8).d with very high enantioselectivities in the presence of either chiral dendrimers 75 or 74.Unique Design Tools for the Synthesis and Design of Dendrimers … 295 85a.[107.109] The carbosilane backbone is more flexible than the poly(phenylethyne) backbone. Enantioselective addition of diethylzinc to various Ndiphenylphosphinylimines using chiral dentritic legands 69 and 70. respectively.e.. with a backbone bearing three and six chiral ephedrine derivatives at the periphery. it was necessary to avoid unfavorable coordination between the dialkylzinc reagent and the framework of the dendrimer.109] Each chiral site of the dendritic catalysts and ligands 69 and 70 is expected to work independently of other chiral sites because of the relatively rigid phenylethyne and approximately planar structure of the backbone.34 mol equiv) promotes the highly enantioselective addition of diethylzinc to N-diphenylphosphinylimines 10 to produce enantiomerically enriched (R)-N-diphenylphosphinylamines 11 with 71-94% ee in 73-80% yields (entries 1-4).c. .c. 25 mol equiv). the enantioselective addition of diethylzinc to Ndiphenylphosphinylimine derived from 2-naphthaldehyde. Similarly. a Reactions was run in toluene at 0oC for 48 h using 3 molar equiv of diethylzinc. Highly enantioselective addition of dialkylzincs to Ndiphenylphosphinylimines using chiral dendritic ligands 79. The obtained results are summarized in Table 18. promoted by chiral carbosilane dendrimer 79 (0.13 mol equiv) afforded the corresponding (R)-Ndiphenylphosphinylimine with 92% ee in 70% yield (entry 7). equiv. c Recovered chiral dendrimer was used. The enantioselectivities of chiral dendritic ligands 79 and 80 are comparable with those of chiral dimer 78.296 Ashraf A. have recently described the synthesis and application of a new kind of dendronized polymers with chiral ephedrine incorporation at the polystyrene hyperbranched chain-ends PS(Ephed)n as highly effective chiral ligands for the enantioselective diethylzinc addition to a series of N-diphenylphosphinoyl arylimines (see Figure 25).) of dendritic chiral ligand 80 also produced the imine with 90% ee in 70% yield (entry 8). the addition of diethylzinc to the same imine using the chiral dendritic ligand of a higher generation 80 (0.80 or chiral dimer 78.[110] The enantioselective diethylzinc addition reaction to N-diphenylphosphinoyl benzaldimine 85a as a standard substrate using chiral dendrimers PS(Ephed)2-PS(Ephed)16.083 mol. in toluene at room temperature for 48 h. El-Shehawy Table 17. The use of a lesser amount (0. b As shown in Table 17. Chiral ligand 79 was recovered and reused without any loss of reactivity and enantioselectivity (entries 1 and 2). was first examined. Diisopropylzinc could also be used (entries 4 and 11). Determined by HPCL analysys using a chiral stationary phase.[110] . afforded the corresponding (R)-N-diphenylphosphinylimine with 92% ee (entry 1). El-Shehawy et al. entry 5) was higher than that observed in case of using PS(Ephed)16 (Table 18. the enantioselectivity observed in the diethylzinc addition reaction to imine 85a using chiral dendrimer PS(Ephed)8a (90% ee. Chiral polymer PS(Ephed)8b .2S)-N-benzylephedrine (92% ee. f Values in parenthesis are obtained by using N-vinylbenzylephedrine copolymerized with strene and divinylbenzene as Chiral ligand. This was probably due to the fact that the environments of active sites at the polystyrene chain ends of PS(Ephed)8a might have enough space to work as a chiral ligand. on performing the diethylzinc addition reaction to benzaldimine 85a using each of PS(Ephed)2 and PS(Ephed)4. It is worth to mention that all the dendritic chiral polymers used in this study are soluble in toluene and worked well as homogeneous chiral ligands during the reaction.0 molar equiv of (1R. Interestingly. entry 5) was high as those obtained not only by using (1R. Table 18.5 molar equiv of chiral polymer. 2S)-Nbenzylephedrine as chiral ligand. b Refers to the isolated yields wafter flash chromatography (hexane/ethylacetae). the addition product 86a was obtained in higher yields with slightly higher enantioselectivities. Interestingly. but for longer reaction times (Table 18. entry 5) as chiral ligand. while the active chiral sites of PS(Ephed)16 interfere either with each others and/or with the polymer backbone chains. Under the same reaction conditions.0 molar equiv of diethylzinc and equimolar amounts of chiral polymer (based on the total number of ephedrine moieties against the imine) and imine 85a except for entry 7. Enantioselective diethylzinc addition to N-diphenylphospinoyl imine 85a using chiral dendrimers PS(Ephed)na. entry 6) as chiral ligand. entry 5) but also by using polystyrene supported with the same chiral moiety (89% ee. respectively). which was perfomed using 1. entries 2 and 4. d The absolute configuration was assigned to be R by comparing the retention time on HPCL with those reported in literatur3e.Unique Design Tools for the Synthesis and Design of Dendrimers … 297 Table 18. the enantioselectivity of the addition product 86a obtained by using PS(Ephed)8a (Table 18. e Values in parenthesis are obtained from the same reaction using 1. a All reactions were performed in toluene at room temperature using 3. c Deterermined by HPLC analysis on a chiral column (Chiralpak AD). 0 molar equiv of diethylzinc and equimolar amounts of chiral polymer (based on the total number of the ephedrine moieties against immine) and imine 85 except for entry 14. e Recovered dendritic chiral polymer was used. 2S)=PS(Ephed)8aa All reations were performed in the toluene at room temperature for 48h using 3. El-Shehawy worked well as chiral polymer PS(Ephed)8a and led smoothly to the desired secondary chiral amine 85a with almost the same chemical yield and enantioselectivity. entry 8). c Determined by hpcl analysis on a chiral column (Chiralcel OD or Chiralpak AD). d The absolute configuration was assigned by comparing the retention time on the HPCL with those reported in literature. Enantioseletive diethylzinc addition to N-diphenylphosphinoy1 arylimines 85 using chiral dendrimer (1R. b Refers to the isolated yields after flash chromatography (hexane/ethlacetate). Table 19. chiral dendrimer PS(Ephed)8a promotes the highly enantioselective addition of diethylzinc to all aromatic substituted phosphinoyl imines 85 to afford the corresponding enantiomerically enriched (R)-N-diphenylphosphinoylamides 86 with yields of 83-93% and enantioselectivities up to 93% ee (Table 18). in the presence of the dendritic chiral ligand PS(Ephed)8a that showed the best result. a The diethylzinc addition reaction to a series of N-diphenylphosphinoyl arylimines (85).5 molar equiv of chiral polymer.[110] As it was expected.298 Ashraf A. but with reversed stereoselectivity (Table 18. was examined and the results are summarized in Table 19. It is interesting to note that phosphinoyl imines bearing parasubstituents on their phenyl groups would provide the corresponding N-phosphinoylamides . which was performed using 0. the G2 dendritic metalloporphyrins showed 2. the diethylzinc addition reaction to imine 85 (Ar=4-MeC6H4) using the recovered polymer PS(Ephed)8a afforded the corresponding addition product (entry 13) without any significant loss in the enantioselectivity as in entry 4. This regioselectivity provided by the dendritic catalyst is by far not as . Epoxidation of Alkenes Suslick and his co-workers have been designed dendritic chloromanganese(III) porphyrins (Figure 27) for the catalysis of epoxidation of alkenes with iodosylbenzene.to 3-fold higher selectivity toward 1-alkenes relative to the nondendritic catalyst.or metasubstituted phenyl groups.112] The dendritic wedges are first. based on the total number of the chiral sites at the periphery. in the epoxidation of a mixture of 1-alkene and cyclooctene. the obtained high yields and enantioselectivities of the addition products suggested that nearly all of the chiral sites at the periphery of dendritic ligand PS(Ephed)8a worked effectively.[110] Figure 27. The least hindered double bond of unconjugated dienes such as 1. The chiral polymer was easily and quantitatively recovered by silica gel column chromatography followed by reprecipitation from its THF solution to a mixture of methanol and HCl. 6.20-tetraphenylporphyrinatomanganese(III) cation.4-heptadiene and limonene is epoxidized preferably.15. and the catalyst provides much better intramolecular and intermolecular regioselectivities than those obtained with unsubstituted 5. Since the author have used in this study an equimolar amount of the dendritic chiral polymer PS(Ephed)8a. against imines.4.[111.10.and second-generation aromatic polyesters.Unique Design Tools for the Synthesis and Design of Dendrimers … 299 with relatively higher enantioselectivity than their analogues having ortho. As shown in Table 19. They provide a confined environment. Similarly. and they were fully characterized by 1H NMR. 13C NMR. El-Shehawy high.6′triphenylphenylporphyrin).112] The dendrimers 87-96 with and without peripheral vinyl groups were prepared via several synthetic procedures (Figure 28). however. while air was bubbled through the reaction mixture. 88. Thus. followed by stirring at room temperature for a further 12 h in the presence of LiCl.[111. as that of the classical picket-fence porphyrin.114] The authors have been examined the epoxidation reaction on several phenyl substituted and the results are collected in Table 20. The epoxidation reactions were generally run with 20 mol% of Mn-Salen.20-tetrakis(2′.15. two equivalents of m-chloroperbenzoic acid (m-CPBA) as oxidant and five equivalents of 4methylmorpholine-N-oxide (NMO) as additive in CH2Cl2 at -20 oC (Scheme 20). by MALDI-TOF or Hi-ResMALDI spectrometry. Figure 28.[113.4H2O for several hours in EtOH/toluene.[113] In most cases. 91. and IR spectroscopy.10.4′. The manganese complexes of the dendritically substituted Salens were investigated to check whether the dendritic modification gives rise to any change in the catalytic activity in solution. the dendrimers were obtained in yields between 75 and 95% after purification by flash column chromatography.300 Ashraf A. Salens 87. 5. and by elemental analysis. and 92 were loaded with Mn by heating a solution of Salen and Mn(OAc)2. . mediated by Mn complexed of Salens 87. The selectivities and conversions obtained in the epoxidation of styrene ( 97a) with Salens 87 and 91 were comparable to those obtained with the corresponding (and . 91 and 92. Epoxidation of various olefins mediated by Mn-salens 87.2 equiv Mn(Cl)-salen 2 equiv m-CPBA 5 equiv NMO CH2Cl2. 91 and 92 in homogenous solutions. Solective and converstions obtained in the expoxidation of various olifins.Unique Design Tools for the Synthesis and Design of Dendrimers … 301 R1 R4 R2 R3 0. -20 oC O R1 O R2 R4 R3 97a-f O O a O b c O d e O f Scheme 20. Epoxide 97 a a a a b b b c c c d d d d e e e e f f f a Salen 87 88 91 92 87 88 91 87 88 91 87 88 91 92 87 88 91 92 87 88 91 Conversion [%]a) 87 80 79 82 94 83 92 90 58 80 90 75 83 76 94 97 93 98 12 7 8 er 73:27 83:17 72:28 84:16 76:24 84:16 76:24 53:47 55:45 53:47 96:4 92:8 95:5 89:11 89:11 90:10 91:9 89:11 57:43 52:48 59:41 After 30 min. 88. 88. Table 20. determined by capillary gas chromatography (CGC). The corresponding Mn-Salens were prepared according to literature procedures. Mn (C1) in homogenous solution to give epoxied 97a-f. The catalytic activity of the metallosilicates after calcination revealed excellent activity and selectivity towards epoxidation of alkenes.302 Ashraf A. yields calculated for TBHP were high.[117] Scheme 21. the least nucleophilic terminal alkenes such as 1-octene and 1-decene were least reactive and required higher reaction temperatures for reasonable yields. 88. In contrast. From the results as described in Table 21. Neumann et al have been synthesized new metallosilicate catalysts by reacting a silanol capped dendrimer. as a probe substrate. conversion complete after 15 minutes). 2-Methyl-2-heptene was more reactive than 2-octene but there was some loss of selectivity when the former was used as substrate. 91. WVI and VV) (Scheme 21). whereas in the case of trans-stilbene ( 97f) the enantiomer ratios were poor. it is clear that TBHP is more effective than H2O2 and that Mo–SiO2 > Ti–SiO2 > V–SiO2 > W–SiO2. epoxidation of dihydronaphthalene ( 97e) gave rise to high enantioselectivities. In general. the selectivities obtained in homogeneous solution using Salens 87. Since Mo–SiO2 and Ti–SiO2 were both active and quite stable to reaction conditions when using anhydrous TBHP as oxidant. and 92 are similar to those reported for the classical Jacobsen catalyst under comparable conditions. conversion complete after 1 h). again similar to the results obtained with unsubstituted Jacobsen catalyst under the same conditions (er 91:9. The resulting Si[CH2CH2Si(CH3)2OMCp2Cl]4 compounds were incorporated in a silica matrix by the sol-gel method. Thus. and 92 in the epoxidation of 1-phenyl cyclohexene ( 97d). Si[CH2CH2Si(CH3)2OH]4 with MCp2Cl2 (M = TiIV. Additionally. reactivity was clearly a function of the nucleophilicity of the alkene.[113.116] Also. 91. .[117] As may be expected.115. a highly reactive alkene. A preliminary assay to determine catalytic activity for epoxidation of alkenes with hydrogen peroxide and tert-butylhydroperoxide (TBHP) was carried out using cyclooctene. again comparable with the results obtained with the simple unsubstituted Jacobsen catalyst. El-Shehawy commercially available) Jacobsen catalyst under identical conditions (er 75:25. 88. enantiomerically highly enriched products and high degrees of conversions were observed with dendritically modified Salens 87. MoVI. these materials were further tested for activity in epoxidation of a series of alkenes by TBHP (Table 22). 8h. 1ml 2M TBHP in n-decane. a Conversion (selectivity) (mol%) Substrate Cyclooctene Cyclohexene 1-octene b Ti-SiO2 95 (99) 44 (92) 25 (81) 17 (76) 21 (97) 29 (90) Mo-SiO2 >99(99) 71 (93) 56 (95) 61 (95) 62 (98) 90 (90) 1-deceneb 2-octene 2-methyl-2-heptene a Reaction conditions: 1 mmol substrate. 60oC.a Substrate cis-2-hexen-1-ol trans-2-hexen-1-ol cis-3-hexen-1-ol trans-3-hexen-1-ol 5-hexen-1-ol a Conversion (selectivity) (mol%) 74 (96) 87 (97) 60 (>99) 85 (>99) 6 (>99) Reaction conditions: 1 mmol substrate. .a Metallosilicate None Ti-SiO2 V-SiO2 Mo-SiO2 W-SiO2 a 303 Conversion (selectivity) (mol%) Oxidant 30% H2O2 0 39 (98) 12 (94) 46 (99) 51 (85) Oxidant 6 M TBHP 2 95 (99) 81 (95) >99 (99) 20 (99) Reaction conditions: 1 mmol cyclooctene. 8h. Expoxidation of alkenes catalyzed by Ti-SiO2 and Mo-SiO2 with terbutylhydroperoxide. 60oC. Table 22. 2 mmol 30% H2O2 + 1 ml methanol of 1 ml 2 M TBHP on n-decane. 8h b 100oC Table 23. Expoxidation of cyclooctene catalysed by metallosilicates.Unique Design Tools for the Synthesis and Design of Dendrimers … Table 21. Epoxidation of alkenols catalyzed by Mo-SiO2 with ter-butylhydroperoxide. 12 mg metallosilicate catalyst (2 mol% M on SiOd). 60oC. 12 mg metallosilicate catalyst (2 mol% M on SiOd). 1 ml 2M TBHP in n-decane. 12mg metallosilicate catalyst (2 mol% Mo on SiOd). third-. whereas 5-hexen-1ol reacted like a terminal alkene. Remarkably. The chiral dendrimers were synthesized as shown in Scheme 23. El-Shehawy The molybdenum containing silicate Mo–SiO2 was also surveyed for activity in the epoxidation of alkenols with anhydrous TBHP (Table 23).[119-121] Table 24. These salen-imitating ligands were complexed with Mn(II) and used as catalysts in olefin epoxidation (Scheme 22 and Table 24). the yield of the epoxidation of styrene increased more than twofold in this series. in the epoxidation of styrene. the yield increased from 20% for generation 0 to 75% for the fourth-generation catalyst.[119-121] O N H N N H NH2 NH2 (i) O OH N N H O H N N O Mn N O O (ii) Mn(CH3COO)2 O R Ph Catalyst R = H or Ph Ph O R PAMAM-dervatized silica or regular silica Scheme 22. and fourth-generation catalysts.[117] Rather unusually the allylic alcohols were only slightly more reactive than the homoallylic alcohols. Epoxidation of styrene with supported dendritic.304 Ashraf A. Even though the Mn loading per gram of silica was almost equal for the second-. Selectivity was high. Catalyst generation 0 1 2 3 4 Yield (%) 20 26 36 53 75 Zhao et al have been established an operationally simple and mild protocol for the catalytic enantioselective epoxidation of enones using a series of chiral pyrrolidinylmethanolbased dendritic catalysts and tert-butyl hydroperoxide (TBHP) as an oxidant. in the case of allylic alcohols 3-4% of the allylic aldehyde was formed as by-product. The Kawi group[118] prepared a similar PAMAM on silica template while amino terminal groups were converted into salicylimines. a reaction of growing importance in synthetic organic chemistry.[122] . the catalytic activity per Mn equivalent increased dramatically with the dendron generation. Preparation of PAMAM-based supported dendritic Mn catalyst for the epoxidation reaction. Thus. Unique Design Tools for the Synthesis and Design of Dendrimers … 305 Scheme 23. Table 25. Screening reaction conditios for the epoxidation of 111a a). O Cat./ TBHP solvent, rt O O 110a 111a Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 a Catalyst 105 105 104 106 107 108 109 106 107 + 4 Å MS 109 + 4 Å MS 109 + 4 Å MS 108 + 4 Å MS 108 + 4 Å MS 108 + 4 Å MS 108 + 4 Å MS Solvent Hexane CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4 CCl4/hexane = 1:1 Benzene CH2Cl2 CCl4 Oxidant TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP TBHP H2O2 T (oC) rt rt rt rt rt rt rt rt rt rt 0 rt rt rt rt T (h) 48 144 120 144 144 144 144 144 144 144 144 96 96 144 48 Yield (%)b Trace 60 59 64 73 67 70 85 86 84 80 65 66 20 0 ee(%)c nde 66 41 67 68 69 71 69 73 74 13 66 69 54 --- (config)d ------------------------------- Unless otherwise specified, the reaction was carried out with 1.2 equiv of TBHP in the presence of 30mol% of catalyst. b .After column chromatography. c Enantiomeric excess was determined by the HPCL analysis using chiral Daicel Chiralce OD column. d .The absolute configuration was determined to be (2R, 3S) bu comparison of the HPCL Cretention time with know data. e .Not determined. 306 Ashraf A. El-Shehawy A preliminary study was performed to test the catalytic property of these reagents in the asymmetric organocatalytic epoxidation of enones 13a with TBHP (Table 25). In general, good conversion of enone 110a was achieved, and the corresponding optically active epoxide 111a was obtained in good yields. The enantioselectivities were moderate to good (41-71%), with the (2R,3S)-configured product 111a was formed predominantly (Table 25, entries 2-7). Among all the dendritic chiral catalysts evaluated in this reaction, the second-generation ligand 109 was the best one in terms of yield and ee (Table 25, entry 7).[122] To demonstrate the scope and potential for the organocatalytic epoxidation, a series of different substituted enones 110 were reacted with TBHP at room temperature in the presence of dendritic chiral ligand 109 (30 mol %) as the catalyst. The results are summarized in Table 26. As shown, almost all reactions proceeded in reasonable reaction times when 30 mol % of 109 was used at room temperature and diastereoisomerically pure trans-(2R,3S)-epoxides 111 were obtained. Different types of electronic substitution on the phenyl ring of the carbonyl group furnished results comparable to those achieved in the epoxidation of 110 (Table 26, entries 2-5). It was found that enones with para electron-withdrawing substituents in the βphenyl group were all converted to the corresponding optically active epoxides in good yields and enantioselectivities (Table 26, entries 6 and 7). However, under the same reaction conditions, an electron-donating substituent did not react with TBHP, due to its low reactivity (Table 26, entry 8).[122] Tabke 26. Catalytic enantioselective epoxidation of enones promoted by dentritic lignad 109 and TBHPa. a Unless otherwise specified the reaction was carried out with 1.2 equiv of TBHP in the presence of 30 mol% catalyst 109. b After colomn chromatography. c Enantiomeric excess was determined by the HPLC analysis by using the chiral column. d The Absolute configureation was determined to be (2R.3S) by comparison of the HPCL retention times with known data. e Using xx-diphenyl-L-prrrolidinemethanol as the bifuncion organocatalyst. f 50 mol % catalyst was used in this reaction. g Not determined Unique Design Tools for the Synthesis and Design of Dendrimers … 307 The recyclability of these catalysts was examined. After the completion of the reaction, dry methanol was added to the reaction mixture, and the dendritic catalyst 109 was almost quantitatively precipitated and recovered via filtration. The recovered dendritic catalyst 109 was reused at least five times with little or no loss of activity and enantioselectivity (Table 27).[122] Table 27. Recylcing use of dendritc catalyst 109 in asymmetric exposidation of chalcone 110 a. Entry 1 2 3 4 5 a Catalyst 109 109 (second) 109 (third) 109 (fourth) 109 (fifth) T (h) 144 144 144 144 144 Yield (%)b 84 84 80 81 83 ee (%)c 74 73 72 73 72 Unless otherwise specified the reaction was carried out with 1.2 equiv of TBHP in the presence of 30 mol% of catalyst. b After column chromatography. c Enantiomeric excess was determined by the HPLC analysis using a chiral Daicel Chiralcel OD column. 6.5. Palladium-Catalyzed Asymmetric Reactions Palladium catalysts are one of the most frequently used catalysts in organic synthesis. There is a large body of literature on palladodendrimer-catalyzed reactions during the last decade whereby the molecular palladium complex is covalently or supramolecularly attached to the dendrimer (including silica- or polymer-supported dendrons).[1m,123,124] This whole area has been recently reviewed in excellent and comprehensive reports by the groups of Newkome[125] and de Jesús[126] with catalyzed reactions including alkene hydrogenation, hydrovinylation, polymerization, and copolymerization, carbon-carbon coupling (Stille, Suzuki-Miyaura, Sonogashira), allylic substitution, aldol-type condensation with isocyanoacetates, and Michael addition. As with other catalysts, the most important problems are the cost related to the catalyst efficiency including turnover number of the catalyst (TON), turnover frequency (TOF), and removal of the catalyst from the reaction mixtures for both economic (catalyst recycling) and ecological reasons (prevent pollution of the reaction product by the catalyst).[127-129] Chemoselectivity, regioselectivity, stereoselectivity, enantioselectivity, and diastereoselectivity, optimized with homogeneous catalysts, are the other key issues.[130] van Leeuwen is one of the pioneers of the field of dendrimer catalysis. When he was at Shell, his group reported a star-shaped hexaphosphine-palladium catalyst with a benzene core for polyketone formation from alternating CO/alkene polymerization. While the monometallic catalyst gave 50% fouling (precipitation of the polymer on the wall of the reactor), this star-shaped catalyst gave only 3% fouling, possibly for solubility reasons. This 308 Ashraf A. El-Shehawy is also a very early dendritic effect.[69,131,132] The van Leeuwen group synthesized a series of diphosphine ligands centered on 1,1′-bis-diphenylphosphinoferrocene bearing dendritic carbosilane substituents at the para aryl positions in a divergent manner (Figure 29).[132b] Figure 29. van Leeuwsen’s diphospine lignads centered on 1.1’-bis-diphenylphosphinoferrocene bearing dendritic carbosilane subsituents at the para aryl positions whose palladium complexes catalyze allyic alkylations. Reactions with [Pd(MeCN)2Cl2] afforded the ferrocene-centered chelate complexes, and these metallodendrimers were shown to be efficient in palladium-catalyzed allylic alkylation (Scheme 24). The linear trans-product was mainly obtained. The rate of the reaction decreased, however, as the dendritic generation increased. This negative dendritic effect was attributed to the more difficult mass transport with increasing the steric bulk of the dendritic wedges and was more pronounced when going from generation 2 to 3. Remarkably, the size of the metallodendrimer also determined the selectivity of the allylic alkylation reaction, because the dendritic bulk hindered the attack of the nucleophile on the Pd-allyl moiety. Steric interactions between the branches and increase of the P-Pd-P bite angle preferentially lead to the linear product.[132b] Unique Design Tools for the Synthesis and Design of Dendrimers … cata. Cl ( Pd Ph 309 Ph + O EtO O O OEt 2 + L EtO O O OEt Ph + EtO O O OEt L= dendritic diphosphine Scheme 24. Scheme 25. Synthesis of chiral dendrimers 114-G3. van Leeuwen’s group has also synthesized functionalized carbosilane dendrimers. Their palladium complexes have been used as catalysts in the allylic alkylation performed in a continuous membrane reactor.[132c] The second-generation carbosilane dendrimer served as a starting point. It is a white solid whose X-ray crystal structure could be determined and whose molecular volume of 2414 Å3 was anticipated to be large enough for separation of the catalyst from the reaction mixture by nanofiltration. The phosphine-functionalized dendrimers of generation 0, 1, and 2 were synthesized by hydrosilylation of double bonds with chlorodimethylsilane or dichloromethylsilane followed by reaction with Ph2PCH2Li/TMEDA. The dendritic phosphine of higher generation such as that with 72 phosphines could not be prepared because of steric congestion. The phosphine dendrimers were allowed to react with [PdCl-(η3-C3H7)]2 yielding either bidendate palladium phosphine dendrimers or mixtures when monodentate dendritic phosphines were used as ligands. All the metallodendrimers were used as catalysts in the allylic alkylation of allyl trifluoroacetate and sodium diethyl methylmalonate yielding diethyl allylmethylmalonate. The reaction was first carried out in a batch process, and all the metallodendrimers showed a very high catalytic 310 Ashraf A. El-Shehawy activity. Using 0.2% of catalyst, the yield was larger than 80% after 30 min and only small differences of reaction rates were observed for the different catalysts. In a continuous process using a membrane reactor, the metallodendrimer containing 12 chelated palladium atoms with a calculated volume of about 7600 Å3 was used as the catalyst. The retention of this catalyst in the membrane reactor was determined to be 98.1%, which corresponds to a calculated value of only 25% of decreased activity after flushing the reactor 15 times. Samples taken from the flow were not catalytically active, which confirms that the observed decrease of activity was due to decomposition of the palladium complex and not to loss of the dendritic catalyst.[132c] Majoral et al. have been reported on the synthesis of a third generation phosphoruscontaining dendrimer possessing 24 chiral iminophosphine end groups derived from (2S)-2amino-1-(diphenylphosphinyl)-3-methylbutane. The reaction proceeded gently overnight at room temperature to yield the chiral dendrimer 3-G3 isolated in 88% yield after work up as a white powder, very sensitive to oxidation (Scheme 25).[133] In situ complexation of this dendrimer by [Pd(η3-C3H5)Cl]2 affords a catalyst, which is used in asymmetric allylic alkylations of rac-(E)-diphenyl-2-propenyl acetate and pivalate. The percentage of conversion, the yield of isolated 2-(1,3-diphenylallyl)-malonic acid dimethyl ester, and its enantiomeric excess have been measured in each case, and were found to be good to very good (ee from 90% to 95%). Furthermore, the dendritic catalyst could be recovered and reused at least two times, with almost the same efficiency.[133] Majoral et al reported on the synthesis of chiral ferrocenyl phosphine-thioether ligands covalently bound on the periphery of 4 phosphorus dendrimers (generations 1-4) having a cyclotriphosphazene core and on one model compound.[134] The chiral dendrimer were obtained in nearly quantitative yield after work up. These dendrimers proved to be efficient ligands for the palladium-catalyzed asymmetric allylic substitution reaction of dimethylmalonate under classical conditions. The reaction times for completion were almost the same for the dendrimers of different sizes and the corresponding monomeric ligand.[134] In every case, isolated yields of the allylated products were very high and enantioselectivities very close to the one observed for the corresponding monomeric analogue (ee up to 93%). The reuse of the dendritic catalysts has been carried out simply by precipitation with pentane at the end of the catalytic reaction. Indeed, these organometallic dendrimers were found to be efficient soluble polymer-supported catalysts. Heck olefin arylation, one of the most widely used reactions in synthetic organic chemistry, was successfully accomplished in solution with aryl iodides, bromides, and even chlorides, using a variety of catalytic systems.[1d,124,135-137] Heterogeneous catalysis, however, was performed almost entirely with iodides or electron-deficient bromides,[138,139] mainly using metal palladium adsorbed on an inorganic support.[140] The uses of the Heck reaction encompass a vast spectrum of applications, from the synthesis of fine chemicals, drugs, and natural products to the preparation of novel materials and supramolecular devices, and include intermolecular and intramolecular versions as well as asymmetric variants.[1m,124] The biphosphine-terminated PAMAM-on-silica system prepared from ethylenediamine (see Scheme 16) was complexed to a dimethylpalladium fragment with (TMEDA)PdMe2 as a precursor. Before this study, similar soluble systems were prepared and studied by Reetz and coworkers.[137] As for Rh complexation, the poor functionalization of the third- and fourthgeneration-derived supported catalysts prevented their conclusive investigation. The zero- Unique Design Tools for the Synthesis and Design of Dendrimers … 311 generation to second-generation supported catalysts demonstrated activity comparable to that of the homogeneous analogue in the Heck reaction of bromobenzene (Scheme 26). X R + Y P Me Pd Me NaOAc, DMF, 48 h, 120 oC P R Y PAMAM-derivatized silica or regular silica Scheme 26. Heck reaction catalyzed by PAMAM-based support catalysts. Figure 30. Bidente third-generation DAD phosphinated Pd dendrimer for Sonogashira and Suzuki copling reactions. Jayaraman compared three generations of Pd-alkylphosphine dendrimers in the Heck reactions with various olefins and reported that the second and third generations were found to exhibit better catalytic activity than the monomer and first-generation metallodendrimers.[141] This trend was also noted by Mapolie with poly(propyleneime)iminopropylpalladium [142]. On the other hand, three generations of bidentate DAB phosphinated Pd dendrimers that were found to be active in Sonogashira coupling of iodo- and bromobenzene with phenylacetylene showed a negative dendritic effect attributed to increasing steric effect as the generation increases (example for iodobenzene at 25 ◦C, time for quantitative conversion: model: 30 min; first-generation: 15 h; secondgeneration: 40 h; third-generation: 48 h) (Figure 30). These metallodendrimers can be recovered and recycled with little decrease of efficiency up to seven cycles with bis- 312 Ashraf A. El-Shehawy cyclohexylaminoalkylephosphine ligands (conversion is 39% after 7 cycles for the thirdgeneration catalyst). The nature of the alkyl substituents (cyclohexyl versus tert-butyl) on the P ligand of the Pd catalyst also plays a role in efficiency, solubility and thus recycling ability.[143-145] A number of other Pd-catalyzed processes were examined with supported dendritic systems. The Suzuki reaction was found to be less sensitive to the nature of the dendritic backbone. The groups of Alper, Arya, and Manzer used the phosphinated PAMAM–silica constructs to immobilize a variety of Pd complexes. The formed structures were extensively studied and tested as heterogeneous catalysts in the iodoarene carbonylation reaction (Scheme 27).[146] Quantitative complexation was observed with zero-generation-to-secondgeneration-derived ligands for the PdCl2 fragment. However, for higher generations and with bulkier Pd fragments, only partial functionalization was achieved. The catalytic reaction was optimized, and quantitative conversions were readily obtained. With respect to the influence of the dendritic template structure on the reaction outcome, two trends were observed. First, higher generation-derived catalysts were characterized by lower Pd loadings and lower conversions per silica weight unit. However, when the reactivities per Pd equivalent (or TON/TOF as presented in this article) were compared, they were found to increase with the generation (Table 28). Second, the leaching of Pd from the support decreased upon an increase in the dendrimer generation. It is possible that some of the displayed activity resulted from Pd(0) nanoclusters immobilized inside the silica/dendritic matrix because blackening of the silica was usually observed under these reaction conditions and no reactivity with bromobenzene was observed (Pd metal catalysts are usually only reactive toward iodides, whereas palladium–phosphine complexes are expected to catalyze reactions of both iodobenzene and bromobenzene). Regardless of the true nature of the catalyst in the methoxycarbonylation reaction, the demonstrated dendritic effects were quite remarkable. I R P X Pd P X R O C OMe PAMAM-derivatized silica or regular silica (R= H; 4-NO2; 4-Me; 2-MeO; 4-MeO, 4-CF3; 4-I; 4-Br; 4-OH; 4-CH3CO; 4-I-C6H4) Scheme 27. Carbonylation reaction catalyzed by PAMAM-based support catalysts the reagents and conditions are as follows: NET3, MeOH and CO. Table 28. Methoxycarbonylation of Iodobenzene with Support Dentritic Catalysts. Unique Design Tools for the Synthesis and Design of Dendrimers … 313 The Alper group[147] reported also on a Pd catalyzed transformation, hydroesterification of olefins (Scheme 28), based on C6-spacer-containing PAMAM dendritic catalysts supported on silica. Because of the longer diamine used in the PAMAM dendron construction, the phosphine–palladium catalyst could be prepared on up to fourth-generation dendrons. All the catalysts demonstrated high activity, a preference for the linear product, and moderate recyclability. R1 P + R2OH + CO X Pd P X R1 CO2R2 + R1 CO2R2 PAMAM-derivatized silica or regular silica (Reagents and conditions: nonpolar solvent, 150 psi, and 115 oC) Scheme 28. Hydroesterification reaction catalyzed by PAMAM-based support catalysts. Moreover, silica-supported polyamidoamine (PAMAM) dendrimers with different spacer lengths were prepared.[148] After the introduction of diphenylphosphino groups, complexation to dibenzylidenepalladium(0) gave the desired silica-supported dendrimerpalladium catalyst complexes G0 to G4-C2-Pd (Figure 31). These catalysts showed activity towards the oxidation of terminal alkenes to methyl ketones. A dependence of catalytic activity on the spacer length of the diamine in PAMAM was observed. The authors have examined the catalytic activity of these dendrimer-Pd complexes towards the oxidation of terminal alkenes to methyl ketones using tert-butyl hydroperoxide as oxidant.[148] Figure 31. Dendritic catalysts. Initially the authors have attempted to oxidize terminal alkenes to methyl ketones under Wacker-type conditions using the catalysts G0 to G4-C2-Pd. Attempts to optimize the Wacker-type conditions using Pd complexes of silica-supported PAMAM dendrimers, as catalysts were unfruitful. Consequently, the oxidant was changed to tert-butyl hydroperoxide. As a benchmark, the catalytic performance of G0 was investigated using different alkenes. The addition of organic solvents inhibited the oxidation reaction, and thus the reactions were carried out under neat conditions. Cyclohexene gave the lowest yield not surprising because 314 Ashraf A. El-Shehawy internal alkenes are usually less reactive than terminal alkenes (Table 29, entry 1). 1-Octene gave higher product yields than 1-decene and 1-tetradecene (Table 29, entries 2-4).[148] Table 29. Oxidation of various alkenes using TBHP as oxidant. Catalyst Go-Pd (dba), the Pd content in the reaction mixture was 0.5 mol% substrate (1.50 mmol). TBHP (1.65 mmol). 55o , C. 24h. [a] Yield by GC. The catalytic activity also proved to be a function of the dendrimer backbone. The higher generations were less active when screened using 1-octene. Only the first-generation dendrimer complex gave the methyl ketone in reasonable yield (Table 30, entry 2). The second and third-generation dendrimer complexes gave poor yields (Table 30, entries 3 and 4). This poor activity was attributed to steric congestion of the dendrimer. This leads to the threshold for dendrimer growth being reached. Extending the chain length of the diamine used during dendrimer synthesis can bring relief to steric crowding.[148] Table 30. The effect of dendrimer generation. Catalyst Gn-Pd(dba). The Pd content in the reaction mixture was 0.5 mol%. 1-octene (1.50 mmol). TBHP (1.65 mmol). [a] Yield by GC. The various silica-supported PAMAM-Pd catalysts displayed comparable activity towards the oxidation of 1-hexene. Extending the olefin length by two methylene groups starting from 1-hexene to 1-tetradecene gave different results. The different catalysts started to show different activities. The monomeric catalyst and 1st generation C6 and C12 catalysts once again gave comparable results. G2-C6 gave the highest conversion of 1-octene while G2C12 gave the lowest. A similar trend was observed for 1-decene. In the oxidation of 1tetradecene, the G0 and G2-C6 catalysts gave good yields while G2-C12 gave lower yields.[148] These catalysts could be recycled. The G0 catalyst can be reused up to eight times giving good yields of 2-octanone. Meanwhile, G1 and G2 complexes can be reused four It has been recognized that the nature of the macromolecular support plays a significant role in solid-phase organic synthesis. This catalytic system could be applied to other substituted alkenes. Compatibility problems between reagent or substrate and the polymer support can greatly limit the applications of a given support. considerable research remains to be done. and the variety of dendrimer generations provides a unique means to improve catalyst supports. Some studies in these fields have definitely shown that dendrimers have beneficial or even superior characteristics. although it should be noted that frequently more simple monomeric or polymeric systems are equally effective with respect to the investigated application. The perfect definition of catalytic sites and the clear possibility to recover the dendritic catalysts have been fully demonstrated. soluble polymer-supported reagents and catalysts have been utilized.Unique Design Tools for the Synthesis and Design of Dendrimers … 315 times. By establishing homogeneous reaction conditions while still facilitating product separation. 4-Methyl-1-pentene could be oxidized in comparable yield to 1-hexene. Steric congestion may sometimes result in positive dendritic effects in terms of selectivity. but steric constraints limit the access to the . 1. For terminal olefins with internal bonds like 5-vinyl-2norbornene. Over the past three decades. in the case of substrates that possess limited solubility. Catalytic efficiency is very often marred by steric congestion at the metallodendritic surface. covalent attachment to a soluble support would allow their use in a previously inaccessible range of synthetic applications. dendrimers have evolved from a concept to become a new class of polymers with a unique architecture and versatile chemical structures. the longer chain diene. the multiple sites provide an exceptional density of catalysts. soluble polymer-supported methodologies have demonstrated utility in a variety of areas including peptide synthesis. polymer-supported reagents. The precision of the dendrimer structures. Seminal studies by van Leeuwen and Brunner’s dendrizyme concept opened the field of dendrimer catalysis.8-nonadiene. Interestingly. and polymer-supported catalysts. To overcome these limitations. the specificity of their topology. With peripheral catalyst loading. There is much more than the aesthetic attraction in the use of dendrimers in the field of catalysis.5-hexadiene gave a dimerization product in addition to single double bond oxidation. research on dendrimers is not only focused on disclosing aberrant or special features of dendrimers but considerable effort is also invested in the development of applications for dendrimers. and then Reetz introduced recycling. Although great strides have been made in the use of soluble polymers as supports for recoverable reagents and catalysts. The refinement of current liquid-phase methodologies coupled with the development of new soluble polymeric supports tailored for organic synthesis combine to make soluble polymers an increasingly valuable tool for synthetic chemists. only the terminal double bond was oxidized. was only oxidized at one double bond while 1. CONCLUDING REMARKS The use of soluble polymers provides an alternative platform for organic synthesis by incorporating beneficial aspects of both solution-phase and solid-phase chemistry. Progress in controlled polymerization and synthesis techniques have led to the development of wellcontrolled dendrimers structures with a large number of surface groups that can be utilized to display a wide range of applications. Furthermore. Good yields were obtained for the oxidation of 4-phenyl-1-butene. 7. small-molecule organic synthesis. Today. Since there is no single solution to the catalyst separation problem it is not expected that dendrimers will provide the general solution.316 Ashraf A. H.. 39. 1857. (a) El-Shehawy A.-A. 3325. 3819. (b) Itsuno S. however. Rev.. Rev. 2003. Polym. Abdelaal M.. J. El-Shehawy catalytic centers as shown by several of our examples. (i) Dahan A. (f) Dickerson T. H. E. 8. 3717.. 1731. Chem. J. 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E-mail: chmmlw@sunrise. pesticides. it has become an important choice in organic synthesis and is widely applied in the manufacturing processes of specialty chemicals. Taichung County. such as drugs. 43302 Taiwan. Successful completion of reactions involving lipophilic and hydrophilic reactants can be achieved by employing an environmentally benign technology viz. ingenious new analytical and process experimental techniques viz. monomers etc. As a result. Safety and Health. additives for lubricants.Vivekanand and Maw-Ling Wang* Hungkuang University. improved reaction rates. perfumes. Tel: +886-4-2631-8652 ext. Chapter 10 RECENT STRATEGIES IN PHASE TRANSFER CATALYSIS AND ITS APPLICATION IN ORGANIC REACTIONS P. Fax: +886-42652-9226. Republic of China. Inc. due to these salient features. ABSTRACT In view of the increasing environmental and economical concerns.tw.4175.hk. . lower reaction temperatures and the absence of expensive anhydrous or aprotic solvents. Some of the prominent features of the PTC include. Shalu. ultrasound and microwave irradiation assisted PTC transformations have become immensely popular in promoting various organic reactions. it is now imperative for chemists to invent as many environmentally benign catalytic reactions as possible. Currently.A.edu. pharmaceuticals. PTC is considered to have great potential for industrial-scale application. Republic of China. dyes.. Hungkuang University. Owing to its simplicity and the low cost of most of the phase transfer catalysts. researchers incessantly invented new and novel phase transfer catalysts with more active-sites and higher efficiency. Nowadays. Cinchona alkaloids and ephedrine derived catalysts are the most popular chiral PTC that has been employed to achieve the goal for inducing asymmetry into product molecules. Taiwan.In: Homogeneous Catalysts Editors: Andrew C. ‘‘phase transfer catalysis’’ (PTC).. Poehler ISBN: 978-1-61122-894-6 ©2011 Nova Science Publishers. Due to ever increasing necessity of increasing the efficiency of PTC in industries. Phase transfer catalysis will be of curiosity to * Corresponding author: Department of Environmental Engineering. 326 P. However. ultrasonic and microwave conditions are described. The necessity of selective transformations in agrochemical and pharmaceutical industries is even larger since delicate bioactive compounds are often not robust enough to stand the conditions used in bulk chemistry. the greening of global chemical processes has become a foremost topic in the universe. and other energy inputs. etc. these techniques are industrially unattractive. we have proposed to present recent happenings in the field of PTC and to study its applications to various organic reactions. plant protection agents. Nevertheless these methods have their own shortcomings viz. . are used. catalysts. For successful completion of a reaction it is necessary that the reactants collide with each other as much as possible. Further. Typical applications of PTC in silent.. constrained and polluting. successful completion of reactions involving lipophilic and hydrophilic reactants can be achieved by employing an environmentally benign technology viz. it is now imperative for chemists to invent as many environmentally benign catalytic reactions as possible. are less desirable. Generally. in view of the increasing environmental and economical concerns. to deliver sustainable chemical design. dyes. Catalysts aided selective transformations eliminate the requirement of stoichiometric auxiliary reagents and can eventually help to decrease the amounts of waste. usually require a number of chemical operations in which additional reagents. However by proficient design of chemical transformations we can reduce the required energy input in terms of mechanical. photographic chemicals. life scientists. As a consequence.. ‘‘phase transfer catalysis’’ (PTC). kinetics of various organic reactions catalyzed by PTC carried out under a wide range of experimental conditions will be presented. solvents. high stirring speed. chemical transformations. INTRODUCTION In recent years.. by the design of environmentally compatible chemical reactions. Transformations of starting materials into desired final products of practical applications such as pharmaceuticals.Vivekanand and Maw-Ling Wang anyone working in academia and industry that needs an up-to-date critical analysis and summary of catalysis research and applications. synthetic and biological chemists. offers the tools to approach pollution and sustainability concerns at the source. monomers etc. Green chemistry [2]. However it is often noticed that these reactions are immiscible in nature. thermal. and the associated environmental impacts of excessive energy usage. In general. environmentalist toxicologists. Classical methods [3] to overcome this immiscibility include use of protic/aprotic solvents. To alleviate the predicament of immiscibility it is necessary to ferry water soluble anionic reactant into organic soluble reactant/organic phase. high temperature etc. In addition. The development of new synthetic methods that are more environmentally benign have been propelled by the growing importance of green chemistry in organic synthesis [1]. green chemistry is the only way forwards: it merges expertise from physical. high energy consumption. together with that of. they are able to carry out the necessary synthetic transformation in a more environmentally benign way.A. Thus. production of byproducts and difficulty in purification together with environmental pollution. which produce in addition to the desired product large amounts of byproducts and waste. In view of the success and vitality of this technique. alkylation [19]. often the most expensive reagent in the process. and monomers for polymer synthesis. Emergence of the Methodology Owing to its simplicity and the low cost of most of the phase transfer catalysts. Aldol condensations [20]. chiral reactions etc. e. oxidation. Escalating demand for homochiral commercial products in preference to their racemic counterparts has resulted in the rapid growth of numerous asymmetric transformations. pesticides. hexadecyl tributyl phosphonium bromide. As a result. Some of the prominent features of the PTC include. dyes. Starks et al. researchers placed much effort on the development of phase transfer catalysts which could induce asymmetry into product molecules [14]. researchers incessantly invented new and novel phase transfer catalysts with more active-sites [7-13] and higher efficiency. etherification. Popularity of catalytic asymmetric reactions is due to the usage of only less than a stoichiometric amount of the chiral control element. whereas organic reactants and catalysts are located in the second. Michael additions [15]. Nowadays.. Also. PTC is considered to have great potential for industrial-scale application. Frequently employed PTC are presented in Table 1 and is a very effective tool in many types of reactions. lower reaction temperatures and the absence of expensive anhydrous or aprotic solvents. It makes use of heterogeneous two-phase systems-one phase (water) being a reservoir of reacting anions or base for generation of organic anions.[5] reported that nucleophilic aliphatic substitution reaction of an aqueous sodium solution with 1chlorooctane does not ordinarily take place because of immiscibility. The reacting anions are continuously introduced into the organic phase in the form of lipophilic ion-pairs with lipophilic cations supplied by the catalyst. Chiral centers in catalysts derived from the . Darzens reactions [16]. asymmetric Baylis-Hillman [22] reaction has been developed using derivatives of quinidine to effect the reaction of activated alkenes with aldehydes. With the development of PTC. carbene addition. Diels-Alder cycloadditions [18]. organic phase. Asymmetric PTC has been used in several types of reactions including. perfumes. hydrolysis. PTC becomes an important choice in organic synthesis [6] and is widely applied in the manufacturing processes of specialty chemicals.g. utilizes water as the solvent and is applicable to a great variety of reactions in which inorganic and organic anions and also carbenes react with organic substrates. and α-hydroxylation of ketones [21]. leading to waste minimization. such as pharmaceuticals. reduction. the PTC technology has found universal adoption. Asymmetric phase-transfer catalysis has attracted considerable attention as a convenient technique for the synthesis of chiral molecules. By the addition of 1% of the quaternary ammonium. esterification. cyanide ions are ferried into the organic phase from the water phase and 1-cyanooctane formed quantitatively in a matter of minutes. alkylation. improved reaction rates. addition. Due to ever increasing necessity of increasing the efficiency of PTC in industries. additives for lubricants. Cinchona alkaloids and ephedrine derived catalysts are the most popular chiral PTC that has been employed to achieve the goal for inducing asymmetry into product molecules. epoxidations [17].Recent Strategies in Phase Transfer Catalysis and its Application … 327 GENESIS OF PHASE TRANSFER CATALYSIS This key green approach [4]. Recovery is difficult and their toxicity poses environmental pollution. Phase Transfer Catalysis Insoluble PTC Soluble PTC IPTC RPTC LLPTC SLPTC LLPTC SLPTC GLPTC Figure 1. such as TADDOL [26]. Merrifield resin-bound cinchonidine and cinchonine have been employed as recoverable PTC catalysts [24. Extensively used. despite high costs and toxicity. and salen-metal complexes [31] have also been used in asymmetric PTC alkylations. Classification of PTC Reactions. Cryptands Highly reactive. Furthermore. Lower in activity and can be recovered easily.328 P.Vivekanand and Maw-Ling Wang cinchona alkaloids are located both on the quaternary nitrogen and on the carbon framework [23]. except in the Stable. binaphthyl derived amines [29. Used sometimes Costlier presence of strong acids. In addition. Table 1. salts Expensive than quaternary ammonium salts. 25]. . spiro ammonium [27] and phosphonium salts [28]. but less stable under basic conditions. Frequently Employed PT Agents PTC Cost Activity and Recovery of Catalyst Stability and Utility Agent Crown ethers Highly active catalysts even under Stable and frequently Very Costlier basic conditions and at higher employed. And widely used.30]. Inexpensive Inexpensive Quternary Fairly active and recovery is Phosphonium relatively difficult.A. due to higher reactivity. Fairly stable under basic conditions and up to 100 oC. More stable than quaternary ammonium salts hence often used. Quternary Ammonium salts PEG Recovery is relatively complicated and moderately active. non-Cinchona chiral catalysts. temperatures. Thermally more stable than quaternary ammonium salts. typical in reactions promoted by alkali. depending on the actual phases involved. a) RX M+XQ+YQ+YRY M+YQ+YQ+XOrganic Phase Interface Aqueous Phase M+Xb) RX M+XQ+YQ+Y- M+YQ+Y- RY M+Y- Organic Phase Aqueous Phase Q+X- Scheme 1. 32]. two main mechanisms have been recognized in phase-transfer reactions: (a) the interfacial mechanism. since the chemically controlled extraction mechanism is independent of the stirring speed above a certain value whereas the interfacial mechanism is strongly dependent on stirring speed. Two types of PTC mechanism a) Interfacial mechanism b) Extraction Mechanism. Other non-typical variants of PTC include inverse PTC (IPTC) and reverse PTC (RPTC) via a reverse transfer mechanism. gas-liquid PTC (GLPTC). which is slowly extracted into the organic phase to swiftly react with an electrophilic substrate (Scheme 1a) and (b) the extraction mechanism where anions are rapidly transferred as ion-pairs from aqueous or solid phase into the organic phase where they slowly react with a substrate (Scheme 1b). and solid-liquid PTC (SLPTC). Further. Mechanism of Phase Transfer Catalysis Mechanism of PTC is broadly classified into two types based on kinetic criteria. and this variant of PTC can be grouped along with traditional insoluble PTC. Within each class. oxanion or azanion). reactions are further classified as liquid-liquid PTC (LLPTC). In some cases. To differentiate between the two mechanisms. 9-13. The distinction between these two mechanisms is always made based on influence of stirring speed and value of energy of activation [7. Accordingly. where interfacial deprotonation converts an anion (such as a carbanion. where the PT catalyst is immobilized on a solid support.Recent Strategies in Phase Transfer Catalysis and its Application … 329 Classification of PTC PTC reactions can be broadly classified into two main classes: soluble PTC and insoluble PTC (Figure 1). the PT catalyst forms a separate liquid phase. to distinguish between the diffusion-controlled mechanism and other PTC/OH- . kinetic run at significantly higher agitation speed is required. In uncatalyzed sonicated reactions. several non-conventional methods are emerging that involve reactions in aqueous media [33] or those that are accelerated by exposure to microwave [34-36] or ultrasound [37–39] irradiation. When a liquid is irradiated by ultrasound. high micromixing will increase the heat and mass transfer and even the diffusion of species inside the pores of the solid [49]. Although. 41-42]. Moreover. grow and oscillate extremely quickly and even collapse violently if the acoustic pressure is high enough. ingenious new analytical and process experimental techniques viz.330 P. the effects of ultrasound are produced due to the phenomenon called cavitation. two types of chemical reaction: (i) the acceleration of conventional reactions by ultrasound and (ii) redox processes in aqueous solutions. In a liquid medium. then the mechanism operative is interfacial mechanism and extraction mechanism is operative if it is below 10 kcal mol-1. the chemical effects of ultrasound. These days this environmental benign technology is combined with PTC with primary objective of optimizing reaction conditions [59-61]. These methods are now recognized as viable environmentally benign alternatives [34–39]. Richards and Loomis [47] reported. Ultrasound irradiation is a transmission of a sound wave through a medium and is regarded as a form of energy for the excitation of reactants consequently enhancing the rate of diffusion [44-46]. In this regard. sonication methods have been initially applied to homogeneous reactions in a variety of solvents. the kinetic order and the energy of activation of the reaction become valid.. this approach has now evolved into a useful technique in heterogeneous reactions. The occurrence of these collapses near a solid surface will generate microjets and shock waves [48]. a large number of organic reactions can be carried out in higher yields. If the energy of activation is above 10 kcal mol-1. INGENIOUS TECHNIQUES IN CONJUNCTION WITH PHASE TRANSFER CATALYSIS Phase transfer catalysis will be of curiosity to anyone working in academia and industry that needs an up-to-date critical analysis and summary of catalysis research and applications. on the chemical effects of high-power ultrasound. microbubbles can appear. efficient and eco-friendly methods for applications in complex organic synthetic manipulations constitutes a major chemical research effort. A vast majority of sonochemical applications in the synthesis deal with reactions involving metals [38. shorter reaction time and milder reaction conditions under ultrasonic irradiation [43]. they also increase the reaction rate and avoid the use of high reaction temperatures [58]. or their aqueous solutions [38. attributed to intense local conditions generated due to cavitation bubble . in the liquid phase surrounding the particles. Inventing selective. 40] organic phase insoluble reagents. ultrasound and microwave irradiation assisted PTC transformations have become immensely popular in promoting various organic reactions. Sonoication has been found to enhance this reaction of liquid–liquid phase-transfer catalysts (LLPTC) bi-phase system. Compared with the traditional methods. Application of ultrasonic waves in organic synthesis (homogeneous and heterogeneous reactions) has been boosted in recent years [50-55].A. Currently.Vivekanand and Maw-Ling Wang mechanisms. Sonication of multiphase systems accelerates the reaction by ensuring a better contact between the different phases [56-57]. Further. the nucleation. Michael reaction. cavitational collapse near the liquid– liquid interface disrupts the interface and impels jets of one liquid into the other.e. with frequencies between 300 MHz (0. there has been significant number of papers have appeared [68–74]. Microwaves are electromagnetic with wavelengths ranging from as long as one meter to as short as one millimeter. nanoparticle synthesis [83] etc. i. the phase-transfer catalyst initiates the reaction by the transfer of species across the interface and ultrasound merely facilitates this transfer. and leading to a dramatic increase in the interfacial contact area across which transfer of species can take place [64]. safe and rapid methodology. It has become recognized that many chemical reactions. esterfication. which has been attributed to its initial lack of controllability and reproducibility coupled with a general lack of understanding of the basics of microwave dielectric heating. SCOPE AND OBJECTIVES In principle. we wanted to present in this chapter the application of recent PTC methodologies to the synthetically important organic reactions. Even after a slow uptake of the technology. Apart from their impact in mainstream organic synthesis. which may be prohibitively long or low yielding using conventional heating. epoxidation. Due to these features. The application of microwave radiation-PTC offers new alternatives in sample preparation in terms of shorter reaction times and reduced solvent consumption. 63]. and coalescence of vapour or gas bubbles in the ultrasonic field [62. Rates of PTC reactions. their influence in the field of medicinal chemistry [78-82]. However in ultrasound in conjunction with PTC reactions systems. microwave irradiation has been increasingly used as a synthetic tool in a number of studies. formation. Researchers have shown much interest in microwave-assisted chemistry to facilitate faster reactions and efforts are now being made to scale up reactions using this technology [75-77]. possibly by increasing the interfacial area across which this transfer occurs [67]. Heck reaction. mainly through an enhancement in mass transfer. 66].Recent Strategies in Phase Transfer Catalysis and its Application … 331 dynamics. It has been reported that a combination of PTC and ultrasound is often better than either of the two techniques alone [65. Alkylation reactions. disappearance. among others. Microwave methodology is a novel approach towards clean and green chemistry and it is relatively a very convenient. Now a days there has been considerable interest in microwave assisted PTC reactions [84-98]. were the . forming fine emulsions. Significant advantage of microwave-enhanced chemistry is the reduction in the reaction times.. has been dramatic. The resultant advantages in comparison to classical heating are especially spectacular. cyanation. aziridine reaction and polymerization reactions. It is clear that microwave chemistry can provide access to synthetic transformations. In such cases. The rate enhancement in PTC assisted reactions is due to mechanical effects. darzen’s reaction. as well as selectivity of the desired product. which require heating are likely to proceed more rapidly using this different form of heating. can be synergistically enhanced by using microwave irradiation. Suzuki coupling.3 GHz) and 300 GHz.. The area is still burgeoning and this is in no small part due to the positive interaction between suppliers of microwave equipment and the research community. or equivalently. however.01 kcal/mol. However.05 g) was added to the reaction . there are only a few papers [104. These days chemist show much interests in imide derivatives because of their numerous applications in biology [100. aziridine reaction. 40 C 2 3 0 Br O N H 1 O N O KBr H2O Scheme 2. The influence of the amount of tetrabutylammonium bromide on the apparent rate constant (kapp) was studied in range 0. many of the contributions to this review are also analyzed from a critical point of view. taking into account the different components and variety of conditions involved in the each of these reactions.0-0. The overall reaction was described by pseudo-first-order kinetics and the apparent activation energy in cyclohexanone was found to be 15. In the control experiments (absence of TBAB). when a small quantity of TBAB (0. Further.105] discussing the synthesis of imide derivatives under solid-liquid PTC (SL-PTC). The main advantage of using solid-liquid process in the reaction is to avoid the slow reaction rate due to hydration in the presence of water. N-alkylation of Succinimide with 1-bromo-3-phenylpropane under S-L-PTC conditions.Vivekanand and Maw-Ling Wang reactions originally to be covered.99% was observed after 2 h of reaction.5-dione (3) was successfully carried out by the reaction of succinimide (1) with 1-bromo-3phenylpropane (2) in a small amount of KOH and organic solvent under solid-liquid phasetransfer catalysis condition [106] almost water free conditions [Scheme 2]. O KOH.332 P. We investigated systematic kinetics of the reaction and predicted the reaction mechanism. ALKYLATION REACTIONS PTC catalyzed alkylation is an important process step in the manufacture of large number of drugs [99]. Heck reaction. PTC Solvent. The chapter is organized according to the subheadings presented in the following section. ultrasonic-PTC assisted synthesis of 1-(3-phenylpropyl)pyrrolidine-2. It is expected that the synthesis of imide under ultrasonic–PTC condition will be more efficient than conventional techniques.101] as well as synthetic [102] and polymer chemistry [103].A. Recently. a conversion of 3. and esterfication whereas the rest of the reactions will be studied in the second part in due course. On the other hand. Because of the abundant literature found on these topics. when possible. we decided to dedicate this first part only to the alkylation reactions.65 g under ultrasonic standard reaction condition. with the aim of discussing the advantages and disadvantages that the different techniques offer and trying to select the best choice. Results indicate that the mass transfer resistance at the solid-liquid interface could be ignored when the agitation speed exceeds 200 rpm. epoxidation. From the plot of –ln(1-x) versus time (Figure 2) it is clear that the apparent rate constant increased linearly with the increase in the amount of TBAB catalyst. 0 × 10-2 mol of succinimide. Thus. In silent condition.97% after 2 h of reaction. Influence of the amount of TBAB catalyst on the apparent rate constants. was increased with the increased amount of TBAB catalyst. Table 2. 6.45 g 0.0 × 10-3 mol of 1-bromo-3-phenylpropane. The concentration of quaternary ammonium cation (Q+) in organic phase solution. 1 g of KOH.15 g 0. 6. 45 °C.05 g 0. (300 W).15 0. 0.1 12. 800 rpm. 0. the reaction rates at 40 kHz and 120 kHz were compared with same output power of 300 W. (kapp) a Amount of TBAB (g) 0 0. Effect of amount of TBAB on the rate of the reaction. but in the presence of ultrasound the conversion is 76% (kapp = 12.1 7.3 g of internal standard (naphthalene). In order to investigate the influence of ultrasonic frequency on the PTC catalyzed alkyalation of succinmide.25 0.3 g of internal standard (naphthalene). which affected the concentration of the active catalyst SUC-Q(org).65 g -Ln (1-X ) 2 1 0 0 20 40 60 80 100 120 Time (min) Figure 2. 40 kHz. 60 mL of cyclohexanone.25 g 0.Recent Strategies in Phase Transfer Catalysis and its Application … 333 solution the conversion increased dramatically to 30.0× 10-2 mol of succinimide. 800 rpm. The results are shown in Figure 3 and Table 3.05 0. 40 kHz (300 W). 60 mL of cyclohexanone. 1 g of KOH.3 ×10-3 min-1) for 40 and .4 23 32 a Reaction conditions: 6. on increasing the amount of catalysts the kapp values increases (Table 2).65 Apparent Rate Constant kapp (x 10-3 min-1) 0. 5 4 3 Amount of TBAB 0g 0. the conversion is only 62% (kapp = 8 × 10-3 min-1).45 0.0 × 10-3 mol of 1-bromo-3-phenylpropane. 6. 45 °C.4 ×10-3 min-1) and 90% (kapp = 19.4 3. Thus. However. Plot of -ln(1 . 60 mL of cyclohexanone. the ultrasonic effect enhances the rate 1. 800 rpm.0 × 10-3 mol of 1-bromo-3-phenylpropane. From these observed results it is clear that the ultrasonic assisted phase-transfer catalysis significantly increased the reaction rate. 0. 6. 6.55 times with respect to the conventional method (agitation speed at 800 rpm only).Vivekanand and Maw-Ling Wang 120 kHz. 6.25 g of TBAB. 45 °C. 1 g of KOH. 0.334 P.4 19. 800 rpm (300 W).5 2.25 g of TBAB.0 0. 1 g of KOH. Table 3.0 0 20 40 60 80 100 120 Time (min) Figure 3.X) of 1-bromo-3-phenylpropane versus time with various ultrasound frequency.0 Ultrasound frequency 0 kHz 40 kHz 120 kHz 1.3 a Reaction conditions: 6. 60 mL of cyclohexanone.Ln (1. We compared the influence of six solvents on the reaction and the order of reactivities of the six solvents is: cyclohexanone > acetophenone > o- .X ) 1. 45 °C.3 g of internal standard (naphthalene).5 . 0.0 × 10-2 mol of succinimide.3 g of internal standard (naphthalene). Further we found that.0 × 10-2 mol of succinimide.A. respectively. 0. the reaction rate is increased by increasing the amount of KOH and amount of SUC-H. Influence of different ultrasound frequencies on the apparent rate constants (kapp) a Ultrsound Frequency (kHz) 0 40 120 Apparent Rate Constant kapp (x 10-3 min-1) 8 12.0 × 10-3 mol of bromo-3-phenylpropane. 2. the reaction rate is decreased by increasing the volume of water and cyclohexanone.5 0. 5-tris((N. By employing dialysis membranes satisfactory results have been obtained in the recovery and reuse of higher generation salts. Among the various PTC’s tested tetraoctylammonium bromide (TOAB) showed significantly higher catalytic activity. [107] and demonstrated that these dendritic cinchonidine ammonium salts (Scheme 3) can be applied as phase transfer catalysts in the alkylation of N(diphenyliminemethylene)glycine (Scheme 4). R2 = Bn d. al. Ph N Ph 5 CO2iPr Cat (10 mol%). The development of more efficient PTC’s is an important goal in organic synthesis so as to increase the catalytic efficiency of these catalysts. derived from cinchonidine and Fréchet dendritic wedges up to generation three.Ntriethylammonioum) methylphenyl)benzene trichloride (TEAMPBTC) and studied its utility . BrN + OR2 N 4 OR1 OR1 a.Recent Strategies in Phase Transfer Catalysis and its Application … 335 dichlorobenzene > chlorobenzene > chloroform > toluene. PhCH2Br. Alkylation of N(diphenyliminemethylene)glycine (5) with benzylbromide catalyzed by a new dendritic cinchonidine-derived ammonium salt (4a). R1 = Bn. R1 = Bn. Vivekanand and Balakrishnan [10] have synthesized and characterized a novel multi-site phase transfer reagent. Chiral dendritic molecules used as phase transfer catalysts in the alkylation of a glycine imine ester. R1 = Bn. R2 = Allyl c. This led to the invention of multi-site phase transfer catalysts.N. Chiral nanosize molecules.3. Recently. R2 = H b. R1 = Me... In this regard. viz. Base Solvent. R2 = H Scheme 3. For first generation catalysts a reversal on the stereoselectivity can be achieved by changing the nature of the inorganic base from KOH to NaOH. The study reveals efficiency of the catalysts are by reaching a moderate level of asymmetric induction. one of the options is to increase the number of catalytic active sites in them. have been synthesized by Guillena et. 1. while the chiroptical properties are independent of the enantioselection achieved. T( C) o Ph N Ph 6 * CO2iPr Ph Scheme 4. less than 5% conversion was detected even after 4 h of reaction.Vivekanand and Maw-Ling Wang in the synthesis of 2-(2-bromoethyl)-5. These PTC reactions were carried out in a liquid–liquid two-phase medium.336 P. The effect of the agitation speed on the reaction rate is shown in Table 4. in the absence of a phase-transfer catalyst and ultrasound. However. Further. PTC mechanism for the thioether synthesis.dimethylcyclohexane-1.3-dione by selective monoalkylation of dimedone under pseudo-first order reaction conditions.5. High yields of products were obtained in shorter reaction time using 4 mol% of the tetrabutylammonium bromide and ultrasound 28 kHz (200 W) conditions. they investigated the catalytic activity of a new quaternary ammonium salt. They found the catalytic activity of the new onium salt is superior compared to other commercial phase transfer catalysts under mild reaction conditions. with three active sites. For agitation speed over 400 rpm. Mechanism of PTC assisted thioether synthesis is presented in Scheme 5. including linear and branched alkyl groups catalyzed by phase-transfer catalysts in combination with ultrasound obviously provides a more efficient synthetic approach for the preparation of thioethers [60]. We investigated a comprehensive kinetic study of thioether synthesis under influence of ultrasound assisted phase-transfer catalysis conditions.+ Na2S (1) Aqueous Phase 2Na+BrScheme 5. The substitution of alkyl bromides (RBr) to sodium sulfide (Na2S). Na2S Rate of the two-phase reaction is influenced by the mass transfer as well as the chemical reaction.A.4-dibromobutane under pseudo-first order condition [11]. 2RBr R2S Organic Phase 2RBr + (Q+)2S + + 2Q+Br-+ R2S (2) Interface 2Na Br + (Q )2S 2Q+Br. the rate of the reaction is insensitive to the agitation speed. in the cycloalkylation of indene with 1. This . 9 39.Recent Strategies in Phase Transfer Catalysis and its Application … 337 can be attributed to the active intermediate of the catalyst (Q2S). 60 min of reaction. 4 mmol of 1-butyl bromide. From this observation. 4 mol% of TBAB. Table 4.8 40.8×10−3 min−1 and in vice-versa the kapp value at 500 rpm is 11. 60 min of reaction.7×10−3 min−1. it is easy to transfer the active intermediate of the catalyst from the aqueous phase to the organic phase. 10 mL water. 4 mol% of TBAB. The reaction follows pseudo-first order law in the presence of PTC and . which is hydrophobic and likes to stay in the organic phase.8 33. the mass transfer rate reaches a constant value when the stirring speed is larger than 400 rpm. Conversions of various reactants with time: 7 g Na2S. presence of ultrasonicwave results in increase in the collision rate between the organic and aqueous phase reactants and decrease the surface area between the two layers [108]. we infer that the ultrasonic effect enhances the rate 3. Influence of different alkylating agents on the rate of thioether synthesis is presented in Fig.6 Figure 4.4×10−3 min−1. Agitation Speed (rpm) 0 200 400 500 600 800 1000 kapp (x 10-3 min-1) 9. In the presence of both condition.7 40. kapp: 7g Na2S.e.6 41.7 40. at 500 rpm combined with the ultrasonic wave frequency 28 kHz (200 W) the kapp value is 41. Thus.e. 10 mL water.. 40 mL n-hexane. i.7 times with respect to the conventional method (stirring speed at 500 rpm only). 35 0C.5 g of biphenyl. 35 0C.. 500 rpm. Further. 500 rpm. 0. 4 and Table 5. 40 mL of n-hexane. in which the interfacial area is not so important. Influence of the agitation speed on the apparent rate constants. i. In the absence of stirring speed and in the presence of the effect of ultrasonic condition at 28 kHz (200 W) the observed rate constant is 9. 6 41.Vivekanand and Maw-Ling Wang excess amount of sodium sulfide. 35 0C.7 25. Further. but in the . Influence of ultrasonic frequenzy on the conversion of 1-butyl bromide: 7 g Na2S. The kinetic investigation reveals that the most reactive organic reactant is allyl bromide and the reaction is 100% completed within 10 min for allyl bromide. 500 rpm.5 5.0. It can be attribute to the the smaller molecular size and the conjugation of pi-bond. 4 mmol of 1butyl bromide.1 11.5 17. kapp (x 10-3 min-1) 49. 4 mmol of 1-butyl bromide. Table 5.Reaction completed within 10 min. At 1 h. 40 mL of n-hexane. Influence of alkylating agents on kapp: 7 g Na2S. 60 min of reactiona (200 W). 4 mol% of TBAB. From 1-propyl bromide (1-C3H7Br) to 1-octyl bromide (1-C8H17Br) the kapp value decreases due to increasing the carbon chain of the molecules and (Q2S) is not able to properly interact with active site of the long chain alkyl bromides. 10 mL water.A. 500 rpm. 10 mL water.338 P.6 - Figure 5.5 g of biphenyl. Among the alkyl bromides sec-propyl bromide (2-C3H7Br) is the least reactive one because of steric hindrance in its reaction. 4 mol% of TBAB. 35 0C.7 9. Alkyl Bromide 1-Propyl bromide 1-Butyl Bromide 1-Pentyl bromide 1-Hexyl bromide 1-Heptyl bromide 1-Octyl bromide 2-Propyl bromide Allyl bromidea a. 40 ml of n-hexane. without ultrasonic irradiation the conversion is only 53%. we compared the reaction rate at 28 kHz and 40 kHz having same output power of 200W. 60 min of reaction. In addition to the expected ethers 8 (a and b). lipoxygenase. So the application of ultrasounds in organic synthesis is one of the popular areas in sonochemistry. Above this concentration there was no further increase in the conversion.ω-dihalides or ditosylates using tetrabutylammonium bromide as phase transfer agent under microwave condition [111b]. Further. In order to minimize the competitive elimination. O-alkylation of mono-benzylated isosorbide and isomannide was performed with various α. 10) with benzyl chloride (11) (Scheme 7) by using tetra-n-butylammonium bromide as a catalyst by Yadav et al. analgesics and for treatment of metabolic disorders.110]. [111a]. halide leaving group was changed to tosylate when competitive SN2±E2 processes is involved (Scheme 6). . The conversion increased only upto a certain concentration of TBAB (6. Authors indicate that microwave-PTC condition enhances the rate of the reaction. 5). These observed results indicate that ultrasonicassisted phase-transfer catalysis significantly increased the yield of the products. mass transfer of ion pair from the liquid film to the bulk liquid was controlling beyond certain concentration of catalyst. The ambient reaction conditions (70% yield) involve the use of only 2% of catalyst in p-xylene for 5 min at 140 0C or in toluene for 15 min at 110 0C. The same trend is also observed by Entezari and coworkers [109. HO O Br-(CH2)8 O O O + OCH2Ph 7a 7b Br-(CH2)8-Br KOH. some amounts of alkene 9 (a and b) were obtained resulting from a dehydrobromination on the common intermediate involved in SN2±E2 competitive processes. platelet. antihypertensive. TBAB O OCH2Ph CH2=CH-(CH2)6 O O O O + OCH2Ph 9a 9b PhCH2O O O (CH2)8 O O 8a 8b O OCH2Ph Scheme 6. diuretics. Alkylation of isosorbide and isomannide performed under microwave assisted phase transfer catalysis condition. [112].7 × 10−5 mol cm-3). Selective mono alkylation of isosorbide and isomannide was carried using tetrabutylammonium bromide and by using potassium hydroxide as a base by Chatti et al.Recent Strategies in Phase Transfer Catalysis and its Application … 339 presence of ultrasonic the conversion is 91% and 97% for 28 kHz and 40 kHz. Authors attribute this to the fact that the reaction rate was fast and thus. prostaglandin and. respectively (Fig. 2-Benzyloxyacetophenone (12) is utilized as a pharmaceutical intermediate for the manufacture of drugs such as antiaggregant. Novelties of low power microwave irradiated solid–liquid phase transfer catalysis have been brought out in the selective O-alkylation of sodium salt of o-hydroxyacetophenone (OHAP. Comprehensive screening of several phase transfer catalysts (Aliquat 336. CsF-Celite. KF-alumina and Aliquat 336 under microwave irradiation in a domestic microwave oven afforded corresponding diaryl ethers (15) in high yields. tetra-n-butylammonium hydrogensulfate (TBAHS).Vivekanand and Maw-Ling Wang Here the rate of mass transfer was less than the rate of reaction. This is the case of homogeneous solubilization. The Gibbs free energy for solid dissolution with anion exchange reaction could be also evaluated. On comparing four PTC’s viz. O-alkylation of substituted phenols under MW-PTC condition. Therefore. Ethers are commercially attractive because of their extensive applications in the fine chemicals industry. and TBAB) together with various inorganic bases (K2CO3. Control experiments (absence of PTC’s) resulted in small yield of ethers. reagents combination of 40% w/w potassium fluoride on alumina with Aliquat 336 appeared to be the most optimum reaction system in terms of yield and convenience. Lee et al. the PTC breaks the crystal lattice and transports the nucleophile as Q+Y− whose concentration depends on the type of PTC used. 10 min O-Ar 15 Scheme 8.340 P. The system elegantly forms a synergistic combination of S–L PTC and microwave irradiation. [113] showed that the treatment of phenols (14) with nitroaryl fluorides (15). This is a solid–liquid PTC process in which the entire catalyst is in the organic liquid phase.. and antipyretic drugs . tetra-n-butylammonium bromide (TBAB). Cl + 10 11 PTC/Solvent MW O O 12 + NaCl O ONa Scheme 7 O-alkylation of o-Hydroxyacetophenone under MW-PTC condition. the activity of TBAB is much greater. 18-crown-6. analgesic. tetra-n-propylammonium bromide (TPAB) and tetra-n-butylammonium iodide (TBAI). The type of cations and anions present in the system greatly influences the solubility of solid nucleophile. such as anti-inflammatory.A. They reported sluggish reaction for the same arylation reactions with KF-alumina/ 18-crown-6 in acetonitrile reaction system even when the reaction is allowed for 84 h. OH ArF R 13 14 KF-alumina/Alumina MW. In fact. TBAB was found to more efficient catalyst for the reaction under study. and KF-alumina) in microwave promoted arylation reactions. such as BTEAC. TBAI. In general. Mechanism for aromatic nucleophilic substitution reaction between p-chloronitrobenzene and ethoxide ion in the presence of PTC conditions.Recent Strategies in Phase Transfer Catalysis and its Application … 341 [114]. ecologically clean additives to motor oils. Further we have compared the reactivity of microwave-PTC assisted reaction with ultrasonicPTC assisted reaction and silent-PTC reaction (Table 6). TBAHS. the comparative reactivity’s of eight different phase-transfer catalysts. The order of the activities for these eight quaternary ammonium salts is TBAI< TBAB <BTEAB < TEAB < TBAC < BTEAC < TBAHS <TEAC. BTEAB. TEAC and TBAB was explored. TEAB. the order of the distribution of halide ions in the organic phase is I. In contrast. perfumery [118] and plasticizer [119]. which reflects the Starks’ extraction mechanism. In this nucleophilic substitution reaction. non-toxic and high-octane gasoline additives [115–117]. The corresponding kapp values in using these quaternary ammonium salts are depicted in Table 6.> Br. in the ethoxylation of p-chloronitrobenzene. EtOH + KOH in situ EtO-K+ + H2O EtO-K+ + Q+X(PTC) in situ KX EtO-Q+ + Quaternary ammonium ethoxide O Cl EtO-K+ + No2 16 Cl EtO-Q+ + No2 16 Aromatic nucleophilic substitution reaction Aromatic nucleophilic substitution reaction + No2 17 O + No2 17 KCl Q+X- Scheme 9.> Cl-. the order of the reactivities of the . p-nitrophenetole was synthesized by the reaction of p-chloronitrobenzene with potassium ethoxide in a homogeneous system using benzyltriethylammonium chloride (BTEAC. Kinetic results indicate that the microwave irradiation enhances the reaction.The mechanistic details of the reaction is presented in Scheme 9. TBAC. Q+Cl-) as a phase transfer catalyst at 50 0C under microwave irradiation conditions [120]. ethanol. which is a function of carbon in each chain.88 0.61 2.5 g. 50 0C.06 2.A.96 1.91 1.90 0.) TEAC 19. Influence of phase-transfer catalysts on the apparent rate constants. The yield of the product is correlated with the accessibility of the quaternary ammonium salt (Q+X-). agitation speed 600 rpm.86 1 . For the quaternary ammonium cations with the same halide ion (chloride and bromide).15 0.39 0.1 . The activity of the catalyst is dependent on the structural characteristics of a quaternary ammonium cation.00 0.42 1.79 17.Silent Cond. For an interfacial reaction mechanism. It is thus concluded that the order of the activities is consistent with the results indicated by Starks et al. Hence.1 .56 a Ultrasonic condition: 28 kHz. Thus. water. kapp: 8 g.Ultrasonic Cond.M. KOH.) kapp (x 10-2 min. [121].) kapp (x 10-2 min.84 2. the reaction rate is highly dependent on the concentration of the catalyst at the interface.71 18.W Cond.61 1. microwave condition . it is obvious that a higher reactivity is obtained for a quaternary ammonium salt of less total carbon number.342 P. This phenomenon is more consistent with the interfacial reaction mechanism rather than the extraction reaction mechanism. ultrasonic conditiona. 20 18 kapp x 10 (min ) 2 -1 16 14 12 10 0. the order of the activities of these PTC’s is TEA cation > BTEA cation > TBA cation. 0. 30 mL. p-chloronitrobenzene. silent condition. 200 W.23 1.29 TBAB 14.Vivekanand and Maw-Ling Wang tetrabutylammonium cation group was found to be TBAHS > TBAC > TBAB > TBAI. 15 min of reaction. 1 mL.67 - TBAI 13.05 0. PTC’s TEAB kapp (x 10-2 min.25 g. 0.73 14.96 TBAC TBAHS BTEAB BTEAC 16.95 2.20 Amount of BTEAC (g) . nonane.15. smaller size of the anionic ion in the halide groups of PTC’s is favorable for a high reaction rate.10 0. Table 6. ethers. Generally.at a higher concentration. A further increase in the amount of BTEAC makes the conversion of p-chloronitrobenzene decrease (Fig.5 g. Addition of catalytic amount of quaternary salt (Q+X-) accelerates the reaction rate to a great extent and selectivity of the reaction [133. At higher concentration of Q+Cl-. KOH. the extensive study of Heck-type reactions [130-132] and their application in organic synthesis has led to the introduction of various improvements [133-135]. Owing to its mild reaction conditions.124] (Scheme 10). the efficiency of which has interested organic chemists for a long time ago. This type of reaction is driven by the ability of Pd(0) complexes to undergo oxidative addition to C-X (X= Cl. water. the reaction is greatly enhanced by adding a small quantity of the BTEAC catalyst.126]. 15 min of reaction. 50 0C. Heck reaction is one of the most popular methodologies for carbon-carbon coupling in synthetic organic chemistry due to its high chemoselectivity and mild reaction conditions [122]. Olefins with variety of functional groups viz. 6). quaternary ammonium and phosphonium salts are used to help displacement from halides. 1 mL.[127].. esters.Recent Strategies in Phase Transfer Catalysis and its Application … Figure 6.135-147]. ethanol. 0. UV screens.1 g of BTEAC. i) cationic mechanism or and ii) a neutral mechanism [125. Hence. phenols. preparation of hydrocarbons. dienes. microwave condition. the neutral mechanism is operative when X is σ-donor such as Cl. and in advanced enantioselective synthesis of natural products [128].. The decrease is probably due to the fact that the conversion of potassium ethoxide to quaternary ammonium ethoxide reaches a new equilibrium state. the conversion of p-chloronitrobenzene is low. Influence of the amount of BTEAC on the apparent rate constants. the conversion of p-chloronitrobenzene is decreased with an increase in the amount of Q+Cl. or when Ag+. polymerization chemistry. An optimum value of the BTEAC catalyst corresponds to a 0. can be employed however allylic alcohols tend to rearrange [129]. Nonetheless. nitriles. p-chloronitrobenzene. On the other hand. carboxylic acids. 30 mL. 343 In the absence of BTEAC. Now a days. nonane. or I. Former type of mechanism is operative when the X is OTf. the equilibrium tends to shift to the formation of potassium ethoxide and thus the quaternary ammonium ethoxide is decreased by Le Chatelier’s principle. TI+. Br and I) bonds followed by addition to olefinic compounds [123. kapp: 8 g. Their mechanism are classified into two types viz. . the Heck reaction works best for preparation of di-substituted olefins from mono-substituted ones and electron poor olefins tend to give higher yields. Heck reaction is widely used in pharmaceuticals. 0. Br. HECK REACTION The formation of carbon–carbon bonds is a fundamental reaction in metal-catalyzed organic synthesis.25 g. OAc. CH2COOCH3 R2= CH3.344 P. Ligand. Heck reaction assisted by phase transfer catalyst (PTC) has been developed into an efficient methodology for coupling of aryl halides with alkenes leading to substituted alkenes. Cy2NMe DMAC.Vivekanand and Maw-Ling Wang H R2 18 R1 R3 R 4X 19 Pd(0). The Heck reaction is an important methodology for the introduction of functionalized aryl moieties onto heterocyclic compounds in organic synthesis. . Heat R1 R2 R4 3 R3 20 Scheme 10. Penalva et al. 85-100 0C Ar 27 EWG R1 EWG R1 = H. Modified Heck reaction using bulky amine bases in presence of tetrabutylammonium chloride. R1 EWG ArX 25 EWG ArX R2 28 26 Ar R2 29 26 1-4 mol % Pd(OAc)2 TBAC. [148] explored direct arylation of activated thiophenes (21) using a Heck type reaction with a mixture of Pd(OAc)2 and tetra-n-butylammonium bromide as catalytic system.A. Heck reaction between 2-cyanothiophene and iodobenzene. I NC S 21 22 "Pd" Base. Unexpectedly. General Heck Reaction. Ar X = Br. Base Solvent. In recent past. the reaction resulted in competitive formation of biaryls (24) resulting from an Ullmann type coupling (Scheme 11). I Scheme 12. PTC NC S 23 24 Scheme 11. When stoichiometric quantity of tetraethylammonium chloride is employed. MWI Ar Ar 32a-g 31 a = Ph(R). The following order illustrates the relative activity of different catalysts and bases: TBAB>TBAI>TBAC>PEG-400 & K2CO3>Na2CO3>NaHCO3>NaOH (Table 7). Bases such as N. Palladium and PTC catalyzed Heck cross coupling reaction under microwave irradiation.CH3C6H4(R). COOH(Y). Scheme 13. Nevertheless. [150]. Ph(Y). the yields of the microwave irradiation assisted reaction and conventional heating reaction results are summarized in Table 8. The method displays good stereoselectivity and a high degree of functional group compatibility. f = p-CH3C6H4(R). Even ortho-substituted aryl halides. Labeling studies indicate that the source of this selectivity is thermodynamic in nature. in these cases a greater quantity of catalyst was required. On the other hand. Ph(Y). including tetrabutylammounium chloride (TBAC).K2CO3 H2O. the behavior of the tetraalkylammonium salt is more dependent on counter ion nature than upon the alkyl chain length and only phase transfer agent bearing a bromide as the counter ion provides an active catalyst system than with other halide counter ions. tetrabutylammounium bromide (TBAB). Ph(Y). g = o. The arylation reaction of alkenes (30) with aryl iodides (31) proceeded smoothly under microwave irradiation to give exclusively the desired trans-products in good yield (Scheme 13). COOH(Y). e = o-O2NC6H4(R). tetrabutylammounium iodide (TBAI) and polyethyleneglycol (PEG). Ph(Y). whose transformations are problematic under typical reaction conditions. For comparison. the competitive formation of biphenyl is inhibited. the reaction proceeded with the shortest reaction times. N-diisopropylethylamine leads specifically to the biaryl formation.TBAB.Recent Strategies in Phase Transfer Catalysis and its Application … 345 The investigation reveals the influence of various parameters such as the nature of the base and the nature and/or the amount of the phase transfer agent on the reaction selectivity. d = p-O2NC6H4(R). were efficiently converted into the desired trisubstituted olefins under PTC condition. The results showed that the synthesis of compounds 32a–g under microwave irradiation were 18–42 times faster than . c = p-HO2CC6H4(R). b = Ph(R). COOMe(Y). Gürtler and Buchwald [149] successfully explored coupling of activated olefins (25 & 28) with both electron-rich and electron-poor aryl halide (26) substrates by employing the Pd(OAc)2/ Cy2NMe/tetraethylammonium chloride system(Scheme 12). Palladium-catalyzed Heck coupling reaction in water in the absence of any organic solvents using PTC-microwave technology was investigated by Wang et al. In presence of stoichiometric amount of tetrabutyl ammonium bromide or a stoichiometric amount of tetraoctylammonium bromide with potassium carbonate as base. They compared catalytic efficiency of PTC and various bases in the synthesis of stillbene using various onium salts. Y + 30 RI R Pd(PPh3)2Cl2. Isolated yield. using haloarenes (31) and vinyltrimethylsilane (33) as double bond equivalent (Scheme 14). PTC assisted palladium-catalyzed synthesis of unsymmetrical stilbene derivatives. .PR3 or without PR3 Ar'X.Vivekanand and Maw-Ling Wang conventional heating. Room Temp. PTC approach proceeds most efficiently when carried out in the presence of aqueous solution of sodium carbonate or hydroxide and catalytic amount of PT catalyst. Table 8. Jeffery and Ferberone [151] reported one pot synthesis of unsymmetrical (or symmetrical) trans-stilbene derivatives based on two sequential PTC-Heck-type reactions effected in the presence of tetrabutylammonium salt-based catalyst systems.346 P. Table 7. K2CO3 65-105 0C Ar' 34 Scheme 14. and stereoselective products. b. The procedure followed results in highly chemo-.Pd(dba)2. TBAC. Toluene. 2) removal of excess CH2-CHSiMe3 Ar 3)cat. This ratio between the reaction time using conventional reflux and microwave irradiation (tc/tmw) under same conditions quantifies the microwave heating effect. Influence of Catalyst (PTC) and Base on the Formation of 32aa Base K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 Na2CO3 NaHCO3 NaOH PTC No PTC PEG-400 TBAC TBAI TBAB TBAB TBAB TBAB Yield of 32ab 30 80 84 90 91 88 61 52 a-The reaction was carried out in H2O at a power level of 375W for 10 min under argon. DMF. regio-.A. Role of Microwave and Conventional Heating in the Heck product formation Product 32a 32b 32c 32d 32e 32f 32g Microwave heating (375 W) tmw(min) Yield (%) 10 91 10 88 10 92 10 89 10 86 10 89 10 93 Conventional Heating tc(min) Yield (%) 420 85 180 88 420 90 180 80 180 80 420 84 300 54 tc/tmw 42 18 42 18 18 42 30 SiMe3 33 ArI 31 1)cat. KF. This second step can be carried out either in presence or absence of phosphine ligand at room temperature (Table 9. in the presence of already present palladium catalyst and tetra-nbutylammonium chloride system and added potassium carbonate. Entry Ar-X (31) I Ar’-X (31’) I PR3/Pdb Temp (o C) Product (34) Ar' Yield [%][b] 90 60 (96) 72 (94) 66 (80) 60 (84) 72 (94) 1 MeO I Cl I 0 0 2 I 65 85 65 65 Ar Ar= 4-OMeC6H4 Ar'= 4-ClC6H4 Ar' Ar Ar= 4-ClC6H4 Ar'= 2-naphthyl Ar' 2 Cl I 3 Cl MeO I 0 Ar Ar= 4-ClC6H4 Ar'= 4-OMeC6H4 Ar' 4 S I 2 Br 85 Ar Ar= 2-thienyl Ar'= 2-naphthyl Ar' 5 S I N 2.4-trihydroxystilbene).5. Table 9. with a very high isomeric selectivity for the (E) configuration ranging between 96 and 99%. in the presence of potassium fluoride. In order to effect second Heck reaction the excess of vinyltrimethylsilane (33) was then removed under reduced pressure. highly chemo-. Comparative yields of unsymmetrical stilbene derivatives synthesized by Heck reaction. The authors further confirmed the potential and efficiency of the described methodology by a concise. Stilbene derivatives with a very high isomeric selectivity ranging between 95 and 99% were formed. tetra-n-butylammonium chloride and catalytic amounts of bis(dibenzylideneacetone)palladium (Scheme 14). Further. entries 4–6). of vinyltrimethylsilane (33) and were followed by arylation in wet DMF in the presence of palladium catalyst and tetra-n-butylammonium chloride (already present in the reaction mixture) and potassium carbonate (added). entries 1–3). heteroaromatic trans-stilbenes can be synthesized using this methodology (Table 9.Recent Strategies in Phase Transfer Catalysis and its Application … 347 Unsymmetrical trans-stilbenes (34) obtained in high yields by treating aryl iodide with an excess of vinyltrimethylsilane.Ndimethylformamide. and stereoselective synthesis of resveratrol (trans-3. The second Heck reaction was realized in wet N.5 I 105 Ar Ar= 2-thienyl Ar'= 4-N(Me)2-C6H4 Ar' 6 S I 0 MeO 65 Ar Ar= 2-thienyl Ar'= 4-OMe-C6H4 Similarly symmetrical stilbene derivatives were synthesized by treating of 2 equiv. with or without triarylphosphine. GC–MS analyses of the reaction mixtures indicated a nearly exclusive formation of stilbene derivatives. regio-. convenient. . of an aryl iodide (31) with 1 equiv. 1 2 3 4 5 6 7 8 PTC Benzyldimethyl 2-hydroxymethylammonium chloride Tetrabutylammonium fluoride Tetrabutylammonium iodide Tetrabutylammonium terafluroborate Tetrabutylammonium hydrogen sulphate Tetrahexylammonium bromide Benzyltriethylammonium chloride Tetrabutylammonium bromide Yield of 37b (%) 89 54 88 79 82 87 74 91 . Entry No. TBAB in H2O (Table 10). butyl(g) and tert-butyl amine(h) Scheme 15. Researchers are particularly interested in terminal aziridines due to their facile ring-opening with various nucleophiles [154]. [156] have developed a practical.A. Aziridinaton α-bromo-2-cyclopenetenone using PTC protocol Table 10. for example. azinomycins and mytomycins [152]. Effect of different some phase transfer catalysts on aziridination of -bromo-2cyclopenetenone in the presence of H2O at room temperature. H2O rt O H R H 37(a-h) N 35 36(a-h) R = phenylethyl(a). cyclohexyl(d). high reaction temperature and use of additives [155]. O Br RNH2 TBAB. For that reason.Vivekanand and Maw-Ling Wang AZIRIDINES Aziridines are organic compounds containing one amine group and two methylene groups and are constituents of several molecules presenting biological activity. difficulty of recovery of high boiling solvent relative to the stability of aziridines. allyl(e). These nitrogen-containing heterocyclic compounds are frequently show up as substructures in natural products and also show potent biological activities[153]. furayl(c). Most of the reactions gave similar results using various PTCs. In this regard PTC methodology is can be applied in the synthesis of aziridines. Rolf Carlson et al.348 P. use of toxic and organic solvent. benzyl(b). propyl(f). chemists would like to develop practical and convenient methods for constructing aziridine compounds. highly efficient and simple aziridinaton protocol for α-bromo-2-cyclopenetenone derivatives 35 (Scheme 15). Also they have assessed different reaction conditions to apply tandem conjugate addition initiated ring closure (CAIRC) reactions and reported the synthesis of N-substituted bicyclic-a-ketoaziridines (37) from a series of primary amines (36) applying eight different PTC’s particularly using tetrabutylammonium bromide. Synthesis of aziridines by conventional methods suffers from several disadvantages such as long reaction time. Cyclization of 3-Arylamino-2-chloropropane nitriles. Table 11. 1 Amine 35b Time (h) 5 Product O Yield(%) 93 37b N 2 35a 5 O 98 N 3 35c 5 37a O 91 o N 4 35d 3 37c O 90 N 37d 5 35e 3 O 96 37e N 6 35 h 3 O 97 N 7 35f 3 37h O 95 N 37f 8 35g 1 O 94 N 37g Further they examined the role of various aliphatic primary amines 35a–h (phenylethyl.Recent Strategies in Phase Transfer Catalysis and its Application … 349 Especially. the aziridination reactions mediated by benzyldimethyl-2-hydroxyethyl ammonium chloride. furayl. Hex4NBr and Bu4NBr (entries 1. . Bu4NI. 6 and 8. butyl and tert-butyl amines. obtained by the interaction of arylamines with α-chloroacrylontrile. allyl. benzyl. is an efficient method under PTC condition to prepare N-aryl-2-cyanoaziridines [157]. respectively) proceeded in a similar manner with good to excellent yields. cyclohexyl. propyl. Entry No. Particularly. the reaction of t-BuNH2 (35h) was very fast and the reaction was completed within 1 h. 3. Influence of various aliphatic primary amines on aziridination of -bromo-2cyclopenetenone in presence of TBAB. respectively) in the aziridination of α-bromo-2-cyclopenetenone under PTC condition and observed excellent reactivity with all the tested amines (Table 11). phase transfer catalysis in presence of nitrogen.Vivekanand and Maw-Ling Wang In general. aziridination. respectively. Recently. dichlorocarbene addition. ester alkylation and alkene epoxidation. Higher conversions and yields (80 and 85%) were reported by the authors by extending the reaction time to 15 and 24 h with salts TBAB and [39c][BF4]. In order to understand the partition ability.A. Researchers have seldom employed carbocations as phase transfer agent under such conditions. Catalytic efficiency (Scheme 17 & Table 12) of these triazatriangulenium Cations were compared with TBAB in aziridine reaction of styrene (40) with a mixture of Chloramine-T (41) and diiodine by following Minakata and Komatsu protocol [166]. they synthesized several triazatriangulenium cations bearing alkyl side chains of various lengths and polar/apolar character (Scheme 16) and followed various organic reactions viz. [39a] [BF4]-[39d] [BF4].6-dimethoxyphenyl)carbenium ion and primary alkylamines [159-164]. hydrophilicity and lipophilicity. The order of the activities for these catalysts after five hours of reaction : [39a][BF4] < [39b][ BF4] < [39d][ BF4] < [39c][ BF4] < TBAB. there is an upsurge in interest in catalytic community about utility of these triazatriangulenium ions as phase transfer agent. . Previous reports indicate the possibility of synthesis of stable carbocations [158]. R = (CH2)7CH3 Scheme 16. Synthesis of Triazatriangulenium Salts. Stable carbocations and triazatriangulenium ions were synthesized starting from tris(2. R = (CH2)OH 39b. R = (CH2)CH3 39c. Nicolas and Lacour [165] explored its utility in several classical PTC reactions and compared their efficiency to that of tetrabutylammonium bromide and 18-crown-6.and phosphorus-based catalysts is carried out under strongly basic and nucleophilic conditions.350 P.. Hence their utility under these strenuous conditions is well understood. MeO OMe + O O MeMe 38 [BF4] OMe OMe R-NH2 (excess) 170-180 oC R N + N R 39 [BF4] N R 41% 40% 44% 44% 39a. R = (CH2)5CH3 39d. Minakata et al. 2 h O N Cbz 44 44: 80% NaCl PhCH2N+Et3 Cl- Cl O N _ Cbz _O Cl N Cbz PhCH2N+Et3 PhCH2N+Et3 Scheme 18.Cbz (44 ). was followed by using 10 mol % of BTEAC under solid–liquid phase-transfer catalysis condition. Aziridinaton of styrene (40) with chloramine-T (41) using PTC protocol.Recent Strategies in Phase Transfer Catalysis and its Application … 351 C6H5 + 41 40 Ts O Cl cat. Mechanism of aziridination of methyl vinyl ketone (43a) and chloramine. I2 N S N Na O CH2Cl2 :H2O C6H5 20 0 C 42 Scheme 17.(10 mol%) MeCN. afforded the aziridine product .(10 mol%). Table 12. Entry 1 2 3 4 5 6 7 8 Catalyst TBAB [39a][BF4] [39b][BF4] [39c][BF4] [39d][BF4] TBAB [39c][BF4] no Time(h) 5 5 5 5 5 15 24 5 Yield (%) 30 5 7 23 16 80 85 3 Conversion (%) 37 7 9 28 20 95 100 5 + O 43a (2 equiv) Cl N Na Cbz PhCH2N+Et3 Cl. [167] developed a simple synthetic method for the catalytic aziridination of electron deficient olefins with N-chloro-N-sodio benzyl carbamate based on solid–liquid phase-transfer catalysis using BTEAC as phase transfer agent.Cbz (44). RT. Aziridination of Styrene by Chloramine-T/I2 under PTC condition. Aziridination reaction between methyl vinyl ketone (43a) and chloramine. 352 P. Entry 1 2 3 4 5 a EWG MeO O Ph S O O O O O O O O N O N O N O R1 H H H Me CO2Et Equiv. Resulting in high yields (Scheme 19 & Table 13).Cbz (44) is exchanged for an ammonium ion. yielding optically-active aziridines with an enantiomeric purity of up to 87% ee.Cbz (44). Influence of various electron-deficient olefins in the aziridination reactions. BTEAC catalyzed aziridination of electron-deficient olefins (43) with chloramine. Further. even in presence of only 1 equiv. with an oxazolidinone auxiliary. EWG 43 R1 + Cl Cbz N Na 44 BTEAC MeCN. Table 13. The successfully extended this protocol to Methyl acrylate (43b) and phenyl vinyl sulfone (43c).Vivekanand and Maw-Ling Wang in 80% yield in 2 hours and for this reaction they proposed a rational mechanism. of 43 EPOXIDATION Epoxidation of olefins is one of the most important reactions in organic synthesis as the epoxides are useful intermediates in the manufacturing of a variety of chemicals. Developing new catalysts that will utilize environmental friendly oxidants for alkene epoxidation as an . was found to be a good substrate for the aziridination reaction.a 2(43b) 2(43c) 1(43d) 2(43e) 1(43f) Cat (mol%) 20 20 10 10 10 Time/h 24 4 4 24 24 yield (%) 85 89 93 60 58 Equiv.A. RT EWG 45 N Cbz R1 Scheme 19. the sodium ion of chloramine. subsequent Michael addition of the soluble nitrogen species to the enone gives the enolate and finally intramolecular cyclization affords the desired aziridine (Scheme 18). Unexpectedly. of 43d. they explored asymmetric reactions by using chiral ammonium salt catalysts derived from cinchona alkaloids. Initially. Olefins 43e and 43d afforded products in 60 and 58% yields respectively. and Aliquat 336. viz.3 Q3PW12(O)n-1O40 + H2O2 kQPWO k1 Q3PW12(O)n-1O40 + C8H14O Q3PW12(O)nO40 + C8H14O k2 Q3PW12(O)n-1O40 + C8H14O2 Organic Phase Scheme 21. Epoxidation of olefins is a classical PTC operation and has been the theme of numerous synthetic and mechanistic studies in the recent past [171-180].7-octadiene under PTC conditions. Kinetic study of ultrasound assisted phase-transfer catalyzed epoxidation of 1. are the rate-controlling steps to produce two products.Recent Strategies in Phase Transfer Catalysis and its Application … 353 alternative to the stoichiometric oxidation processes still continues to be a subject of interest [168-170]. C) O Scheme 20.7-octadiene under PTC conditions. A) 46 (C8H14O.2 H3PW12(O)nO40 + 3QCl Interface Q3PW12(O)nO40 + H2O kQPWO Q3PW12(O)nO40 + C8H14 ka. Epoxidation of 1. Aliquat 336 Phosphotungstate Acid Hydrogen Peroxide 45 (C8H14. B) O O 47 (C8H14O. Mechanism of epoxidation of 1. An active intermediate of the catalyst (Q3PW12(O)nO40.2. ..7.7-octadiene is greatly enhanced by using a cocatalyst of phosphotungstic acid in the presence of hydrogen peroxide in an organic solvent/aqueous solution two-phase medium [61].8-diepoxyoctane. where Q = R4N+) produced from the reaction of phosphotungstic acid. 1. a rational mechanism is proposed as follows: nH2O2 + H3PW12O40 ka.2-epoxy-7octene and 1. including two series reactions.1 Aqueous Phase H3PW12(O)nO40 + nH2O Q3PW12(O)nO40 + 3HCl ka. The organic-phase reactions. hydrogen peroxide. For that. A. providing for the epoxidation.354 P. and tetrahexylammonium chloride (THAC). the overall reaction involves the ion exchange. Thus.Catalytic activity of these onium salts indicate that their efficiency in the epoxidation reaction depends primarily on two factors viz. Actually. The main reason is that the organic-phase reaction is the rate-controlling step. kQPW = mass-transfer coefficient of Q3PW12(O)n-1O40. only one oxygen. Therefore.3 = third intrinsic rate constant in the aqueous solution. we found that the reactivity of Aliquat 336 is obviously larger than that of THAC because of the lack of unsymmetry in the alkyl groups of the quaternary ammonium cation. The steric hindrance for an unsymmetric quaternary cation is small when it is used to attack the double-bond compounds. (Table 14) .2 = second intrinsic rate constant in the aqueous solution. Then.There are many active oxygens for this active intermediate of the catalyst. the ion-exchange reaction of Q+(X-) with H3PW12O40 takes place in the aqueous phase to form a complex that is ready to transfer to the organic phase through the . The kinetic investigations reveal that those quaternary ammonium salts with larger total carbon numbers possess higher catalytic reactivity. which is a real oxidant. We compared the catalytic efficiency of various commercial PTC’s in the epoxidation of 1.e. which participate in the formation of the active intermediate of catalyst. supplies 1. Hence. and the mass transfer of catalyst between two phases.7-octadiene. prefer to stay in the organic phase. k1 = first intrinsic rate constant in the organic solution. an active intermediate H3PW12(O)nO40. In comparison with the reactivity of these two quaternary ammonium salts. almost no reaction occurs in using TEAC as the phase-transfer catalyst in the epoxidation of 1.1 = first intrinsic rate constant in the aqueous solution. the epoxidation of 1.Vivekanand and Maw-Ling Wang where ka.7-octadiene. tetraethylammonium chloride (TEAC). was formed from the reaction of phosphotungstic acid and hydrogen peroxide in the aqueous phase. Mechanistically. Aliquat 336 and THAC have almost the same total number of carbon atoms in the quaternary ammonium cation. the organic-phase reaction.7-octadiene. which can be transferred to the interface for regeneration to produce the active intermediate of the catalyst.7-octadiene involves several steps.state rate law is sufficient to describe the kinetics of epoxidation of 1. In addition.trioctylmethylammonium chloride (Aliquat 336). C). the order of reactivity of TBAI. and TBAC is TBAI > TBAB > TBAC. i. kQPWO = mass-transfer coefficient of Q3PW12(O)nO40. TBAB. B and C8H14O2. First. A pseudo steady. the active intermediate of the catalyst is reduced to Q3PW12(O)n-1O40. A) to form the epoxides (C8H14O.7-octadiene in using phosphotungstic acid as the cocatalyst. However. ka.. the concentration of the active intermediate of catalyst in the organic phase is increased with an increase in the total carbon numbers of the quaternary ammonium cations. The quaternary ammonium salts used in this study include tetrabutylammonium bromide (TBAB). these quaternary ammonium salts unsymmetric cation possess high reactivity. tetrabutylammonium chloride (TBAC). the complex reaction in the aqueous phase. k2 = second intrinsic rate constant in the organic solution. which is organic soluble. and n is the number of peroxo oxygen atom with tungsten metal (W = O) firmed between the reaction of hydrogen peroxide (H2O2) and phosphotungstic acid (H3PW12O40). Those larger total carbon number quaternary ammonium salts. transfers to the organic phase and reacts with the organic-phase reactant (C8H14. ka. i) total number of carbons in the salt and reactivity of halides. An ionexchange reaction that took place between this real oxidant and phase-transfer catalyst to form the active intermediate of the catalyst Q3PW12(O)nO40 at the interphase between two phases. this active intermediate of the catalyst Q3PW12(O)nO40.. Hence. 7.35 TBAI 1.09 x 10-3 mol of 1. resulted in excellent selectivity for the epoxide. Therefore. kapp. limnone cyclooctene cyclohexene. we examined the role of Aliquat 336 and the H3PW12O40 (cocatalyst) in the epoxidation of 1.54 73.2.31 0.2. These three quaternary ammonium salts have the same total number of carbon atoms in the quaternary ammonium cation. PTC TEAC 0 0 kapp1 (x 10-3min-1) kapp2 (x 10-3 min-1) tB. In epoxidation. PTC assisted epoxidation of cyclooctene gave only the epoxide with near quantitative yields. the reaction is enhanced only in the presence of both Aliquat 336 and the active cocatalyst H3PW12O40 To examine the influence of ultrasonic irradiation on the conversion of 1.octadiene. In contrast. 1000 rpm.77 x 10-4mol mol of quaternary ammonium salt. at lower substrate: oxidant ratio. Selective epoxidation of alkenes (norbornene.46 THAC 3. we compared the conversion of 1.7octadiene is low in using sodium tungstate and phosphoric acid as the cocatalyst.Recent Strategies in Phase Transfer Catalysis and its Application … 355 interface. the epoxidation is still low only by hydrogen peroxide oxidation. 9. the iodide ion (I-). leading to the formation of the active intermediate of the catalyst. without ultrasonic irradiation the conversion of 1. which possesses higher activity. However. 7.max because of its higher reactivity. it is found that the conversion of 1.23 x 10-2 mol). even at ambient temperature conditions and shows no tendency to undergo allylic oxidation or cleaving of the epoxide like cyclohexene (Table 15).72 1014.92 x 10-4 mol of H3PW12O40. cyclohexene.7-octadiene. gave a mixture of both cis-stilbene oxide (88% selectivity) and trans-stilbene oxide (balance) as products at the maximum conversion of the substrate (conversion: 57%).7-octadiene is only 76%.max (min) TBAC 0. cyclohexene chiefly underwent allylic oxidation while .47 Aliquat 336 20. Epoxidation of norbornene and cyclohexene. The order of the selectivity constants K(X-) is K(I-) > K(Br-) > K(Cl-) [121]. 5.7-octadiene. the conversion of 1. The active intermediate of the catalyst H3PW12(O)nO40.2 1. 9. are shown in Table X. Obviously. The two corresponding apparent rate constants. Influence of the quaternary ammonium salts on the conversion of 1.7octadiene: 35 ml of H2O2 (8%. However. prefers to exchange with the phosphotungstic ion. another activated alkene.24 x 10-3mol of biphenyl. respectively. 1. Without the addition of a cocatalyst. Epoxidation of cis-stilbene. 200 W). 50 0C.24 2545.02 524.6 0. TBAI exhibits higher reactivity among these three quaternary ammonium salts.1 and kapp.7-octadiene is also low in the absence of Aliquat 336 and phosphotungstic acid or by individually using each compound.80 0. 32 ml of chloroform. and a smaller value of tB. is not effectively transferred to the organic phase in the absence of Aliquat 336. Aliquat 336 possesses higher values of kapp. but in the presence of ultrasonic the conversion is 97% and almost 100% for 28 kHz and 40 kHz. As shown in Fig.1 and kapp. styrene and cis-stilbene) with aqueous H2O2 as the oxidant in presence of Na9[SbW9O33] -methyl tricapryl ammonium chloride system was investigated by Ingle and Raj under solventless condition [181]. At 120 min.7-octadiene in silent and ultrasonic conditions. which only stays in the aqueous phase.39 1752. on increasing the substrate: oxidant ratio. ultrasound conditions (28 kHz.25 TBAB 0. 3.26 8.71 Further. Table 14. However a higher amount of Aliquat 336 does not increase the amount of the active catalyst to enhance the . The results indicate that the degree of epoxidation of HTPB increases from 5. By using a fixed amount of phosphoric acid and ammonium tungstate hydrate. ultrasound conditions (28 kHz. In the case of limonene.76 mmol.2-oxide was the only product obtained. 1. 50 0C. 1000 rpm. [188] investigated PTC assisted epoxidation of hydroxyl-terminated polybutadiene (HTPB) via using H2O2 as the oxidant and ammonium tungstate hydrate and phosphoric acid as the cocatalysts in an acidic solution/organic solvent two-phase medium. Terminal alkenes are normally very less reactive but with this catalytic system.356 P. the amount of the catalyst was varied at constant amount of phosphoric acid and ammonium tungstate hydrate. Figure 7. the amount of the synthesized active catalyst was also maintained at a fixed value. which possesses high reactivity to catalyze the epoxidation of olefins.77 x 10-4 mol of Aliquat 336.92 x 10-4 mol of H3PW12O40.09 x 10-3 mol of 1.A.7-octadiene. stereoisomers of limonene-1. Hydroxyl-terminated polybutadiene (HTPB) is widely used as fuel binder in composite solid propellants and adhesives and sealants [182-187].3% to 47.7% with the increase in the amount of Aliquat 336 up to 0. 32 ml of chloroform. 9.24 x 10-3 mol of biphenyl.23 x 10-2 mol).44 x 10-3 mol of Na2WO4. 1. 3. Effect of the phase-transfer catalyst and cocatalyst on the conversion of 1. 5. To explore the influence of Aliquat 336 on the kinetics of epoxidation of HTPB. 1-octene gave a moderate conversion of 38% and showed >99% selectivity for the epoxide.Vivekanand and Maw-Ling Wang norbornene gave norbornanone. 2. A further increase in the amount of Aliquat 336 does not improve the reactivity.88 · 1013 mol of H3PO4. 9.7-octadiene: 35 ml of H2O2 (8%. This is because of the active catalyst Q3{PO4[W(O)(O2)2]4} (Q+ was the quaternary cation). Wang et al. 200 W). PTC: 0. ratio (0C) 1:1 5 60 1:2 1:1 5 6 60 35 Conv. the molar ratio of Aliquat 336 to (NH4)5H5[H2-(WO4)6]·H2O).Recent Strategies in Phase Transfer Catalysis and its Application … 357 reactivity. (%) Selectivity (%) 5 5 6 Norbornene epoxide (80) norbornanone (20) Norbornene epoxide (11) norbornanone (89) Cyclohexene epoxide (25) Cyclohexene-2-ol (41) Cyclohexene-2one (34) Cyclohexene epoxide (92) Cyclohexene diol (8) Cyclooctene epoxide (>99) Cyclooctene epoxide (>99) cis-stilbene epoxide (88) trans-stilbene epoxide (12) 1-Octene epoxide (>99) 4 5 6 7 8 Cyclohexene Cyclooctene Cyclooctene cis-stilbene 1-Octene 1:0. R = CH2CH2CH2OH.(49) and methyl α -Daltropyranoside-based (50) chiral crown ethers. Oxidation of various alkenes over Na9[SbW9O33] + PTC with aqueous H2O2 as oxidant at different temperatures and different substrate: oxidant ratios.:aqu. [189] synthesized various novel. They investigated the catalytical potential of these crown ethers by following epoxidation of trans-chalcone with tert-butyl hydroperoxide . Optimum condition for the reaction was found to be 3:2. a 1ml toluene was used as solvent OCH3 O S S O O OCH3 O R S O N R O O O N R O O OCH3 O S R O N R O O O O O O O O O 48 49 50 Scheme 22. Table 15. methyl α -D-mannopyranoside. Mako et al.(48).01 mmol. substrate: catalyst ratio (500:1). Entry No. optically active crown ether derivatives from α-D-altropyranoside (Scheme 22).09 mmol. Substrate 1 2 3 Norbornenea Norbornenea Cyclohexene Sub.5 1:1 1:2 1:2 1:2 6 6 9 6 9 35 60 35 60 60 6 6 9 6 9 Reaction conditions—Na9[SbW9O33]: 0. H2O2 Time (h) Temp. Methyl α -D-glucopyranoside. In contrast. t-BuOOH toluene. Epoxidation of substituted chalcones with tert-butyl hydroperoxide using crown catalyst.20%NaOH 51 O H O H 52 Scheme 23. The lowest enantioselectivities were obtained in the case of ortho-substituted model compounds and the highest ee values were found in the case of para-substituted models ortho-substituted model compounds (Table 16). 3chlorophenyl-. the products 54h-k were obtained in 65–71% yields and the ee values increased according to the position of the chloro-substituent: the 2-chlorophenyl-. 79%. and 97%. aq. Epoxidation of trans-chalcone with tert-butyl hydroperoxide using novel. and 4-chlorophenyl products were obtained in an ee of 69%. aq. and α-D-altropyranoside-based chiral crown catalysts. . entries 2–4). while the ee values were in the range of 84–95% (Table 16. Authors reported a similar trend in the case of methoxy-substituents 54e-g. Also the study explains the importance of the position of the substituents in the aromatic ring of the chalcone on the chemical yields and enantiomeric excesses. the yields were 58–77%. O catalyst. This Indicates the influence of absolute configuration of the crown-ring fused carbon atoms of the monosaccharides on the enantioselectivity.6-O-benzylidene-α-D-glucopyranoside. In the presence of catalyst 1. practically no asymmetric induction was noticed. O Ar' 53 catalyst. t-BuOOH toluene. In the chlorophenyl epoxyketones cases. epoxidation of substituted chalcones and chalcone analogues (53) with tertbutylhydroperoxide catalyzed by the chiral monoaza-15-crown-5 lariat ethers annellated to methyl-4. entries 5-7). The investigation revealed a significantly different asymmetric induction by αD-glucopyranoside-.donating methyl-substituent afforded products 54b–d in better yields (72–90%) and the ee values increased according to the position of methyl group (71%.358 P. Chalcones with electron. Recently. when altropyranoside-based crown (50) is employed as catalyst. respectively) (Table 16. α-D-mannopyranoside-. Molecular modeling (MCMM) and subsequent DFT calculations indicate that the use of mannopyranoside based crown ether (49) and that of glucopyranoside-based catalyst (48) results in the preferred formation of the opposite antipodes of the corresponding epoxyketone.Vivekanand and Maw-Ling Wang (Scheme 23).or mannopyranoside have been investigated [190] and the results indicates significant asymmetric induction (Scheme 24).A. and 92%. 87%. optically active crown ether (50) as catalyst.20%NaOH Ar' O O R 54 S Scheme 24. . Entry 1 2 3 4 5 6 7 8 9 10 11 12 13 Product 54a 54b 54c 54d 54e 54f 54g 54h 54i 54k 54l 54m 54n Ar’ Ph 2-CH3-Ph 3-CH3-Ph 4-CH3-Ph 2-CH3O-Ph 3-CH3O-Ph 4-CH3O-Ph 2-Cl-Ph 3-Cl-Ph 4-Cl-Ph 2-NO2-Ph 3-NO2-Ph 4-NO2-Ph Time(h) 1 4 2 2 8 2 3 3 2 2 1 1 2 Yield (%) 82 72 90 81 69 77 58 65 68 71 66 55 63 ee (%) 94 71 87 92 84 88 95 69 79 97 80 >99 96 The ultrasound irradiation assisted epoxidation [191] of chalcones with aqueous sodium hypochlorite catalyzed by benzyldimethyltetradecyl ammonium chloride afforded 2.3-epoxyl1.025 mol equivalent catalyst to 0. Effect of substituents in chalcone on the asymmetric epoxidation in the presence of chiral crown ether 1 at 0–2 0C. On increasing the amount of benzyldimethyltetradecyl ammonium chloride from 0.8 40-44 93 a.Reaction time: 2 h. only 6% yield was observed (Entry 4.8 40-44 6 5 0.05 1:1. Table 16). Influence of temperature and catalyst concentration on the epoxidation of benzalacetophenone with sodium hypochlorite catalyzed by PTC under ultrasound irradiationa.Epoxidation of chalcones with electron-withdrawing nitrosubstitutent afforded epoxyketones 54l-n in 55–66% yield with high (80–99%) ee values(Table 16. entries 11–13). Table 17.05 1:1. the higher the extent of enantioselectivity.5 30-34 79 3 0. Table 17).05 1:1. On increasing the temperature to 30–34 0C or 40–44 0 C.8 40-44 84 6 0. hence the further the substituents are placed from the reaction center. the yield of epoxidation of benzalacetophenone increases to 79% and 83%.05 mol equivalent.Recent Strategies in Phase Transfer Catalysis and its Application … 359 respectively (Table 16. entries 8–10).5 22-26 48 2 0.3-diaryl-1-propanones in good yield. to 93% (Entry 6.05 1:1. In the absence of PTC. Table 16. the yield of epoxide increases from 84% (Entry 5. Table 17). Table 17).025 1:1. respectively (Entries 2 & 3.5 40-44 83 4 0 1:1.The substituents close to the reaction center prevent the asymmetric induction. Temperature Yield(%) Entry Amount of Substrate/NaClO(mol) PTC(mmol) 1 0. and MW conditions [205].2 71.39 An environment friendly method was developed for the alkylating esterification of 1hydroxy-3-phospholene oxides under solventless. The higher frequency resulted in a larger sonic resistance and loss of energy during the sonic waves propagating through the medium. The initial reaction rate generated by 0. At 200 W. Table 18. kapp = 0.A.75 equiv and by a factor of only 2.3 69.0150 min-1).08 1.Vivekanand and Maw-Ling Wang ESTERFICATION In last decade.0215 min-1).50 1. in the absence of any solvent at 100 0C using .35 1.3% (300 W. The product yields were 65. of potassium carbonate.8 in kapp(10-2 min-1) 1. kapp = 0.2% (300 W.5% (300 W. Yang and Peng [203] reported the esterification of sodium salicylate to synthesize butyl salicylate catalyzed by TBPB under ultrasound irradiation in a continuous two-phase-flow reactor. The effect of power of ultrasound on the reaction was performed at a frequency of 28 kHz.3 64.4 on increasing the catalyst loading to 0. kapp = 0. Entry No.2% (300 W. 78.1 78.360 P. kapp = 0. They investigated the effects of power and frequency of ultrasound on the third-liquid catalyzed esterification (Table 18). a great number of esters have been synthesized using the phase transfer catalysis methodology [192-202].1 equiv. 71.0135 min-1). decreasing with the increase of ultrasonic frequency. 50 kHz.0148 min-1) and 69.1% (silent. The MW-promoted alkylations were carried out in solid–liquid phase in the presence of 1 equiv.8 when 1. 28 kHz.12 2. kapp = 0.48 1. 80 kHz.5 71. TBAB plays a dual catalytic role in PTC esterifications of BIIR by rendering carboxylate anions nucleophilic and by isomerising exoallylic bromide into more reactive BrMe electrophiles [204].15 1. PTC methodologies are used to activate carboxylate nucleophiles for the purpose of preparing ester derivatives of brominated poly (isobutylene-co-isoprene) (BIIR). phase transfer catalytic. 1 2 3 4 5 6 7 Power (W) 0 300 300 300 300 100 200 Frequency(kHz) 0 28 40 50 80 28 28 Product Yielda organic exit (%) 65. Effect of ultrasonic frequency and power on the esterfication of sodium salicylate. catalyst was improved by a factor of 2. 40 kHz.2 69. the kapp was found to be 0. The sensitivity of reaction rates to TBAB concentration is examined by the authors.5 equiv of TBAB was employed.0108 min-1A high power of ultrasound offers much energy into the medium to enhance the reaction. The results reveal that catalytic amounts of the catalysts do support an efficient process and that higher levels have a relatively small effect on reaction velocities.0112 min-1). Knowledge of reaction fundamentals are used to prepare copolymers from BIIR and carboxylate-terminated polybutadiene (cBR) that phase-partition in the manner required for blend compatibilization applications. at 100 W the kapp was found to be 0.0139 min-1. 71. Scheme 25. the yields were significantly higher in the presence of 5% of TEBAC. Esterification of 1-Hydroxy-3-methyl-3-phospholene 1-Oxide (55) by alkylation at 100 C in the presence of K2CO3. 73. n-butyl (56d). 90. and benzyl (56e) esters were obtained in 80. the esterfication with reagents of normal reactivity may be promoted by the use of TEBAC. and 10). the ethyl (56a). 7. entries 1.c 1b. nBu(e). and 92% yield.Recent Strategies in Phase Transfer Catalysis and its Application … 361 different alkylating agents viz. phase transfer catalytic and MW conditions. respectively (Table 19. 69.. 8. entries 2. I R=Bn(a) Et(b). In the absence of triethylbenzylammonium chloride (TEBAC). in the above order. 4. However in the presence of 5% of TEBAC. n-propyl bromide. nPr(c). + P HO O 55 K2CO3/TEBAC RX MW. and 9). (Table 19. benzyl bromide.c Yield (%) 73 90 80 94 42 65 69 96 92 94 64 89 85 87 aThermal heating. and 94%. 3.c 1b 1b. Table 19. Entry No. The authors reported that except in the case of benzyl bromide. 94.c 1b. respectively.c 1b. . ethyl iodide. n-propyl (56b). Thus. all reactions went to completion and the yields were. isopropyl bromide and n-butyl bromide (Scheme 23). iPr(d). 96.5d 1b 1b 1b. Esterification of 1-hydroxy-3-phospholene oxides under solventless.c 1b. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 RX PrBr EtI EtI n PrBr i PrBr i PrBr n BuBr n BuBr BnBr BnBr n BuBr n BuBr BnBr BnBr n TEBAC 5% 5% 5% 5% 5% 5% 5% Mode of Heating MW MW MW MW MW MW MW MW MW MW Δa Δa Δa Δa Irradiating Time/Heating Time(Hours) 1b 1b 1b 1b. 100 0C RO P O 56 X= Br.c 1. Uncatalyzed thermal reaction of hydroxyphospholene oxide with n-butyl bromide and benzyl bromide. aziridine reaction. respectively (Table 19. or by the use onium salts with multi active sites. ultrasound and microwave irradiation. 14). However. The salient advantages of this green technology are easily recognized in the examples given. esters 56d-e were obtained after 1 h in 64 and 85%.. respectively (Table 19. expanding the applicability of phase-transfer catalysis in modern organic synthesis. The comparison is very encouraging for future applications of these techniques in conjunction with PTC. resulting in improved yields (5–7%) (Table 19. catalytic system. 13. ultrasonic frequency and microwave power. PTC catalyzed reactions belong in the toolbox of each synthetic organic chemist and have been used in many fields of organic synthesis leading to products of various interests. We have presented in this chapter some recent trends in the PTC catalyzed reactions viz. A vast array of experimental parameter’s. This can be achieved by optimizing reaction conditions by the use of ingenious new analytical techniques viz. At present. bases. the kinetic details of many PTC in conjunction with microwave/ultrasonic assisted reactions remain obscure.Vivekanand and Maw-Ling Wang Further. Improvements in reaction kinetics are expected with the advent of more systematic kinetic studies under these PTC conditions. for comparison purpose..362 P. On the other hand. some of the above reactions were also carried out under thermal conditions. epoxidation and esterfication that highlight the efforts and interest in developing more efficient processes according to the new requirements of the chemistry of the 21st century. viz. entries 12 and 14). 8 vs. entries 11 and 13). Still there is an urge in their minds to find more and more methods that augment their catalytic activity. substrates. both alkylations were essentially completed as the isolated yields were 89 and 87%. CONCLUSION Nowadays.A. The MW-promoted esterifications were more efficient than the thermal variations. 9 vs. temperature. . solvent. in the presence of 5% of TEBAC. Due to continuous improvements brought about by the advancements in the PTC technology. Ingenious new analytical and experimental techniques in conjunction with PTC have been compared with conventional PTC techniques. The development of PTC process in conjunction with various types of technologies delivers not only higher reactivity and stereoselectivity but also new synthetic opportunities. influence on optimum reaction conditions have been outlined. and 10 vs. Heck reaction. the alkylation reactions. continuous growth of PTC can be accelerated further only by the practicing chemists who will use the same brilliance and creativity that is the long tradition of catalysis and use it with the new perspective for transformative innovations for sustainability. The chapter supports the growing importance shown by researchers for highly active onium salts with multiple number of active-sites. Special features and mechanistic aspects are presented which helps us in understanding the practical value of this catalytic methodology. it can be predicted that how practical applications of PTC’s can be further expanded in the future. entries 7 vs. 12.. 11. Maruoka. A. N. A. P. A: Chem. 5367. T. Belokon’.. 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[195] Yang. Parent. [194] Yang.. Mol.A. Org. 3. [196] Pirkle W. Hegedüs. 39.. P. 15. 17. S. 919. S. G. .Sonochem. W. [203] Yang.. Ultrason. E. 48. Meijer. 2008. 206. [205] Bálint.. Keglevich. Catal. R. Appl.129. van den. M. Á.I. Chem. J. 2000. Keurentjes. 2003. A: Gen.H. E. H. S.. L.T.. H. P. S... C...M. AIChE J. . Poehler ISBN: 978-1-61122-894-6 ©2011 Nova Science Publishers. The major disadvantages of the use of heterogeneous catalysts in this case are the low selectivity of the process (in the case of hex-3-enoic acid derivatives there is essentially no selectivity) and the use of sorbic acid itself is impossible. specifically cis-hex-3-en-1-ol and trans-hex-2-en-1-ol. Instead salts or preferably methyl or ethyl esters are used. Details of the preparation of these compounds by hydrogenation using heterogeneous catalysts are given elsewhere [1-4].trans-hex-2. The use of homogeneous catalysts opened new possibilities to carry out the hydrogenations and significantly higher selectivities of formation of the desired products. aldehydes and acids are widely used in perfume chemistry.4-dienoic acid). can be obtained in various mixtures. it is a component of geraniol. Departement of Organic Technology. Inc. As stated above hexenoic acids and alcohols have very interesting fragrant properties. lavender and brandy mint oil. These compounds can be prepared by selective hydrogenation of the sorbic alcohol obtained for example from the chemical reduction of sorbic acid. From hexenoic alcohols the most commonly used compounds of this type are the socalled “leaf alcohols”. it is added to flower aromas (lilac for example) and . The easiest method for the preparation of hexenoic acids from the point of view of selectivity and simplicity is the selective hydrogenation of easily available sorbic acid (trans. Czech Republic INTRODUCTION Some C6 unsaturated alcohols. Depending on the catalyst used different regio and stereoisomers. Chapter 11 HEXENOIC ACIDS AND THEIR DERIVATIVES – PREPARATION USING SELECTIVE HOMOGENEOUS CATALYSTS Libor Červený and Eliška Leitmannová Institute of Chemical Technology. The titling of the two hexenols as leaf alcohols is partly reflective of their smell – their fragrance resembles that of freshly cut grass.In: Homogeneous Catalysts Editors: Andrew C. Perfumers [5] define their fragrance a little more precisely: cis-hex-3-en-1-ol is specified by its intense smell of fresh grass. introducing another step to the process. salts).and hex-3-enoic acid was accounted for by rearrangement of the intermediate [9]. The active species of the catalyst was the hydride [CoIII(CN)3H]3-. In subsequent work [8] the selectivity was more precisely specified. transHex-2-en-1-oic acid has a warm fruit aroma after dilution. 4 addition) both the cis and trans isomers can be formed. .: trans-hex-3. 3 or 4 to the one of the double bonds of sorbic acid is defined as regioselective hydrogenation. Synchronic formation of both 2. The fragrant properties of hexenoic aldehydes are also very interesting for the perfume industry but the simplest method of preparation (aldol condensation) was not superseded by hydrogenation due to the low stability of aldehydes. The authors of this work proposed that the hydrogen is not transferred in pairs and the π-coordination of the olefin is not realized before hydrogen transfer. In this type of reaction the trans configuration of the other double bond is preserved. The following chapters detail the progress in the development of homogeneous organometallic catalysts for the selective hydrogenation of sorbic acid and its derivatives (esters.1 MPa at a 3.: trans-hex-4-enoic acid was 82 : 17 : 1. It is also used for a refreshing orange aroma and it is a component of artificial geraniol and lavender oil.3:1 substrate: catalyst ratio in aqueous solution. It is used as an imitation of raspberry or in many other fruit aromas that require a caramel-acid note. The ratio of hexenoic acids was determined using gas chromatography. The mechanism of the reaction is shown in Figure 1. trans-Hex-2-en-1-ol has in low notes a strong fruit smell (chrysanthemum or wine). ORGANOMETALLIC COMPLEXES BASED ON COBALT The first homogeneous catalyst used for the hydrogenation of sorbic acid [6]. The reaction was carried out at room temperature with a hydrogen pressure of 0. Sorbic acid was added as its K+ salt and was selectively hydrogenated to the corresponding salt of trans-hex-2-enoic acid. up to 95 %. When the hydrogen is added to positions 2 and 5 (generally called 1. HOMOGENEOUS HYDROGENATION OF SORBIC ACID AND ITS DERIVATIVES The homogeneous hydrogenation of sorbic acid and its derivatives can be defined by the position at which the hydrogen addition occurs. alcohols.[7] was K3[Co(CN)5]. The addition of hydrogen at positions 2. partly herbaceous and slightly acidic. it is sweeter and more fruity than cishex-3-en-1-ol and it is often used as a component of artificial strawberry. If in this reaction one of the isomers is formed preferentially the reaction is described as stereoselective hydrogenation. In methanol the selectivity to trans-hex-2-enoic acid was higher. With water as a solvent the ratio of transhex-2.372 Libor Červený and Eliška Leitmannová it can be used in imitations of mint and different fruit mixtures. In the presence of polyethyleneglycol (phase transfer compound) the selectivity decreased to 81 %. Due to this fact hydrogenation reactions in the presence of benzyltriethylammonium chloride take place in the organic phase.1 MPa). When benzyltriethylammoniumchloride was added to this system the proportion of trans-hex-3-enoate formed was increased to 75 %. For the hydrogenation of sorbic acid a series of different Rh complexes was tested [13] at room temperature with a hydrogen pressure of 0.Hexenoic Acids and Their Derivatives [Co(CN)5H]3- 373 + X H X Co(CN)5 3- X X Co(CN)5 3- Co(CN)5 3- H X H H X H Figure 1. On the other hand using [RhCl (PPh3)2 (Ph2PO2CCH=CMe2)] a mixture containing 52 % of hex-4-enoic acid and 48 % of hexanoic acid was obtained after total conversion of sorbic acid. In a twophase water-dichloromethane system methyl-trans-2-enoate and trans-hex-3-enoate were formed in a 65:35 ratio. in contrast when tetraalkylamonium compounds are present complexes such as [R4N]3 [Co(CN)5H] are formed and these are soluble in organic solvents. A similar result was obtained by Alper [12] for the hydrogenation of potassium sorbate using similar conditions with a different phase transfer compound (beta-cyclodextrine). 0. . In addition this complex was more active than Wilkison´s catalyst.3 Pa in basic solution. The differences in the behavior of the reactions are probably a result of the different media in which the reactions occur [11]. In the absence of a phase transfer compound the selectivity to trans-methyl-hex-2-enoate (hydrogenation of methylsorbate) was 90 %. ORGANOMETALLIC COMPLEXES BASED ON RHODIUM The investigations into the use of complexes based on cobalt were followed by the examination of different Rh complexes. Sorbic acid was not hydrogenated under the chosen reaction conditions (room temperature. Selectivity to trans-hex-2-enoate was slowly decreased using natrium sorbate in the hydrogenation.and trans-hex-3-enoate of 75% and 13 % respectively. Another step was to determine the effect of phase transfer compounds on the course of the reaction [10]. This author obtained yields for trans-hex-2. Hydrogenation[9] of dienes using [CoIII(CN)5H]3. Without phase transfer compounds the reaction takes place in the aqueous phase. Using Wilkinson´s catalyst [RhCl(PPh3)3] even at low conversion only saturated hexanoic acid was formed. 9 % of methyl-cis-hex-3-enoate. R X H2 Cr(CO3)Y R H CO Cr CO X H R H H 1 X CO Figure 2. Based on these results the reaction mechanism generally accepted to date was formulated (Figure 2). acetone).2-addition of hydrogen and the consecutive isomerisation was therefore eliminated. During the study of the influence of the arene substituents on the structure and activity of the catalyst it was found that electron accepting substituents accelerate the catalytic reaction while electron donating groups significantly decrease the activity of the catalyst [16]. ORGANOMETALLIC COMPLEXES BASED ON CHROMIUM The hydrogenation of methyl sorbate to methyl-cis-hex-3-enoate was enabled [15] using complexes of the types [Cr(CO)3]. The activity of the different complexes differs significantly depending on the ligand whereas selectivity was almost unaffected by the type of ligand. The obtained values of selectivity were from 91. The highest activity (at 150 °C) was obtained using the complex with 3carbomethoxyanisol as an arene ligand. Diene hydrogenation[15] using [(arene)Cr(CO)3] complexes S = solvent (THF. . 120°C).4 h-1 at 165 °C). Using temperatures higher than 50 °C trans-hex-2-enoic acid was subsequently hydrogenated to hexanoic acid after the total conversion of sorbic acid. Y = arene.8 to 98. [Cr(CO)6]. The initial step of the catalysis is the dissociation of the arene ligand from the Cr complex followed by the formation of the coordinately unsaturated species [Cr(CO)3]. As a model reaction for the study of this phenomenon the hydrogenation of methyl sorbate to methyl-cis-hex-3-enoate was used.1 MPa and a temperature of 30 – 40 °C with DMSO as the solvent trans-hex-2-enoic acid with a small amount of trans-hex-3-enoic acid was obtained. This demonstrates that the hydrogen was transferred directly to carbon atoms 2 and 5 of methylsorbate. [W(CO)3] and [(arene)Cr(CO)3]. The authors detailed the results obtained through the comparison of different arene ligands. In this work [15] it was found that the arene group is not necessary for this reaction as the complex [(cycloheptatriene)Cr(CO)3] showed a higher activity than the complexes [(aren)Cr(CO)3]. As stated above almost no influence on selectivity was observed and for almost all the catalysts with different substituents 100 % selectivity to desired methyl-cis-hex-3-enoate was obtained. a hydrogen pressure of 4.8 MPa and a catalyst : substrate ratio of 1 : 9. Reactions were carried out at temperatures of 150 . In cyclohexane solution the benzene complex showed the lowest activity (TOF = 2.165 °C. The reaction path including 1. The hydrogenations were performed in THF for 5 hours (6 MPa H2. At a hydrogen pressure of 0. X = CO2Me. When other solvents were used the catalyst was significantly less active and selective.374 Libor Červený and Eliška Leitmannová Another Rh catalyst used [14] was [H2RhIII(Ph2N3)2(PPh3)2]. To date the most active compound was [(naphtalen)Cr(CO)3] that stereoselectively catalyzed hydrogenation [19] of methylsorbate at a temperature of 30 °C and a hydrogen pressure of 0. of the arene complexes showed that a longer bond length between chromium and the carbon atoms of the arene ligand correlated with increased dissociation. A comparison [17]. .4-diene-1-ol. From these disadvantages the main is toxicity of chromium carbonyl compounds. The catalyst : substrate ratio was 1 : 20 and the desired cis-hex-3-en-1-ol was obtained with 96 % selectivity and TOF = 5 h-1.180 °C and 5 MPa using chromium hexacarbonyl as the catalyst. Using all the described heterogenized Cr catalysts very high leaching was observed and catalysts lost their activity after reuse. The direct 1. trans-hex-3-enoic and trans-hex-2enoic acids with trans-hex-2-enoic acid as the major component was obtained.Hexenoic Acids and Their Derivatives 375 It was demonstrated that the simple dissociation of the arene ligands from chromium resulted in higher activity of the catalyst. A temperature of 190 °C and a hydrogen pressure of 5 MPa were necessary for reactions using all the [(arene)Cr(CO)3] complexes. esters. In spite of their high selectivity.1 MPa. Heterogenization was accomplished by linking the Cr(CO)3 groups to the phenyl ring of polystyrene. a mixture of cis-. anthracene or phenanthrene. Unfortunately the attempt to reproduce the described heterogenization method followed by hydrogenation was not successful [23].3-trimethoxybenzene)Cr(CO)3] the plane [18] formed from C-atoms of the ring was significantly deformed and this complex was active even at a temperature of 80°C. In recent work a Cr complex with similarly high activity was prepared by Kündig [21]. Using some of these the Cr catalyst was successfully heterogenized [22] by mixing chromium hexacarbonyl with polystyrene. The cause [20] of such high activity is probably the solvatation of the naphtalene complex in THF. The catalyst could be reused with no loss of selectivity. ketones and carboxylic acids). The stereoselective hydrogenation of conjugated dienes using chromium catalysts is not limited to the hydrogenation of methylsorbate but was also used [17] for the synthesis of many other natural compounds. And finally the stereoselective hydrogenation of sorbic acid itself is not possible. forming [(THF)3Cr(CO)3]. In [(1. hydrogenations using chromium hexacarbonyl and [(aren)Cr(CO)3] complexes as catalysts have many disadvantages.1 MPa.4-hydrogenation of sorbic acid using Cr complexes as catalysts failed. than high catalyst : substrate ratios . The heterogeneous Cr catalyst had lower activity in comparison with [(aren)Cr(CO)3] complexes but had similar selectivity. The author prepared the η2-methylacrylate complex [(C6H6)Cr{CH2CH(CO2CH3)}] that catalyzed the hydrogenation of methylsorbate at room temperature and 0. Sorbic acid and its potassium salt were hydrogenated [25] at 160 . Furuhata [24] used 1.4-hydrogenation for the direct synthesis of cis-hex-3-en-1-ol from hexa-2. During these syntheses it was found that the reaction can be applied to molecules containing many different functional groups (non-conjugated double bonds. This phenomenon was more evident in Cr-carbonyl complexes of the polyaromatic compounds like naphtalene. The problem is also that the industrial use of homogeneous Cr catalysts is not described and the reactions with heterogenized catalysts were not reproducible.2. The main undesired product was saturated hexanoic acid.5 h-1. namely low activity.E. When the catalyst was used for different sorbic acid derivatives the selectivity was strongly dependent on the dienic system. In this newly formed complex the positions 2 and 5 in the molecule of . After the π –complex formation with sorbic acid the oxidative addition of one molecule of hydrogen takes place.376 Libor Červený and Eliška Leitmannová ORGANOMETALLIC COMPLEXES BASED ON RUTHENIUM Heinen [26] synthesized a water soluble complex of ruthenium [RuCl2{P(CH2)3OH}]2 that catalyzed the hydrogenation of sorbic acid to trans-hex-4-enoic acid with 82 % selectivity in a two-phase water-ethylacetate system. The increase in the selectivity for the desired product in the twophase system was probably due to the extraction of the primary (unsaturated) products of the reaction into the organic phase and the resulting shift of the equilibrium. The stereoselective hydrogenation of sorbic alcohol was not possible using this complex. This catalytic system had [27] some disadvantages. The addition of the dienic system where the diene is in the cis-conformation was proved by Mashima [29] based on the complexation reaction of (E. At 62 % conversion the reaction rate determined by TOF was 15.7-octatetraene with [Cp*RuCl]4. the hydrogenation of sorbic aldehyde produced a mixture of hexenals. which was formed with 22 % selectivity. The water soluble [Cp*RuCl(CO){P((CH2)3OH)3}] complex catalyzed the hydrogenation of sorbic acid at 80 °C and 5 MPa in a two-phase water-heptane system with 66 % selectivity to cis-hex-3-enoic acid.5. A highly active catalytic system (80 °C. The acetonitrile ligands dissociate stepwise from the catalyst and the molecule of sorbic acid is simultaneously added through its C=C double bonds. in this case the catalyst remained in the nitromethane phase in contrast with water as polar phase. Using a hydrogen pressure of 5 MPa the TOF of sorbic acid was 15 h-1 and that of ethyl sorbate was 18 h-1 at 60 °C.3. The Cp*Ru(diene) complexes described by Fagan [30] contain the diene in the cis-conformation. After the dissociation of the acetonitrile ligands and the addition of the diene a similar complex to the Cr systems was formed. Due to the absence of other ligands in the [Cp*Ru(MeCN)3]Tf complex it was deduced that the high selectivity probably results solely from the cationic RuCp* fragment. When the reaction was carried out in a one-phase system (water) the selectivity was only 62 % and the rest of the mixture was composed of hexanoic acid.E)-1. 5 MPa) producing cis-hex-3-enoic acid with 67 % selectivity was obtained. The alternative to Cr catalysts mentioned above (preparation of cis-hex-3-enoic acid) was also developed by Heinen [27]. The selectivity was strongly dependent on the conversion due to the isomeric activity of the system.E. selectivity of only up to 90 % and the impossibility of the use of nitrormethane as an industrial solvent as it is explosive at higher temperatures.8-diphenyl-1. A particularly suitable catalyst for this reaction appeared [27] to be the cationic [Cp*Ru(MeCN)3]+ complex (the counter ion was triflate (Tf)). A further development was the use of a two-phase system with nitromethane as a polar phase. When the reaction took place in a two-phase system with water as one of the phases strong leaching of the catalyst to the nonpolar phase was observed. Sorbic acid and its ethyl ester were hydrogenated in a two-phase nitromethane – heptane system to cis-hex-3-enoic acid with 75 % selectivity or to ethyl-cis-hex-3-enoate with with 84 % selectivity. As a result the following reaction mechanism was proposed [28] (figure 3). Sorbic alcohol was hydrogenated with 82 % selectivity (total conversion) to cis-hex-3-en-1-ol. = CF3SO3. nitromethane or sulfolane and is insoluble in nonpolar solvents such as ethers or alkanes. [Cp*Ru(η4-MeCH=CHCH=CHCO2H)]+X. Postulated mechanism[28] of sorbic acid hydrogenation to cis-hex-3-enoic acid (S = solvent). + Ru NCMe CF3SO3- MeCN MeCN + S Ru S S Tf +sorbic acid .5}4]. This was the reason for the synthesis [28]. cis-3-hexenová .(X.cis-hex-3-enoic acid +S +S + S Ru S COOH Tf Ru S + Tf - COOH +2S H Ru H + Tf COOH + H2 -S Figure 3. In the final step of the catalytic cycle the cis-hex-3-enoic acid dissociates from the Ru center and the solvated Cp*Ru complex is free for the addition of a new molecule of sorbic acid. It can be used as a catalyst in liquid two-phase systems including nitromethane-dibuthylether.[31]. ethyleneglycol-MTBE or sulfolane-MTBE where the complex remains in the polar phase.kys.or [B{C6H3(CF3)2-3. After the reaction the catalyst can be simply separated by decantation.[32] of the model Cp*Ru complexes i.2S + kyselina sorbová -2S .e. Complexes were obtained as orange powder or crystals with yields of 72 % and 41 % respectively. that are were efficient complexes for the hydrogenation of sorbic acid to cis-hex-3-enoic acid and of sorbic alcohol to cis-hex-3-en-1-ol (leaf alcohol) under mild conditions using a twophase liquid system.(BARF)). The results obtained showed that the “naked” [Cp*Ru]+ . At 60 °C the solvents in the nitromethane-dibutylether and sulfolane-MTBE systems become soluble but at room temperature they are insoluble.Hexenoic Acids and Their Derivatives 377 sorbic acid are angled directly towards the hydride ligands and the transfer of hydrogen to these positions is very probable. The first of the complexes is soluble in polar solvents such as alcohols. One face of the active center is blocked by the Cp* ligand and the other is available for reaction with the substrate molecules. The undesired hemiacetals are formed due to the migration of the double bond on the chain forming the unstable monounsaturated aldehydes and by the reaction of these compounds with the alcohols present in the reaction. In this system the activity of the catalyst was significantly higher in comparison with the system used previously (TOF up to 1100 h-1) but the selectivity to cis-hex-3-enoic acid was lower. The undesired side products (other isomers of hexenoic acids) are formed by isomerisation on the active center. in the case of sorbic alcohol the undesired side products are hemiacetals or acetals respectively. In subsequent work [34] the most selective catalyst was used in a two-phase system with MTBE and dibutylether as the non-polar product phase and the ionic liquid Bmim PF6 (1-nbutyl-3-methylimidazolium hexafluorophosphate) as the polar catalyst phase. It was found that the hydrogen was placed solely in positions 2 and 5 in sorbic acid molecule. This interaction is nonbonding and no effect on selectivity was expected (this was confirmed in the sorbic acid hydrogenation.can be used [35] for the hydrogenation of different dienes to their cis-unsaturated forms. Catalysts of the type [Cp*Ru (diene)]+X.378 Libor Červený and Eliška Leitmannová particle is more active than the Ru catalysts used previously. Methyl and butyl esters of sorbic acid were also hydrogenated [38] using the optimal catalyst and a higher selectivity to the desired cis-unsaturated product was observed due to the decrease in electron density. The catalysts obtained by these modifications can catalyze the hydrogenation of the chosen dienes with high selectivity and activity. To prove the reaction mechanism shown in Figure 3. This type of immobilization did not affect the selectivity and the catalyst could be reused with no loss of selectivity and minimal loss of activity. The author used sorbic acid and sorbic alcohol and also cyclooctadiene. On the both of the methylene groups of cis-hex-3-enoic acid exactly one proton was present (assigned by 1H-NMR). Two types of heterogenization were tested – at first the immobilisation using hydrogen binding [39] through the oxygen of the triflate ion. The mechanism of the hydrogenation of different hexadiene compounds (acid or alcohol) was studied. No saturated hexanol was detected in the mixture. . In the sorbic alcohol hydrogenation this reaction did not occur [37]. The catalysts of the type [Cp*Ru (diene)]+X. a spectroscopic study of the hydrogenation was carried [33] out. in the sorbic alcohol hydrogenation the selectivity was marginally lower due to the synergic effect). The second type of immobilization tested was using ionic exchange [40] of Na cations of different anionic clays with the cation of the active complex. In the sorbic acid hydrogenation it was found that the monounsaturated acid formed could also interact with the Ru active particle (π-electrons of C=C double bond and C=O carbonyl group) and hydrogenation does not stop at the desired cis-hex-3-enoic acid and the final product could be hexanoic acid. Modifications of the counterion Xwere also tested as was the modification of the other ligand of the pentamethylcyclopentadiene complex by exchange with indenyl or fluorenyl.can not only be used in two-phase or homogeneous systems as the immobilization of these catalysts was also successfully performed. In the case of sorbic acid the undesired side products are the other hexenoic acids. It was confirmed [36] that the mechanism forming the desired product proceeded in accordance with the scheme shown above (Figure 3) but the reaction of the desired product with the Ru center to form of undesired side products was different for the both of the compounds. For the hydrogenation of sorbic aldehyde this type of catalyst is not applicable due to its deactivation by the aldehyde itself. . Possible solvatation of the catalyst[38] (S =solvent). zinc powder (2.to 18 e-).3 mmol)(or another hydrogenated diene).1 mmol). The prepared catalyst is soluble in polar solvents and slightly soluble in ethers. Water is a catalytic poison and causes catalyst deactivation.023 g of [Cp*RuCl2]n (0. + Tf Ru S COOH Ru S + Tf - S S Figure 4. The second step could be total solvatation (Figure 4) of the complex resulting in the formation of the clusters (Figure 5). + Tf + Ru S S Ru S S Tf - Tf - S S Ru S S Ru Tf - + + Figure 5. In the polar solvents fast degradation of the complex was observed (the solution quickly became brown).3 mmol) and silver triflate (0.08 mmol)was obtained as a powder.Hexenoic Acids and Their Derivatives 379 PREPARATION AND PROPERTIES OF [CP*RU (DIENE)]+CF3SO3 The optimal preparation of the catalyst is described in the patent [35]. One of the possible cluster. 0.5 hour at ambient conditions. The use of polar solvents results in the formation of strong (binding) interactions with the complex.08 mmol) was dissolved in diethylether (5 ml) with an excess of sorbic acid (1. An orange solution was formed and after solvent evaporation and purification [Cp*Ru(sorbic acid)]CF3SO3 (0. Interactions with the Ru center could be formed by the free electron pairs [38] and saturation of the complex may occur in the first step (16 e. When alcohols were used as solvents it was found that longer carbon chains in the alcohols resulted in lower solubility of the complex and slower catalyst degradation. The mixture was stirred for 2. Air humidity causes slow catalyst deactivation and it is possible to store the catalyst in air for 24 hours with no loss of catalytic properties. The coordinately unsaturated particles are the components of the catalytic cycle in the reactions catalyzed by transition metals. This author studied the . This property distinguishes it from the unsubstituted cyclopentadienyl ligand and is a result of the higher electron density of the Cp*-ligand. Summary of the catalysts used for the hydrogenation of C6-dienic compounds Catalyst K3[Co(CN)5] K3[Co(CN)5] K3[Co(CN)5] K3[Co(CN)5] Substrate Potassium sorbate Methylsorbate Methylsorbate Methylsorbate Product Sel. [6].380 Libor Červený and Eliška Leitmannová Table 1. [32] [38] and [38] [RhCl(PPh3)2(Ph2PO2CCH= Sorbic acid CMe2)] [H2RhIII(Ph2N3)2(PPh3)2] Sorbic acid [(aren)Cr(CO)3] Methylsorbate [(aren)Cr(CO)3] [(aren)Cr(CO)3] [RuCl2{P(CH2)3OH}]2 [RuCl2{P(CH2)3OH}]2 [Cp*RuCl(CO){P((CH2)3O H)3}] [Cp*Ru(MeCN)3]Tf [Cp*Ru(MeCN)3]Tf [Cp*Ru(MeCN)3]Tf [Cp*Ru(sorbic acid)]Tf Sorbic alcohol Sorbic acid Sorbic acid Sorbic acid Sorbic acid Sorbic acid Sorbic alcohol Ethylsorbate Sorbic acid 52 trans-Hex-2-enoic acid 90 Methyl-cis-hex-3-enoate 92-99 cis-Hex-3-en-1-ol trans-Hex-2-enoic acid trans-Hex-4-enoic acid cis-Hex-3-enoic acid cis-Hex-3-enoic acid cis-Hex-3-enoic acid cis-Hex-3-en-1-ol Ethyl-cis-hex-3-enoate cis-Hex-3-enoic acid cis-Hex-3-en-1-ol 96 40 82 62 66 67 82 84 96 94 [Cp*Ru(sorbic alcohol)]Tf Sorbic alcohol [Cp*Ru(sorbic aldehyde)]Tf Sorbic aldehyde No selectivity [Cp*Ru(methylsorbate)]Tf Methylsorbate Methyl-cis-hex-3-enoate 96 [Cp*Ru(butylsorbate)]Tf [Cp*Ru(sorbic acid)]Tf [Cp*Ru(sorbic acid)]Tf Butylsorbate Sorbic acid Sorbic acid Butyl-cis-hex-3-enoate cis-Hex-3-enoic acid cis-Hex-3-enoic acid cis-Hex-3-en-1-ol 99 97 97 85 [Cp*Ru(sorbic alcohol)]Tf Sorbic alcohol Two-phase heteroegeneous Two-phase and [38] heterogeneous Heterogeneous – [39] hydrogen binding Heterogeneous – [40] ionic exchange Heterogeneous [39] [RUCP*] FRAGMENT The pentamethylcyclopentadienyl ligand (Cp*-ligand) is of particular importance in organoruthenium chemistry due to its ability to stabilise unsaturated ruthenium complexes. [31]. [32] [28].[27]. The first work dealing with catalytic hydrogenation of sorbic acid using RuCp* complexes were performed by Heinen [26].[8] [10] [11] [12] [13] [14] [15] [19] [24] [25] [26] [26] [26] [27] [27] [27] [28].95 enoate Methyl-trans-hex-290 enoate Methyl-trans-hex-265 enoate Methyl-trans-hex-375 enoate trans-Hex-4-enoic acid Arrangement Homogeneous Homogeneous Two-phase Two-phase (+ phase transfer compound) Homogeneous Homogeneous Homogeneous Homogeneous Homogeneous Two-phase Homogeneous Two-phase Two-phase Two-phase Two-phase Two-phase Two-phase Lit.82 . [31]. (%) Potassium trans-hex-2. [Cp*Ru]+ has a high affinity for 6π-electron systems as demonstrated by the formation of [Cp*Ru(aren)]+ cations after the reaction with cyclic olefins and the elimination of water. 2 RuCl3. Its reaction with silver triflate in the presence of the well coordinating solvent acetonitrile gave the [Cp*Ru(NCMe)3]Tf complex that was the necessary precursor for the [Cp*Ru(arene)]+ compounds. Ligands including CO. forming 18e. Detailed information is given in two reviews from Chaudret [46] and Koelle [47].complexes such as [Cp*RuL2Cl]. The catalytically active particle was probably the solvent stabilized lewis acid [RuCp*]+ fragment.3H2O + Cp*H [Cp*RuCl2]2 + 2 HCl + 3 H2O equation 1 This complex can be reduced [43] byLi[Et3BH] to [Cp*RuCl]4 and in accordance with Koelle[44] using methanol in the presence of base to [Cp*Ru(μ-OMe)]2 (figure 6). phosphines or dienes decomposed the tetramers. The methanolate bridges can be substituted by thiols [48] with retention of the structure.Ru(IV)-complex [Cp*Ru(μ3-all)Cl2]. This particle could be coordinated to by many different ligands. Reduction[43] of [Cp*RuCl2]2. This complex offers the possibility of many different reactions that are shown in the following scheme (figure 8).Hexenoic Acids and Their Derivatives 381 [Cp*Ru(CO)(PR3)Cl] and [Cp*Ru(CO)(PR3)]Tf (R = alkyl) complexes but they had low catalytic activity. Through this the [Cp*Ru(C6H6)]Tf complex with two equivalents of hydrogen was . Typical reactions [45] of the tetrameric [Cp*RuCl]4 complex are shown in Figure 7. The [Cp*Ru(MeCN)3]Tf complex had significantly higher activity and contained relatively simply substitutable acetonitrile ligands. Treating [Cp*Ru(μ-OMe)]2 with strong acid after methanol elimination gave the noncharacterized solvent stabilized particle [Cp*Ru]+. Cp* 2 [Cp*RuCl2]2 + 4 Li[Et3BH] Cp* Ru Ru Cl Cp* Cl Cl Cl Ru Cp* Ru + 4 LiCl + BEt3 Me O [Cp*RuCl2]2 +3 MeOH + 2 K2CO3 Ru O Me Ru Figure 6. The usual entry to RuCp* chemistry begins from the dark brown dimeric (polymeric) Ru(III) complex [Cp*RuCl2]2 that was examined independently in the groups of Bercaw [41] and Suzuki[42] (equation 1). Donor ligands such as dppm or bipy can be added [44] to the complex. Oxidative addition of allylchloride gave the 18e. Trans-2 isomers can even be obtained using heterogenous catalysts so the main goal was the preparation of the cis-3 isomers. PMe3 L Ru Cl L + dien 1/4 [Cp*RuCl]4 + C6Me6 +NH4PF6 . C-O and C-Cl bonds could be also realized whereas C6-compounds such as cyclohexene are aromatized. using organometallic complexes with different central atoms to monounsaturated compounds. The properties of these complexes are described in detail in the chapters. . MeCN +2L L = CO. + Ru NCMe + AgTf. the activation of C-C. But these are surpassed by complexes with the simple structure [Cp*Ru(diene)]+ where the diene is the hydrogenated compound (sorbic acid or sorbic alcohol or other derivative). Typical reactions[44] of [Cp*RuCl]4. Besides the activation of C-H bonds described. especially sorbic alcohol.382 Libor Červený and Eliška Leitmannová obtained [49] after the reaction of [Cp*Ru(μ-OMe)]2 with triflouromethanesulphonic acid and cyclohexene at 80 °C in methylenechoride.AgCl Cl Cl Ru Cl CF3SO3- MeCN MeCN Ru Cl Ru Figure 7. The use of different complexes based on Rh. Cr and Ru initially showed that the most selective complexes were those based on Cr. The selectivities in these cases are up to 98 %. CONCLUSION This text gave brief overview of the selective hydrogenation of sorbic acid and its derivatives. Mabrouk A. Červený L.Am.: Coll. 101 (1986). 153 (1964). Klusoň P.Lett. Kwiatek J. B 63.: Perfume and Flavour Chemicals. N.:React..Proc. Fialová E.. De Vries B. 41. 54. Růžička V. Červený L.Ned. Published by author. L. Kukula P... Koninkl. 59. K. Cowan J. 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C20 (1992). 268 (1995). 1313 (1998)..Am. 423.: J. Koelle U. . China 3 Institute of Biomass Chemistry and Technology.56-1. from 0. Fourier transform infrared and solid-state cross-polarization/magic angle spinning 13C NMR spectroscopies also provided evidence of catalyzed homogeneous succinoylation reaction. indicating that these three catalysts were effective catalysts for cellulose succinoylation in ionic liquids.54 under the experimental conditions catalyzed with iodine. 4-dimethylaminopyridine. Guangzhou. and 4-dimethylaminopyridine (DMAP) in a solvent system containing 1-butyl-3methylimidazolium chloride ionic liquid ([C4mim]Cl) and dimethylsulfoxide (DMSO).94-2. A. Li1.C.F. Poehler ©2011 Nova Science Publishers. W. Beijing.cn .92-2. and C-3 positions in cellulose occurred. Lan1 and R. W. Chapter 12 HOMOGENEOUS CATALYZED SUCCINOYLATION OF CELLULOSE IN IONIC LIQUIDS C. 0. Zhang1. Beijing Forestry University. Nbromosuccinimide. ionic liquids * Corresponding author. Inc. Sun1.In: Homogeneous Catalysts: Types.2. China 2 Institute of of New Energy and New Material. The possible mechanism of homogeneous succinoylation catalyzed with these catalysts and the actual role of these catalysts were also investigated. Reactions and Applications ISBN: 978-1-61122-894-6 Editors: Andrew C.34 with DMAP. Guangzhou. The effects of the mass ratio of catalyst/SA.3 State Key Laboratory of Pulp and Paper Engineering. China 1 ABSTRACT Homogeneous modification of sugarcane bagasse cellulose with succinic anhydride (SA) was catalyzed with three different catalysts including iodine. and 0. Keywords: cellulose. The results indicated that the reaction of hydroxyl groups at C-6. The results showed that the DS of cellulosic derivatives increased to 0. N-bromosuccinimide (NBS). South China University of Technology.Y. succinoylation. C-2. and reaction temperature on the degree of substitute (DS) of cellulose were investigated. Liu*1. catalyst.24 without any catalysts. reaction time.31 with NBS.
[email protected]. iodine. South China Agricultural University.edu. galactose. biofuels. and biocomposites in native. Acylation of cellulose with linear chain acylation reagents such as anhydride or chloride is the most common method to produce cellulosic bioproducts. US Department of Energy has targeted to achieve 10% of basic chemical building blocks arising from lignocellulose-derived renewables by 2020. to create biofuels. cellulose is a homopolymer composed of D-glucopyranose units linked by β (1→4) glycosidic bonds [7]. Chemically. Liu. Li et al. homogeneous cellulose functionalization has been one focus of cellulose research for a long time [14. and cellulose. Zhang. waxes. Functionalization of cellulose using ionic liquids (ILs). Cellulose acetylation with acetic anhydride or acetyl chloride has . hemicelluloses. lignin. there is a growing urgency to develop novel bio-based products and other innovative technologies that can unhook widespread dependence on fossil fuel around all over the world [1]. formate [20]. are the second most abundant renewable materials after cellulose in plant cell walls [8].Y. bioenergy. Hemicelluloses. W. A. and mannose. The integrated utilization of lignocellulosic biomass is becoming the significant issue and development tendency. as reaction media has attracted much attention after cellulose was reported to be soluble in a variety of ILs with strong hydrogen bond acceptors as anions.12]. and alkylphosphate [20. The promising applications of cellulose include biofibers. the lignocellulosic biomass is firstly fractionated to three main components. but also contributes to reduce environmental concerns regarding the disposal of the residues [10]. Due to three hydroxyl groups available within one anhydroglucose units (AGU) in cellulose. even as one of the most important policy-oriented research activities in developed countries. and a further increase to 50% by 2050 [1]. The European Union has also developed a vision in which one-fourth of the EU’s transportation fuels will be derived from biofuels by 2030 [5].24-26]. Chemical modifications of cellulose can introduce functional groups into the macromolecules in heterogeneous phase or homogeneous phase to improve the overall utilization of cellulosic polymers. a great variety of chemical modifications of cellulose are possible [13]. that is. It has been estimated that about 50% of biomass in the world is lignocellulose. In the promising utilization pattern. Utilization of biomass. one of the most promising green solvents. INTRODUCTION Recently. degraded. of which polysaccharides including cellulose and hemicelluloses account for over two-thirds [6]. biopolymers. acetate [21-23]. especially inedible lignocellulosic biomass. It is about 35-43% of the dry lignocellulosic materials. These political timetables result in critical challenges in biomass utilization. The utilization of these biomacromolecules not only adds value to the biomass raw materials. an amorphous complex polymer usually composed of xylose. The remainder is mostly lignin plus lesser amounts minerals. Modification of cellulose represents one of the most versatile transformations as it provides access to a variety of biobased materials with valuable properties. which account for about 25-35% of the dry lignocellulosic materials. Because more uniform and stable products can be obtained in homogeneous phase than heterogeneous phase. biochemicals. much of which is in a crystalline structure. or modified status [11. and other compounds [9]. 1. and then the isolated components are independently utilized to produce different products according to their own properties. biocomposites and a host of other bioproducts has attracted considerable attention around all over the world [2-4]. glucose.388 C.F.P. arabinose. such as chloride [16-19].15]. Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids 389 been extensively studied because of the wide application of cellulose acetate. NBS.. . 4-dimethylaminopyridine (DMAP) and N-bromosuccinimide (NBS) were explored in a reaction medium containing ionic liquid 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) based on their good catalytic effects on the esterification of alcohols.2. 2. 5 mL of DMSO was added to reduce viscosity and achieve a suitable mixing. Materials Sugarcane bagasse (SCB) was obtained from Guangzhou. natural absorbents for the removal of heavy metal ions in wastewater treatment. and used as received. and perpropionylation with propionic anhydride [31] were also investigated in ILs. Hangzhou.1. and thermoplastic materials [32.. and DMAP Dried SCB cellulose was added to [C4mim]Cl in three-necked flask. All of other chemicals used were of analytical grade and purchased from Sigma-Aldrich. medicine for drug delivery systems. EXPERIMENTAL 2. the reaction results in a pendant carboxylic moiety attached to the cellulose molecules via a covalent ester bond. The possible mechanisms of catalyzed succinoylation were discussed. China. 2. It was dried in sunlight and then cut into small pieces. and only the cellulose derivatives with relatively low DS were obtained [34. Guangzhou. Ionic liquid [C4mim]Cl was obtained from the Chemer Chemical Co. The mixture of cellulose/[C4mim]Cl was stirred up to 10 h at 80 oC under N2 atmosphere to guarantee the complete dissolution of cellulose.8-4. The cellulosic derivatives were then characterized by Fourier transform infrared (FT-IR). providing a site upon which further reactive chemistry is possible. acylation with lauroyl chloride [29]. The cut SCB was ground and screened to prepare 20-40 mesh size particles (450-900 μm). Homogeneous Succinoylation of Cellulose Catalyzed with I2.35].0 followed by alkaline extraction with 10% potassium hydroxide. modification of cellulose with cyclic anhydride such as succinic anhydride are widely used to produce water absorbents for soil in agriculture. and solid-state CP/MAS 13C nuclear magnetic resonance (NMR) spectroscopies. However. China. Carbanilation with phenyl isocyanate [29.27-30]. To the resulting cellulose solution. Cellulose was isolated after delignification of ground SCB with sodium chlorite at pH 3. Then catalyzed succinoylation reaction was carried out according to the following procedures. China. three different catalysts including iodine (I2). On the other hand.31]. To increase cellulose succinoylation efficiency. and the results showed that cellulose acetates with high degree of substitution (DS) were easily prepared [18.33]. Ltd. our previous studies showed that succinoylation was much more difficult than acetylation. Moreover. Succinoylation Catalyzed with NBS NBS and SA was dissolved in 5 mL DMSO. 100 g/mol is the net increase in the mass of an AGU for each succinoyl substituted. and then added to the cellulose solution in [C4mim]Cl/DMSO system at the corresponding reaction conditions shown in Table 2. A.Y. The mixture was stirred under N2 atmosphere for the desired time. and byproducts. 2 mL of saturated solution of sodium thiosulfate was added to the modified cellulose solution with agitation. The mixture was vigorously shaken for 2 min to guarantee complete transformation of iodine to iodide. m is the weight of sample analyzed. After cooling.390 C. 2.3.2. and then dried in a vacuum at 50 oC for 16 h. Zhang. The residues were filtrated out. and then dried in a vacuum at 50 oC for 16 h. 5-6 drops of phenolphthalein indicator were added.37]. washed thoroughly with isopropanol to eliminate ILs.2. After the required time. and then added to the cellulose solution in [C4mim]Cl/DMSO system at the corresponding reaction conditions shown in Table 1. The mixture was stirred under N2 atmosphere for the desired time. washed thoroughly with isopropanol to eliminate ILs. After the required time. 2.F.2. .P. Succinoylation Catalyzed with DMAP DMAP and SA was dissolved in 5 mL DMSO. unreacted anhydride. unreacted anhydride. The mixture was stirred under N2 atmosphere for the desired time. the resulted mixture was slowly poured into 150 mL of isopropanol with agitation. unreacted anhydride. 2. Li et al. and cNaOH is the molarity of standard NaOH solution. After the required time. W. washed thoroughly with isopropanol to eliminate ILs. and byproducts. The residues were filtrated out. Liu. Then the resulted mixture was slowly poured into 150 mL of isopropanol with agitation. 2.3. VNaOH is the volume of standard NaOH solution consumed in the titration. The DS was calculated by using the following equation: where 162 g/mol is the molar mass of an AGU.01 M standard NaOH solution until a permanent pale pink color was seen. and byproducts. and then dried in a vacuum at 50 oC for 16 h. A known weight of the sample was dissolved in 10 mL of DMSO by stirring at 75 oC for 30 min. This solution was titrated against 0. the resulted mixture was slowly poured into 150 mL of isopropanol with agitation. Determination of Degree of Substitution The DS of cellulosic derivatives was determined by direct titration method [36. and then added to the cellulose solution in [C4mim]Cl/DMSO system at the corresponding reaction conditions shown in Table 3. The residues were filtrated out.2.1 Succinoylation Catalyzed with I2 I2 and SA was dissolved in 5 mL DMSO. degree of polymerization. respectively.Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids 391 2. RESULTS AND DISCUSSION 3. and 206800 g·mol−1. 1277. Part 1.034 s. Molecular weight (Mw) of cellulose was then calculated from P by multiplied by 162. Part 1. Acquisition time was 0. cupriethylenediamine (CED) method (BS 6306.65[η]. and the proton 90o pulse time 4. 1982). The spectrometer operated at 100 MHz. the viscous cellulose solution obtained was diluted by DMSO to achieve suitable and clear mixture. Succinoylation Catalyzed with Iodine Delignification of SCB with sodium chlorite followed by alkaline extraction yielded 49.90=1. where P is an indeterminate average DP [38]. In the . The solid-state CP/MAS 13C NMR spectra were obtained on a Bruker DRX-400 spectrometer with 5 mm MAS BBO probe employing both Cross Polarization and Magic Angle Spinning and each experiment was recorded at ambient temperature. Figure 1. and molecular weight of the isolated cellulose were determined to be 378 mL·g−1. Usually. 3. the delay time 2 s.4. Iodine has been reported recently as an effective catalyst for acetylation of alcohols and polysaccharides without solvents [39. Each spectrum was obtained with an accumulation of 5000 scans. After cellulose was dissolved in [C4mim]Cl. P0. The intrinsic viscosity.40].85 μs. The FT-IR spectra of the cellulose and succinylated cellulosic derivatives were recorded on an FT-IR spectrophotometer (Nicolet 510) from finely ground samples (1%) in KBr pellets in the range 4000-400 cm-1. SA reacts with cellulose O-H groups to form the monoester as shown in Figure 1. Solid acylation reagent SA and catalysts previously dissolved in DMSO were added to the diluted solution to achieve homogeneous succinoylation reaction. the Mw of an AGU.6% cellulose (based on the dry weight of SCB).1. Scheme for succinoylation of SCB cellulose with succinic anhydride. Thirty-two scans were taken for each sample with a resolution of 2 cm-1 in the transmission mode. The viscosity average DP (degree of polymerization) of cellulose was estimated from their intrinsic viscosity [η] in CED hydroxide solution. In the present study. succinoylation of the obtained cellulose with different catalysts in [C4mim]Cl/DMSO system was investigated to improve cellulose derivatizing efficiency. Characterization of the Native and Succinylated Cellulose Viscosity of the cellulose was measured by British Standard Methods for determination of limiting viscosity number of cellulose in dilute solutions. A.0 4:1 2. DS of succinylated cellulose with succinic anhydride in [C4mim]Cl/DMSO using iodine as a catalyst. including the mass ratio of I2/SA from 2% to 15%.0 4:1 2.24 without any catalysts to the range of 0. reaction temperature from 85 to 110 oC.0 4:1 I2/SA (%) Temperature (oC) Duration (min) 2 100 60 5 100 60 8 100 60 10 100 60 15 100 60 10 100 30 10 100 45 10 100 90 10 100 120 10 85 60 10 90 60 10 95 60 10 105 60 10 110 60 Succinylated cellulose Sample No. Table 1 shows the effects of the parameters.0 4:1 2.34 10 0.0 4:1 2.0 4:1 2. 8%.92 13 1. present study.0 4:1 2.0 4:1 2. respectively. DS decreased from 1.54 a Molar ratio of SA to anhydroglucose unit (SA/AGU) in cellulose was 4:1.28 4 1.34 with a further increment of reaction duration from 90 min to 120 min.41 and 1. W. a plausible explanation is that iodine might first be ionized into . In present study. 100.97 8 1.56-1.41 and 1. Raising reaction temperature from 85 o C to 90.41 5 1. This decrement was probably due to the further reaction of succinic acid attached to cellulose with hydroxyl group in the near surroundings to form diesters in the presence of iodine. suggesting that iodine could be an effective catalyst for cellulose succinoylation in ionic liquids. DS 1 0. 1. the maximum DS observed was only about half of the theoretical maximum vale 3.39.24.84 3 1.F. Table 1. data not shown). 95.64 11 0.0 4:1 2. Succinoylation conditions Cellulose (%) Molar ratioa 2.0 4:1 2. Zhang.52 9 1.56 to 0.0 4:1 2. and 90 min led to an increment in DS from 0. 1.41.1.54 in the presence of iodine catalyst under the conditions given. This increment indicated that the efficiency of succinoylation in the presence of iodine increased. and reaction duration from 30 to 120 min. Liu. compared with that obtained under the same conditions without any catalysts (DS=0.46 and 1. As shown in Table 1.0 4:1 2.0 4:1 2.54. on DS of the succinylated cellulose.52 respectively.78. The possible mechanism of iodine-catalyzed succinoylation and the actual role of iodine are not clear. However.56 2 0. 10% and 15% (based on SA) resulted in an improvement of the DS of cellulose derivatives from 0.46 14 1.0 4:1 2.56. 0. However.97.84. 60.P.Y.72 7 0.72 to 0. 1. we investigated the possibility of cellulose succinoylation catalyzed with iodine in [C4mim]Cl/DMSO to increase cellulose modification efficiency. DS of cellulose derivative obtained with the addition of 2% iodine (based on SA) increased to 0. The improvement of iodine dosage from 2% to 5%.392 C.28. Li et al.52 to 1.92. 105 and 110 oC resulted in an increase in DS from 0. However. Prolonging reaction duration from 30 min to 45. The similar decreased acylation of cellulose modified with lauroyl chloride was also reported in ILs [29]. respectively.78 12 0.64 to 0. 1.39 6 0. the DS of cellulose derivatives increased from 0. 23.e.27 to 1. The reason of this decrease in DS was probably due to the formation of diester in the presence of catalyst NBS by crosslinking of the produced succinic acid attached to cellulose. 1. Possible mechanism of the iodine-catalyzed succinoylation of cellulose.99 in 90 min. In present study. The addition of 1% NBS (based on SA) resulted in the DS enhancement from 0. indicating the significant improvement of succinoylation in the presence of NBS. 1.31. Succinoylation Catalyzed with NBS NBS is an inexpensive and commercially available reagent that is traditionally used as an oxidizing agent or brominating agent in radical reactions and various electrophilic additions [41]. Higher reaction temperature was also . reaction temperature at 100 oC and NBS/SA mass ratio at 2%. This decrement was also found in iodinecatalyzed succinylation. I+ in turn activates the carbonyl groups of SA to form as the acylation reagent for further reaction. further improvement of NBS/SA mass ratio from 5% to 10% and 20% led to a reduction of DS from 2.55 and 1.2. DS of cellulose derivatives reached 0. 3. with other free hydroxyl groups in the surroundings. cellulose succinoylation was discussed in [C4mim]Cl/DMSO system using 4:1 molar ratio of SA/AGU in cellulose. Figure 2. However.31 to 1. and 2.84 and 2..84 within 60 min. It is also a mild and efficient catalyst for acetylation of alcohols and phenols under mild reaction conditions [42]. a mass ratio of NBS/SA between 0 and 20%. as shown in Figure 2. These results indicated that NBS could significantly improve the reaction efficiency of SA and cellulose in [C4mim]Cl/DMSO system.27.24 to 1.31 with 45 min. An increase of NBS/SA mass ratio from 1% to 2% and 5% resulted in noticeable improvement of DS from 1. i. the efficiency of cellulose succinoylation in [C4mim]Cl/DMSO system was significantly enhanced with catalysis of NBS compared with that without any catalysts. Clearly. Table 2 shows the DS of cellulose derivatives obtained with NBS catalyst. monoester.Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids 393 I+ and I− in ILs.92 in 75 min.03 in 120 min when keeping the molar ratio of SA/AGU at 4:1. respectively. 1. reaction temperature 90-120oC and reaction duration 30-240 min. 1. respectively.92 within 30 min. A. 1.92 45 21 1.0 4:1 2. Table 2.F.0 4:1 2.99 120 24 2. .73 60 26 1. Possible mechanism of the NBS-catalyzed succinoylation of cellulose.0 4:1 2.84 60 17 2.74 60 28 1. DS 60 15 1.0 4:1 2.25.0 4:1 2. 110 and 120 oC resulted in an enhancement in DS of cellulose derivatives from 1.0 4:1 2.84.0 4:1 2. DS of succinylated cellulose with succinic anhydride in [C4mim]Cl/DMSO using NBS as a catalyst.31 75 22 1. Improving reaction temperature from 90 to 95. favorable to NBS-catalyzed succinoylation.394 C. respectively.0 4:1 2. Succinoylation conditions Cellulose (%) Molar ratioa 2.23 30 20 0.03 240 25 1.98 60 29 2.27 60 16 1. Li et al.0 4:1 2.0 4:1 2. 1.92 90 23 1.98 and 2. Figure 3.P.0 4:1 NBS/SA (%) Temperature (oC) 1 100 2 100 5 100 10 100 20 100 2 100 2 100 2 100 2 100 2 100 2 100 2 90 2 95 2 110 2 120 Succinylated cellulose Duration (min) Sample No. Liu.0 4:1 2. 100.55 60 19 1.31 60 18 1. Zhang. W.67 to 1.0 4:1 2.74.0 4:1 2.Y.67 60 27 1.0 4:1 2.25 a Molar ratio of SA to anhydroglucose unit (SA/AGU) in cellulose was 4:1. 55 1.0 4:1 5 110 2. In present study. DMAP was found to be approximately 104 times more active when used as acylation catalyst [44].19 2. DMAP is a derivative of pyridine with the chemical formula (CH3)2NC5H4N.0 4:1 5 80 2. In comparison to pyridine. . which produce succinoylated cellulose upon elimination of NBS. Succinoylation Catalyzed with DMAP Pyridine has been found to be effective in the modification of wood with various long chain anhydrides. It is a very useful nucleophilic catalyst for a variety of reactions such as esterifications of alcohols with anhydrides.24 without any catalysts to the range of 0.0 4:1 5 100 2.78 1.0 4:1 8 80 2.Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids 395 The DS of cellulose derivatives increased from 0.19 1. The possible mechanism of NBS-catalyzed succinoylation is shown in Figure 3.0 4:1 5 80 2.38 a Molar ratio of SA to anhydroglucose unit (SA/AGU) in cellulose was 4:1.31 in the presence of NBS catalyst under the conditions given.52 1.0 4:1 5 80 2.3.0 4:1 3 100 2. but also catalyzes the reaction via nucleophilic mediated catalysis [43].0 4:1 15 80 2. pharmaceuticals and polymers as an acylation catalyst.0 4:1 5 60 2. 3.28 1.92-2. and reaction duration from 30 to 120 min on DS of cellulose derivatives succinylated in [C4mim]Cl/DMSO system.93 1. Table 3.0 4:1 1 80 2.0 4:1 2 80 2.0 4:1 5 70 2.75 2. because it serves not only to swell the wood structure.0 4:1 5 80 2.0 4:1 5 90 2.94 1. It has been used in the synthesis of agrochemicals. DS 60 60 60 60 60 60 60 60 60 60 60 30 45 90 120 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 0. Succinoylation conditions Cellulose (%) Molar ratioa DMAP/SA (%) Temperature (oC) 2.52 1. which in turn activates the carbonyl groups of SA to produce the highly reactive acylating agent. NBS might act as a source for Br+. DS of succinylated cellulose with succinic anhydride in [C4mim]Cl/DMSO using DMAP as a catalyst.88 1.34 1.69 1. reaction temperature from 60 to 110 o C. thereby permiting effective ingress of reagent. This acylating agent reacts with hydroxyl groups of cellulose.0 4:1 5 80 Succinylated cellulose Duration (min) Sample No. we investigated the possibility of succinoylation catalyzed with DMAP in ILs. Table 3 shows the effects of the mass ratio of DMAP/SA from 1% to 15%.49 1. 88 to 1. Figure 4 illustrated the possible role of DMAP in catalyzed succinoylation. 1. reaction temperature at 80 oC and molar ratio of SA/AGU at 4:1.34. The absorption band at 1164 cm-1 corresponds to C-O antisymmetric bridge stretching [45]. Holding DMAP/SA mass ratio at 5%. which could react with cellulose hydroxyl groups and produce cellulose ester.78 in 60 min.88 with the enhancement of DMAP/SA mass ratio from 1% to 2%. Possible mechanism of the DMAP-catalyzed succinoylation of cellulose. Figure 4. 1. In spectrum 1. 2929.78. The peak at 1372 cm-1 is due to the O-H bending. Further improvement of DMAP dosage from 8% to 15% led to slight decrease in DS from 1. A strong peak at 1049 cm-1 arises from C-O-C pyranose ring skeletal vibration [46]. The possible mechanism of DMAP-catalyzed succinoylation of cellulose is similar to DMAP-catalyzed acetylation.19. The band at 1633 cm-1 relates to the bending mode of the absorbed water. FT-IR Spectra Figure 5 illustrates the FT-IR spectra of native cellulose and succinylated cellulose with or without catalysts.38 with further elongation of reaction duration from 60 min to 90 and 120 min. 90 and 100 oC resulted in an improvement of DS from 1. and 1049 cm-1 are associated with native cellulose. respectively.Y.94 to 1.P. 1633. The DS was improved from 0.78 to 1.69. 1. and 1. indicating the enhanced succinoylation efficiency in [C4mim]Cl/DMSO in the presence of DMAP.396 C.94-2.52 in 45 min.F. 80. 5%. DS of cellulose derivative increased to 0. DS of cellulose derivatives reached 1.93 with further improvement of reaction temperature from 100 to 110 oC. and 1. respectively. 1164.19. and 2.34 to 1. However. As shown in Table 3. The DS of cellulose derivatives increased to the range of 0.94 with addition of 1% DMAP (based on SA). The strong adsorption at 3434 cm-1 is attributed to the stretching of hydroxyl groups and that one at 2929 cm-1 corresponds to the CH stretching. Li et al. 1.75.4. the absorbances at 3434. A. The increase of reaction temperature from 60 to 70. W.34 in the presence of DMAP catalyst under the conditions given.52. 3. The nucleophilic attack of DMAP on a carbonyl group of succinic anhydride leads to intermediate.78. DS was slightly reduced from 2. DS decreased from 1. respectively. 3%. and 8%. Zhang.28 within 30 min.49 and 1. 1372. 2.55 to 1. . Liu. The intensities of the two peaks at 1728 cm-1 for carbonyl groups and at 1574 cm-1 for carboxylic anions significantly increased. The former band at 1728 cm-1 is an overlapping of the absorptions by carbonyl groups in carboxyl acids and esters [47].5. 3. and the spectra of unmodified cellulose (spectrum a). 100 95 90 85 80 75 %T 70 65 60 55 50 45 40 3500 3434 1728 1164 2929 1574 1412 3 1372 1633 2 1 1049 3000 2500 2000 Wavenumbers (cm-1) 1500 1000 Figure 5. FT-IR spectra of unmodified cellulose (spectrum 1). succinylated cellulose without any catalysts (spectrum b) and with NBS as a catalyst (spectrum c. It indicated that iodine. the catalyzed succinoylation reaction of cellulose was also studied by solid-state CP/MAS 13C-NMR spectroscopy. spectrum 2 of succinylated cellulose without any catalyst provides evidence of succinoylation by the occurrence of the absorbance at 1728 and 1574 cm-1. Similar results were also found in the FT-IR spectra of succinylated cellulose samples catalyzed with NBS and DMAP (spectra not shown). In addition. The latter band at 1574 cm-1 is originated from antisymmetric stretching of carboxylic anions [33]. sample 13) are shown in Figure 6. NBS and DMAP are efficient catalysts of cellulose succinoylation in [C4mim]Cl/DMSO. More importantly. succinylated cellulose without any catalyst (spectrum 2) and with iodine as a catalyst (spectrum 3. spectrum 3 of succinylated cellulose with iodine catalyst provides the more evidences of catalyzed succinoylation. indicating the formation of monoester.Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids 397 Compared with spectrum 1. sample 7). . suggesting that the catalyzed esterification reaction does occur. As expected. the intensity of the absorption band at 1164 cm-1 for C-O antisymmetric stretching clearly increased after succinoylation. the absence of peaks at 1850 and 1780 cm-1 in spectra 2 and 3 for succinylated cellulose confirmed that the products are free of the unreacted SA. Solid-State CP/MAS 13C-NMR In the present study. sample 15). the intensities of the signals at 171 ppm for carboxylic group and 26. These results suggested that iodine. Liu. indicating that NBS could significantly improve the modification efficiency of cellulose with SA in [C4mim]Cl/DMSO system. the signals at 85. the intensity of the signal for C-6 decreased after succinoylation. suggesting the complete disruption of cellulose crystalline structure during the dissolution and functionalization. A.0 ppm for carboxylic group and 26. Li et al. and that at 67.4 ppm for methylene group significantly increased compared with that in spectrum b without any catalysts.4 ppm for methylene group also provided evidence of succinoylation.Y. C-2. Clearly. PPM Figure 6. As shown in Figure 6. which indicated that succinoylation reaction occurs in homogeneous phase. succinylated cellulose without any catalysts (spectrum b) and with NBS as a catalyst (spectrum c.398 C.F. In spectrum c of cellulose derivative succinylated with NBS catalyst. . Zhang. As shown in Figure 6. the presence of the signals at 171. Evidently. W. all noticeable signals in spectrum a of unmodified cellulose are distributed in the region between 50 and 110 ppm for the carbon atoms of the carbohydrate moiety.1 ppm for C-6 of crystalline cellulose disappeared in spectra b and c of succinylated cellulose. The three free hydroxyl groups at C-6.8 ppm for C-2 and C-3 also decreased. NBS. which indicated the succinoylation reaction at C-6. and DMAP are effective succinoylation catalysts of cellulose in [C4mim]Cl/DMSO. and C-3 positions does occur. and C-3 position in AGU are the main reactive sites in cellulose.P. Solid state CP/MAS 13C-NMR spectra of unmodified cellulose (spectrum a).2 ppm for C-4 of crystalline cellulose and 61. which indicated the reaction shown in Figure 1 does occur. C-2. The similar observations were also found in the spectra of cellulose derivatives catalyzed with iodine and DMAP (spectra not shown). Selective production of xylose and xylo-oligosaccharides from bamboo biomass by sulfonated allophane solid acid catalyst. Biomass & Bioenergy. Applied Microbiology and Biotechnology. LT. ME. M. WS. [2] [3] [4] [5] [6] . Brady. NBS. The results showed that these three catalysts could effectively improve the cellulose succinoylation. RX. Nimlos. 2001. JR. Y. Ichikuni. and 30710103906). 10. Cui. JB. the Guangdong Natural Science Foundation (No. YHP. TD. J. R. Wu. DK. ACKNOWLEDGMENTS The authors are grateful for the financial support of this research from the National Natural Science Foundation of China (Nos. Hatakeyama. 17-34. Adney. 97. Biomass recalcitrance: Engineering plants and enzymes for biofuels production.56-1. RT. 56. SY. ME.31 with NBS catalyst. Under the given conditions the DS of cellulose derivatives increased from 0. 525-532. N. and DMAP. Shinozuka. Fractionating lignocellulose by formic acid: Characterization of major components. Lynd. LR. 214-223.Homogeneous Catalyzed Succinoylation of Cellulose in Ionic Liquids 399 CONCLUSION The homogeneous modification of sugarcane bagasse cellulose with succinic anhydride in solvent system containing ionic liquid 1-butyl-3-methylimizolium chloride and dimethylsulfoxide was catalyzed with three different catalysts including iodine. Shimazu. 2009ZZ0024). 8451064101000409). MR. S. and National Basic Research Program of China (No. SY. 19-26.94-2. ZM. 30972325. Zhang. Chinese Universities Scientific Fund (No. Y. Misra. 0. Ding. Laser. 2002. Nielsen. Zaldivar. 30871994. The possible mechanisms of homogeneous catalyzed succinoylation were also proposed. Liu. 2009. Ogaki. Himmel. He. 1176-1177. Journal of Polymers and the Environment. Qi. 804-807. Biotechnology and Bioengineering. Johnson. Drzal. Specialized Research Fund for the Doctoral Program of Higher Education (No. 34. T.54 with iodine catalyst. AK.24 to 0. 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Comparative study of cellulose isolated by totally chlorine-free method from wood and cereal straw. 803811. F. RC. Balaji. Zhang. [44] Hill. 391-411. N. JX. XF. R. Sun. [46] Sun.P. Studies on copolymers of 2-(nphthalimido)ethyl methacrylate with methyl methacrylate. Zhang. 2001. 50. 97. ZC. 36. Xu. 2000. RC. Separation and characterization of cellulose from wheat straw. XF. S. 2000. . Ozmen. 269-272. Potential catalysts for the acetylation of wood.F. J.Y. CAS. NS. 54. A. FY. Sun. RC. Geng. [47] Jayakumar. European Polymer Journal. 39. Li et al. Separation Science and Technology. Liu.ndimethylformamide/lithium chloride systems. 322-335. W. [43] Sun. 2005. Powai. Pd. inherently possesses important attributes like. The specialty of Pd as a metal lies in its ability to efficiently construct numerous types of C−X (X = C. Inc. edited by Kenneth M. Reactions and Applications ISBN: 978-1-61122-894-6 Editor: Andrew C. India ABSTRACT The knowledge of the efficient formation of C−X (X = C and N) bonds asymmetrically or otherwise is vital to contemporary organic synthesis. O and S) bonds under ambient conditions. N. Poehler © 2011 Nova Science Publishers. .iitb. the strong palladium−N-heterocyclic carbene (Pd−NHC) interaction help stabilizes many catalytically important active species at low * * A version of this chapter was also published in Palladium: Compounds. Production and Applications . thereby generating an enormous interest in its palladium complexes in recent years. It was submitted for appropriate modifications in an effort to encourage wider dissemination of research.ac. which together constitute two important steps in numerous catalysis cycles. the N-heterocyclic carbenes (NHC) have added a new chapter in the design. Mumbai 400 076. Brady.In: Homogeneous Catalysts: Types. Nova Science Publishers. the air and moisture stability and the functional group tolerance.and regio selectivities that facilitate the synthesis of intricate target molecules otherwise not conveniently accessible by traditional methods.in. Of late. being a late transition metal. In this context notable is the contribution of Pd towards the development of the area. The strong σ-donating nature of the N-heterocyclic carbene ligand in the catalyst allows oxidative insertions of challenging substrates while the ligand topological steric demands promote the fast reductive elimination reactions. Additionally. which often are the key ingredients of a successful catalyst. discovery and development of Pd catalysts. A key strength of Pd mediated synthesis thus lies in its chemo. Chapter 13 PALLADIUM COMPLEXES OF N-HETEROCYCLIC CARBENES IN HOMOGENEOUS CATALYSIS AND BIOMEDICAL APPLICATIONS * Chandrakanta Dash and Prasenjit Ghosh* Department of Chemistry Indian Institute of Technology Bombay. Fax: +91-22-2572-3480. Furthermore. Email: pghosh@chem. ease of preparation. N. Though numerous catalysis with palladium have long been reported under the “Ligand Assisted Catalysis” (LAC) conditions. the palladium N-heterocyclic carbene complexes exhibit promising potential in various biomedical applications like in the anticancer studies. and thereby prevent catalyst leaching.[7.[3. being extremely air and moisture sensitive. air and moisture stability.404 Chandrakanta Dash and Prasenjit Ghosh ligand to Pd ratios and also at high temperatures thereby broadening its scope of catalytic applicability. that avoid not only the large use of expensive ligands but also eliminate the excess ligand removal step at the end of the catalysis.[6] the use of well-defined catalysts is advantageous in many respects like in maintaining a strict control of the optimal 1:1 palladium/ligand ratio.Notable is the versatility of palladium that makes it interesting among metals for the expedient construction of numerous C−X bonds (X = C. N.[1] In this context the transition metals occupy a special place particularly for their role in both the stochiometric and catalytic bond formations[2]. the palladium catalysts are often functional group tolerant thus allowing it to function in synthetically delicate conditions. which is in sharp contrast to the other frequently encountered alkali and transition metal based reagents like that of Li. A prominent hallmark of the palladium complexes in general and its N-heterocyclic carbene ones in particular is their ability to efficiently execute the catalytic formation of a variety of C−X (X = C and N) bonds under amenable conditions. O and S) in varied challenging environments and thereby thriving as a metal of choice under catalytically demanding situations. The N-heterocyclic carbenes (NHCs) are fast emerging as an important ancillary ligand of choice that provide an appropriate platform for designing effective transition metal catalysts for a variety of important transformations in recent years. require stringent handling measures. the rising status of the N-heterocyclic carbene catalysts can be attributed to their superior performance.and O-donor ligands ubiquitous in numerous homogeneous catalysts. Apart from the C−X (X = C and N) bond forming reactions.4] The metal’s popularity stems from providing convenient access to key steps of various preparative protocols for the compounds of industrial and academic interests. Mg and Zn etc. They are often seen as convenient alternatives to the phosphines. that mostly participate in stoichiometric bond formations and also. an important attribute of a successful catalyst. because of their tighter binding. INTRODUCTION Smart and efficient formation of strategic bonds represents a perennial challenge in the world of organic synthesis and has largely propelled the development of various types of C−X (X = C. non-toxicity and the high efficiency at low catalyst loading.8] The N-heterocyclic carbenes are good σ-donors[9] that favor strong binding to metals in general. Even extending further beyond chemical catalysis. N. owing to reduced ligand dissociation. . Tsuji-Trost reaction and the polymerization reactions etc. O and S) bond forming reactions into powerful synthetic tools in the ever expanding arsenal of organic methodologies. Furthermore. the Pd complexes of N-heterocyclic carbenes perform various other reactions like the oxidation reactions. Thus. the N-heterocyclic carbenes stabilize many catalytically relevant intermediates via a combination of electronic and steric effects.[5] The other important attributes of palladium lie in its robustness and high air and moisture stabilities that facilitate indefinite storage and easy handling of its compounds. Additionally. h. b In this context the well-characterized examples of the Pd(0). the electronic effects of palladium. Though much rare compared to the Pd(II) counterparts. and subsequently employed in various catalysis like the. Sonogashira. The monograph presents recent developments in the emerging utility of palladium N-heterocyclic carbene complexes in the homogeneous catalysis and in their newly evolving biomedical applications.j (Scheme 1). The palladium(II) N-heterocyclic carbene complexes are primarily synthesized by any of the following three routes.g Palladium(II) N-Heterocyclic Carbene Complexes Among the three oxidation states. the Pd(II)/Pd(IV) shuttle too have been reported in some cases. obtained from the reaction of an azolium salt and Ag2O.f. g telomerization of 1. the Pd(0) Nheterocyclic carbene complexes have been synthesized primarily by employing two successful strategies.c. Negishi.e. there have been conscious efforts in the past toward directly accessing these catalytic cycles through well-characterized intermediates. with Pd(II) precursors. while the second method involved either the reduction of a Pd(II) species in presence of a Nheterocyclic carbene ligand or the direct reduction of a palladium(II) N-heterocyclic carbene complex itself (Scheme 2) to yield the desired palladium(0) N-heterocyclic carbene complex.Palladium Complexes of N-Heterocyclic Carbenes … 405 Remarkable is the ever growing portfolio of catalytic transformations partaken by palladium N-heterocyclic carbene complexes that span from the C−C bond forming reactions namely. The flexibility in conveniently shuttling between different oxidation states allows palladium to participate in numerous catalytic cycles involving oxidation and reduction sequences in the form of oxidative addition and reductive elimination steps.e. a. Palladium(0) N-Heterocyclic Carbene Complexes Recognizing the importance of Pd(0)/Pd(II) shuttle in many catalytic cycles. (i) by transmetallation of the silver N-heterocyclic carbene complexes.h Heck–Mizoroki. provide optimal reactivity for catalysis as the first row ones are noted for their high reactivity while the third row ones are comparatively inert and hence the both of these are not so effective as catalysts compared to the second row metals on many occasions. Heck–Mizoroki. Kumada-Tamao-Corriu. Hiyama.f. In this regard several Pd(0) complexes (1−21) of Nheterocyclic carbenes[10] have been synthesized (Figure 1).i Sonogashira. Stille. some even structurally characterized.3-dienesd and aryl aminationb.b.g reactions etc. First one.[11] (ii) by the . the simplest of the two approaches. Additionally. being a second row transition element. Suzuki−Miyaura.c. e. Though Pd(0)/Pd(II) shuttle is more commonly encountered. the Suzuki–Miyaura. Pd(II) and Pd(IV) complexes of N-heterocyclic carbenes assume relevance. involved the direct reaction of a Pd(0) species with a N-heterocyclic carbene ligandd.i. b. α-ketone arylation. hydroarylation and carbonylation reactions to the C−N bond formations like the aryl amination and hydroamination reactions. the Pd(II) is by far the most commonly observed one with the contemporary literature inundated with numerous palladium(II) N-heterocyclic carbene complexes mainly because of their new-found success in homogeneous catalysis. 406 Chandrakanta Dash and Prasenjit Ghosh direct reaction of the azolium salts with Pd(II) precursors in presence of a base[12] and (iii) lastly. (NHC)2Pd (NHC)2Pd Pd(0) (PR3)2Pd NHC Pd(0) (alkene) (COD)Pd(alkene) (NHC)Pd(alkene) Scheme 1. (NHC)2Pd(alkene) . by the oxidative addition of an activated C−H bond in an azolium salt on the metal center of a Pd(0) precursor (Scheme 3).[13] Figure 1. Pd[OCMe2CH2(1C{NCHCHNiPr}][benzo(h)quinoline]. Palladium(IV) N-Heterocyclic Carbene Complexes The Pd(IV) species are extremely rare compared to the Pd(0) and Pd(II) species and consequently.Palladium Complexes of N-Heterocyclic Carbenes … 407 reduction [Pd(allyl)Cl]2 NHC (NHC)2Pd reduction (NHC)Pd(allyl)Cl L (L = PR3 or NHC) Scheme 2. the Pd(II)/Pd(IV) shuttle is less invoked than the Pd(0)/Pd(II) shuttle in various palladium mediated catalytic cycles. The structurally characterized example of a Pd(IV) Nheterocyclic carbene complex (22) (Figure 2) remained elusive until recently with the appearance of a report of a Pd(IV) N-heterocyclic carbene complex synthesized judiciously by the oxidative addition of two chloride ligands to a Pd(II) complex.[14] . (NHC)Pd(L) Scheme 3. using PhICl2 (Scheme 4). Though the phosphines have traditionally enjoyed a wide spread utility in palladium mediated catalysis. C−C Bond Forming Reactions Palladium mediated catalytic C−C bond formations under amenable conditions have revolutionized the world of organic synthesis in the last few decades and have emerged as versatile synthetic tools for the smart and expedient preparations of numerous target molecules today. even surpassing the phosphines on many occasions. .408 Chandrakanta Dash and Prasenjit Ghosh Figure 2. of late. Scheme 4. The monograph next discusses the various catalysis performed by palladium Nheterocyclic carbene complexes. the N-heterocyclic carbenes are seeing unprecedented popularity in this area. The catalysis studies were performed either under “Ligand Assisted Catalysis” (LAC) conditions. numerous attempts have been made in recent years in exploring their potential in the Suzuki−Miyaura cross-coupling reaction. The difficulty of achieving the Suzuki–Miyaura coupling of aryl chlorides largely stems from the stronger C−Cl bond than the other C–X (X = Br. The aryl chlorides.[16] Initial phases of the developments of the catalyst design and discovery for the coupling reaction mainly rode on the back of phosphine based systems till the advent of N-heterocyclic carbenes in this area. In keeping with the phenomenal successes of N-heterocyclic carbenes in catalysis. convenience in product isolation and minimal toxicity issues. is among the highly used methods available today for the construction of the biaryl frameworks ubiquitous in numerous bioactive molecules. notable is an unsymmetrically substituted imidazolium bromide salt 31 (Figure 3) which in presence of a palladium(0) precursor. Br (80) and I (65)]. The N-heterocyclic carbenes have largely propelled the development of the Suzuki– Miyaura C–C cross-coupling reaction in the last two decades to an extent that the reaction is now finding routine use in both industry and academia alike.Palladium Complexes of N-Heterocyclic Carbenes … 409 Suzuki–Miyaura Cross-Coupling Reaction The Suzuki–Miyaura reaction.[17] thereby making the coupling of aryl chlorides a topic of contemporary interest. The popularity of the reaction primarily arises from its tolerance towards a broad range of functional groups and from the several other advantages normally associated with the use of organoboron reagents like its ease of accessibility. a formidable challenge. diverse and inexpensive. though obvious. lies in utilizing the cheap and readily available aryl chlorides for the cross-coupling reaction.3 x 107 for the coupling of phenyl iodide with phenyl boronic acid. Thus. I) bonds [bond dissociation energy (kcal/mol) for Ph–X: Cl (95). involving the in situ generation of an active catalyst from the ligand and a metal precursor. from both the academic and industrial perspectives. vinyl.[18] nearly two decades after the initial discovery of the Suzuki–Miyaura reaction with the aryl bromide substrates. which are more challenging by virtue of being less reactive in contrast to the aryl iodide and bromide ones that readily undergo the cross-coupling reaction. Among the “Ligand Assisted Catalysis” (LAC) reported with the N-heterocyclic carbenes. Pd2(dba)3 (dba = dibenzylideneacetone). involving the palladium catalyzed C−C cross-coupling of organoboron derivatives with aryl-. exhibited extremely high turnover number (TON) of 3. Particularly interesting is the Suzuki–Miyaura cross-coupling of aryl chloride substrates.[19] Specific emphasis lay on designing suitable catalysts exhibiting high turnover numbers (TONs) or the ones with the ability to perform more challenging and also synthetically coveted aryl chloride coupling. are in great demand for use as substrates for the crosscoupling reaction. or using well-defined precatalysts.or alkyl halides. It is worth mentioning that the N-heterocyclic carbenes were originally introduced by Hermann as late as in 1998[15] in the Suzuki–Miyaura reaction long after the initial discovery of the cross-coupling reaction by Suzuki and Miyaura in 1979.[16] and thereby underscoring the underlying challenges associated with the coupling of aryl chlorides. In this regard it is worth mentioning that significant efforts have been made toward developing catalysts for the coupling of aryl chlorides with the first breakthrough appearing only in 1998 using custombuilt sterically demanding phosphine systems. pharmaceuticals and natural products (Scheme 5).[20] . being more abundant. 4-i-Pr-C6H4 (25). a 1.3-dialkylperhydrobenzimidazolinium chloride salts 23−27[22] and its related unsaturated counterparts.[21] Significant breakthroughs have been achieved in the coupling of the more difficult aryl chloride substrates using N-heterocyclic carbenes. The catalysts exhibiting ultra-high turnover numbers enjoy an additional advantage of avoiding any tedious catalyst separation step often required at the end of the catalytic cycle and thereby adding to the overall cost effectivity of the process. It is worth mentioning that catalysts with ultra-high turnover numbers (TONs) are primarily important from the point of utilizing only little amount of the expensive palladium metal as well as the N-heterocyclic carbene ligands for the catalysis. 4-Et-C6H4 (24). (Figure 3) carried out the cross-coupling of aryl chlorides at a relatively low temperature 80 °C in good to excellent yields.410 Chandrakanta Dash and Prasenjit Ghosh R X + R' M Pd-NHC complex R R' + M X R' M = organoboranes (Suzuki) organostannanes (Stille) organomagnesium (Kumada) organozinc (Negishi) organosilicon (Hiyama) amines (Buchwald-Hartwig) Sceme 5. 4-Ph-C6H4 (26). Another ferrocenyl phosphine functionalized imidazolium iodide salt 33 (Figure 3) exhibited a remarkably high turnover number (TON) of up to 20. H (29). F (30) 31 c-hex Cl N c-hex Fe PPh2 N NI t-Bu N c-hex c-hex 32 33 Figure 3.000 and a turnover frequency (TOF) of up to 10.000 h-1 for the cross-coupling of aryl bromides. Another sterically demanding phenanthryl derived N-heterocyclic carbene precursor 32[24] (Figure 3) . 4-OEt-C6H4 (27) R R Ad N N Cl Ad i-Pr i-Pr O O N Br N Br R = OMe (28). R N N Cl R R = 4-Me-C6H4 (23). Specifically. benzimidazolium chloride salts 28−30[23]. Palladium Complexes of N-Heterocyclic Carbenes … 411 performed the cross-coupling of aryl chlorides under ambient conditions i. In particular.05 mol %. (ii) bis-N-heterocyclic carbene complexes (B).f. The precatalysts. (iv) the mixed N-heterocyclic carbene and phosphine complexes (D) (Figure 4). Stabilization and Initiation) themed complexes (C) and lastly. both at room temperature and at 50 °C. the (NHC)Pd(allyl)Cl types 34−39[26] have been thoroughly studied by carrying out the variation of substituents on the allyl moiety like in 40−42[27] as well as on the N-heterocyclic carbene ligand like in 47−52[28] (Figure 5). (i) the mono-N-heterocyclic carbene complexes (A). the air and moisture stable precatalysts 34−38b showed high activity towards the cross-coupling of activated and unactivated aryl chloride and bromide substrates at 60-80 °C in presence of NaOtBu as a base. Specifically. Among the mono-N-heterocyclic carbene Pd(II) precatalysts. 40−42. efforts were directed toward designing Pd(0) and Pd(II) initiators of N-heterocyclic carbene ligands for the cross-coupling reaction. Notable are several palladium(0) complexes of N-heterocyclic carbenes having both saturated and unsaturated imidazole frameworks of type 9−16 (Figure 1) that have been successfully employed in the Suzuki−Miyaura cross-coupling reaction of aryl chlorides in good to excellent yields at 3 mol % of the catalyst loading. Significant reactivity difference could be seen among the precatalysts 47−49 in the coupling reaction performed at room temperature. The use of well-defined transition metal based initiators is advantageous particularly with regard to avoiding a large excess of expensive N-heterocyclic carbene ligands often seen under “Ligand Assisted Catalysis” (LAC) conditions. b. (iii) the PEPPSI (Pyridine Enhanced Precatalyst Preparation. e In sharp contrast to only a handful of examples known of Pd(0) precatalysts for the crosscoupling reaction. the approach calls for greater efforts with synthesis and characterization of well-defined discrete catalyst complexes.6-disubstituted aryl chlorides at a much lower catalyst loading of 0. The numerous palladium(II) N-heterocyclic carbene precatalysts that exist can be primarily classified into four types. . possessing different alkyl and aryl substituents on the allyl moiety. However. In this regard it is worth mentioning that Buchwald introduced the use of sterically demanding phosphine ligands for the cross-coupling of aryl chlorides.e. the precatalyst 42 performed the coupling of a wide range of aryl bromide. On the contrary. the precatalyst 39a was found to be only moderately active in the Suzuki−Miyaura coupling of aryl halides. Another precatalyst 50b carried out the coupling of aryl chlorides with 1-naphthalene-boronic acid at a low catalyst loading of 0. triflate and the chloride substrates with boronic acids at room temperature at an extremely low catalyst loading of 0.2 mol% in a short reaction time of 2 hours at 60 °C.[25] Parallel to the “Ligand Assisted Catalysis” (LAC) studies. the Pd(II) counterparts have been extensively studied..03 mol % under ambient conditions in good to excellent yields.h Another bis-oxazoline derived Nheterocyclic carbene palladium(0) complex 17 carried out the coupling of sterically demanding 2. exhibited high cross-coupling activity under ambient conditions at room temperature. c A slight variant of the Suzuki−Miyaura reaction employing aryldiazonium tetrafluoroborate salts as substrates instead of the ubiquitous aryl halides was reported using a palladium(0) N-heterocyclic carbene complex 21 at 50 °C. A similar type of naphthyl based (NHC)Pd(allyl)Cl precatalysts 47−49c performed better than the precatalysts 37 and 38 at 80 °C. PF6 and Cl). mesityl (44) R = 2.6-i-Pr2C6H3 (37). R' = Me (49). asymmetric Diels-Alder reaction etc. R = Me. R' = H (42) N i-Pr Cl i-Pr R N N R R N N R Pd Pd Cl Pd Cl X R' R N Pd Cl N R R' O N OX Pd Cl R R = R' = i-Pr (47). The ionic complex 53 showed high activity in carrying out the cross-coupling at low catalyst loadings of 0. hydrogen transfer reaction. . mesityl (46) R = Me. i-Pr R N N R R N N R N i-Pr Pd Cl Pd Cl R R' R = t-Bu (34). 54−58. Ph (52) 53 N O Cy2N O i-Pr N i-Pr N i-Pr Cl NCy2 N Mes N Pd N Mes i-Pr BF4 Pd Figure 5. Attempts toward designing mixed cyclopentadienyl and N-heterocyclic carbene systems of palladium. Another variation includes a series of N-chelated Nheterocyclic carbene palladium complexes 60−62.[31] and [(NHC)PdCl]+X. 2.(X = BF4. R = 2.[32] have been found to be good for the coupling of aryl chloride. hydroamination. R = R' = Me (48). X = (CH2)8 (50) R = H (51).[30] Several ionic complexes of the types [(NHC)Pd(allyl)]+BF4-. 53.5 mol %. R = 2.6-i-Pr2C6H3 (43). 2-(Ph)C6H4 (39) mesityl (36) R = Ph. 43−46[29] proved to be of limited success though these precatalysts performed the Suzuki−Miyaura cross-coupling of a wide range of substrates including the chlorides in room temperature. mesityl (38).05−0. R = H.6-i-Pr2C6H3 (35). In this regard it is noteworthy that cyclopentadienyl ligands have played a significant role in olefin polymerization. bromide and iodide substrates (Figure 6).412 Chandrakanta Dash and Prasenjit Ghosh Figure 4. R' = Me (41). asymmetric allylic alkylations.[33] 64−66[34] and 69[35] (Figures 6 and 7).6-i-Pr2C6H3 (45). R' = H (40). hydration of terminal alkynes to aldehydes. C−H activation. The benzthiazoline derived precatalysts 74−75[45] having a rare cis-geometry for unbridged non-chelated (NHC)2PdX2 type complexes showed turnover numbers (TONs) of up to 3. X = BF4 (57). notable are the 60. R' = n-C7H15. of which 70 efficiently catalyzed the Suzuki−Miyaura cross-coupling at low catalyst loading under mild reaction conditions (Figure 7). Of special mention is the 60 complex that exhibited high turnover number (TON) of up to 11.600 for the cross coupling of o-bromobenzaldehyde with phenylboronic acid at 85 °C in 12 hours of the reaction time. X = BF4 (54).Palladium Complexes of N-Heterocyclic Carbenes … X N Br Pd Br N N Cl O N N R' O N N Pd Cl N N N N N Pd Cl Cl Ph N Ph N N O Fe N Pd Cl Ph 413 N N N Pd Cl N R = Me.300 for the coupling of pbromobenzaldehyde with phenylboronic acid.[37] 68[38] and 70[39] complexes. Of these. R = Me. R' = n-Bu. The precatalyst 63[40] of the type (NHC)Pd(OAc)2 exhibited the cross-coupling of aryl chlorides and activated alkyl chlorides with aryl boronic acids. Specifically. Notable is a non-chelated trans-(NHC)2PdX2 type complex 71[41] that exhibited ultra high turnover number (TON) of 1. . 59 60 61 62 Me i-Pr N N Pd (OAc)2 N i-Pr i-Pr N Cl Me Me Pd S N N O O Pd N N N O Me O Me Pd Cl Cl N N N i-Pr 63 64 65 66 Figure 6. 62 and 69 precatalysts that carried out the Suzuki−Miyaura cross-coupling at low catalyst loadings. X = BF4 (55). 81. Similar type of non-chelated trans-(NHC)2PdX2 type complexes 72−73[42]. the non-chelated (NHC)2PdX2 (X = halide) and the chelated-(NHC)2PdX2 (X = halide) type complexes (Figures 8−9). a The other reported variations of precatalysts include mononuclear trans-[PdBr2(NHC)(imidazole)] (59)[36] and dinuclear [(NHC)Pd(μ-X)X]2 (X = halide) type 67.002 mol% exhibiting turnover numbers (TONs) of up to 13. R = Me. X = Cl (58). R = H.750 for the Suzuki−Miyaura cross-coupling of an activated p-bromoacetophenone substituent with phenylboronic acid. the precatalysts 90−91 performed the coupling reaction of 4-bromotoluene and phenylboronic acid at low catalyst loadings of 0. X = PF6 (56).09. R = Me.[43] 90−91[44] have been designed for the Suzuki−Miyaura cross-coupling of aryl halides with aryl boronic acids. R' = n-Bu. R' = n-C7H15. R' = mesityl. The bis-N-heterocyclic carbene palladium precatalysts primarily fall into two categories namely.700 at 85 °C in 24 hours. 76−77. The chelated cis-(NHC)2PdX2 type of complexes 83−86[48] and 89[49] displayed the cross-coupling of aryl bromides with phenylboronic acid.000 for the coupling of aryl bromides with phenylboronic acid.[51] 82[52] and 87−88[53] were found to be active for the cross-coupling of aryl and benzyl halides. trans to the metal bound strongly σ-donating N-heterocyclic carbene ligand (Figure 10). the precatalysts. However. showed ultra high turnover numbers (TONs) of up to 99. which would thus dissociate and give away to the incoming substrate.3-triazole derived abnormal N-heterocyclic carbene trans(NHC)2PdX2 type precatalyst 92[46] exhibited the cross-coupling of aryl bromides with aryl boronic acids. the observed activities were not too high. Stabilization and Initiation) themed precatalysts. unusual trans-dispositions were observed in the case of the 76 and 77 complexes. Particularly. Though chelated bis-(NHC)2PdX2 complexes often exhibit cisgeometries.000 for the coupling of aryl bromides with aryl boronic acids in neat water under aerobic conditions. which were originally designed with the intention of having a loosely bound “throwaway” ligand namely. The precatalysts 87−88 performed the cross-coupling of aryl boronic acids with aryl and arylmethyl bromides in water.2.[54] the N/O-functionalized N-heterocyclic carbene sidearm substituents 98−112[55] alongwith differently substituted pyridine variants 94−114e. an acyclic chelated diaminocarbene complex of type bis-(NHC)2PdCl2 93[47] has been reported for the cross-coupling of aryl bromide and chloride substrates with aryl boronic acids at 1 mol% of catalyst loading. displaying turnover numbers (TON) of up to 26. The strong trans effect of the N-heterocyclic carbene ligand was anticipated to weaken the binding of the diagonally opposite “throwaway” pyridine ligand. Several variations of PEPPSI themed precatalysts bearing nonfunctionalized 94−97. e. the o-xylyl-linked alkoxy benzimidazole precatalysts 83−86 exhibited moderate to high activities. Adding to the structural diversity. a 1. CH(Ph)2 (68) 69 Figure 7. The precatalysts 94−97 showed high activity in the Suzuki−Miyaura cross-coupling of aryl bromide and chloride substrates with the various boron derivatives like aryl boronic acids and alkyl-9-BBN (9-BBN . a pyridine moiety. The third category involves PEPPSI (Pyridine Enhanced Precatalyst Preparation. Other chelated bis-N-heterocyclic carbene precatalysts 78−80. Variation on the imidazole ring too has been attempted in the form of benzimidazole N-heterocyclic carbene PEPPSI precatalysts 113−114. have been synthesized. Quite interestingly.[50] Quite importantly. in which the two N-heterocyclic carbenes were linked by extended crown-ether linkages.414 Chandrakanta Dash and Prasenjit Ghosh OMe N N Pd N N OMe N N n-Bu n-Bu Pd N N N N 2 2Cl i-Pr N i-Pr N i-Pr i-Pr Pd Cl Cl Cl i-Pr N i-Pr 70 Cl Pd i-Pr N i-Pr N N R R Br Pd Pd Br R N Br R N N N n-Bu n-Bu Br R = i-Pr (67). 124−125. The precatalysts 143−146a have been used for the coupling of bulky aryl boronic acids with the aryl bromide and chloride substrates. Significantly enough.35 mol %.Palladium Complexes of N-Heterocyclic Carbenes … 415 = 9-borabicyclo[3. It is interesting to note that the ionic type [(NHC)PdX(PR3)2]+Xcomplexes 134−135 are more active than the corresponding neutral (NHC)PdX2(PR3) ones 132−133. The PEPPSI precatalysts 101−112 have been reported for the cross-coupling of aryl chlorides with phenylboronic acids in water at 1 mol % of catalyst loading. A few more examples of polymer supported precatalysts for the Suzuki−Miyaura crosscoupling reactions are known.000 for the coupling of p-bromo acetophenone with phenylboronic acid. The pyrazole derived abnormal N-heterocyclic carbene precatalysts 134−135a were reported for the cross-coupling for aryl bromides and chlorides with phenylboronic acids in aqueous medium at both room temperature and at 80 °C. The precatalysts.complexes (Figures 11−12). Quite remarkably.000 for the aryl chloride substrates with phenylboronic acids. The last category represents the mixed N-heterocyclic carbene and phosphine complexes.borabicyclo[3. The precatalyst 94b performed the cross-coupling of unactivated alkyl bromide and the aryl bromide and chloride substrates with alkyl-9. The other variation of the (NHC)PdX2(PR3) type precatalysts.930 for the coupling of 4-bromotoluene with phenylboronic acid. 124−131. 116−123. these are beyond the purview of the present .005 mol %. The N/O-functionalized N-heterocyclic carbene based PEPPSI (Pyridine Enhanced Precatalyst Preparation. A few examples of chelated bis phosphine/phosphite complexes 136−137[60] and 142[61] have been reported for the cross-coupling of aryl and alkyl bromides. Notable are the N/O-functionalized N-heterocyclic carbene precatalysts 113−114 that exhibited higher turnover numbers (TON) of up to 4.[62] however.1]nonane at room temperature.600. The deactivated bromoarenes could also be efficiently coupled at a low catalyst loading of 0. the (NHC)PdX2(PR3) type precatalyst 115[56] showed superior activity exhibiting ultra-high turnover numbers (TONs) of up to 106 for the aryl bromides and of up to 6. the neutral (NHC)PdX2(PR3) and the ionic [(NHC)PdX(PR3)2]+X. Stabilization and Initiation) complexes 98−100b were found to be excellent precatalysts not only for the commonly observed Csp2–Csp2 coupling but also for the more challenging Csp3–Csp2 cross-coupling at a low catalyst loading of 0. A neutral (NHC)PdX2(PR3) type precatalyst of mixed abnormal pyrazole based N-heterocyclic carbene and phosphine ligands. which are primarily of two types namely.3.300 for the coupling of 4-bromotoluene with phenylboronic acid. b showed excellent activity for the crosscoupling of aryl bromide and chloride substrates with phenylboronic acids with the precatalyst 120 exhibiting ultra-high turnover number (TON) of up to 2.[57] 138−141[58] and 143−151.3.1]nonane). . showed high turnover numbers (TONs) of up to 18. Both normal as well as abnormal Nheterocyclic carbene precatalysts have been reported for the above two classes.a The mixed abnormal N-heterocyclic carbene and phosphine complexes of the ionic type [(NHC)PdX(PR3)2]+X. the precatalyst 97a exhibited excellent catalytic activity in the coupling of sterically hindered aryl bromides and chlorides with aryl boronic acids to yield bulky tetra-ortho-substituted biaryl products in good yields under mild reaction conditions. 132−133 have also been employed in the cross-coupling reaction.precatalysts.[59] have been reported for the cross-coupling of aryl bromide and chloride substrates with aryl boronic acids. with alkenes in the presence of a base is popularly known as the Heck−Mizoroki reaction (Scheme 7). The electron rich Pd(0) species subsequently undergoes oxidative addition followed by transmetallation of organic nucleophile from an organoboron reagent. Over the years because of its wide spread utility in complex natural product synthesis and in industrial processes. The final step involves a reductive elimination step yielding the desired cross-coupled product. Important is the knowledge of the mechanism of a reaction for the design and discovery of new catalysts. the Heck−Mizoroki reaction has grown into an important C−C cross-coupling reaction. More interestingly. Of the several views that persist of the Suzuki−Miyaura cross-coupling reaction. here too.416 Chandrakanta Dash and Prasenjit Ghosh chapter that focuses on the utility of N-heterocyclic carbene based palladium complexes in homogeneous catalysis and biomedical applications. As was the case with Suzuki−Miyaura coupling. bromides. the most commonly accepted one involve a Pd(0)/Pd(II) shuttle in its catalytic cycle (Scheme 6). Herrmann first introduced N-heterocyclic carbenes in Heck−Mizoroki reaction in . LnPd(0) R R' R X reductive elimination oxidative addition R LnPd R' LnPd R X M X R' transmetallation M R' M = organoboranes (Suzuki) organostannanes (Stille) organomagnesium (Kumada) organozinc (Negishi) organosilicon (Hiyama) amines (Buchwald-Hartwig) Scheme 6. Heck−Mizoroki Reaction The palladium-mediated coupling of aryl and alkenyl iodides. The mechanism is proposed to proceed via an active Pd(0) species. the above mechanism has been found to be generic for many similar palladium catalyzed C−C and C−N cross-coupling reactions (Scheme 6). often formed in situ from the reduction of Pd(II) precursors by a base or a phosphine ligand or an organic nucleophile etc. triflates etc. As the name suggests it was first independently discovered by Mizoroki[63] and Heck[64] in the 1970s. σ domino-Heck reactions. A bis(imidazolium) salt 154[68] was used as an ionic liquid in presence of PdCl2 for the Heck coupling of aryl halides with n-butyl acrylate. Along similar line.3-bis(mesityl)-imidazolium chloride salt 152[66] that efficiently carried out the coupling of n-butyl acrylate with bromoarenes at different palladium to the ligand ratios of 1:1 and 1:2. Another palladium(0) precatalyst 21e (Figure 1) carried out the coupling of aryl diazonium salts with various olefinic substrates. the precatalysts 163−164. A Pd(0) precatalyst 20i (Figure 1) performed the Heck coupling of 4-bromoacetophenone with n-butyl acrylate.000 for the coupling of methyl acrylate and iodobenzene. 170a and 179[73] stabilized by pyridine chelated N-heterocyclic carbene ligands exhibited high activities in the coupling reaction. the pyrimidine chelated N- . (Figure 5) 61. Subsequently. Another saturated Nheterocyclic carbene precursor 153[67] performed intramolecular Heck reaction and decarbonylative Heck coupling. Scheme 7. [(BMIm)(PF6)] salt. several reports of the application of N-heterocyclic carbenes in Heck−Mizoroki coupling have appeared over the years with many performed under “Ligand Assisted Catalysis” (LAC) conditions (Figure 13). Furthermore phosphine functionalized N-heterocyclic carbene ligand precursors. Another precatalyst 181[74] supported over a pyrazole chelated N-heterocyclic carbene ligand as opposed to the aforementioned pyridine chelated N-heterocyclic carbene ones in the 163−164.858. c (Figure 6) 69 (Figure 7) and 163−181 (Figures 14−15) have been designed. Though “Ligand Assisted Catalysis” (LAC) was quite successful in the Heck−Mizoroki coupling. π. hydro-Heck. In this regard a variety of the mono-N-heterocyclic carbene Pd(II) precatalysts namely. a multidentate N-heterocyclic carbene ligand precursor 155[69] exhibited the coupling of aryl bromides with styrene and t-butyl acrylate. Notable is a 1. The 1. Quite remarkably. the precatalyst 164b showed ultra-high turnover numbers (TONs) of up to 2. 53.Palladium Complexes of N-Heterocyclic Carbenes … 417 1995. fewer reports exist of Pd(0) ones. there exists comparatively a lot more examples of welldefined Pd(II) precatalysts for the cross-coupling reaction than the palladium(0) ones. It is noteworthy that among well-defined palladium precatalysts. Interestingly enough. However. Quite significantly. A new class of efficient triphenylarsinyl-functionalized N-heterocyclic carbene based precatalysts 157−159a have been tested for the Heck. 170 and 179 complexes exhibited good activity in an ionic liquid medium of 1-butyl-3-methylimidazolium hexafluorophosphate.[65] even three years earlier than that he did the same for in Suzuki−Miyaura coupling in 1998. numerous attempts have also been made towards employing well-defined Pd(0) and Pd(II) complexes in the cross-coupling reaction.3dialkylperhydrobenzimidazolinium chloride salts 23−27 (Figure 3) performed the coupling of aryl bromides with styrene in good to excellent yields. 156[70] and 160−162[71] in presence of Pd(dba)2 exhibited the Heck coupling of a wide array of aryl bromides and iodides with n-butyl acrylates in excellent yields. Specifically. Similarly the precatalysts 203−204 showed high turnover numbers (TONs) of up to 77.209 and trans. 83–86. Similar type of o/m-xylyl linked imidazole derived precatalysts 220–226a.[87] (Figure 18) 234 (Figure 19) and 243–254[88] (Figure 20) have been designed as precatalysts for the Heck–Mizoroki C−C cross-coupling reactions. A homoleptic palladium precatalyst 205[84] showed ultra-high turnover numbers (TONs) of up to 8. a showed excellent activity for the coupling of aryl halides and n-butyl acrylate.000 for the coupling of n-butyl acrylate and iodobenzene. (Figure 16) 220–227. A precatalyst 165 exhibited very high turnover numbers (TONs) of up to 5. The N-methylated benzimidazole derived precatalysts 209–216[89] performed the Heck–Mizoroki arylations of t-butyl acrylate. led to significant increase in the turnover numbers (TONs) to up to 88.418 Chandrakanta Dash and Prasenjit Ghosh heterocyclic carbene precatalysts[75] 66 (Figure 6) and 175−178 (Figure 15) and a pyrazole chelated N-heterocyclic carbene precatalyst 180[76] (Figure 15) efficiently performed the Heck−Mizoroki couplings. the bis-N-heterocyclic carbene ones 182−256 (type B. a.08 x 108 for the cross-coupling of phenyl iodide and styrene. a cationic amine tethered bis-Nheterocyclic carbene precatalyst 184 exhibited the high turnover numbers (TONs) of up to 34.000. Apart from the mono-N-heterocyclic carbene precatalysts. It is worth noting that both the cis. c The related cis-carboxylate palladium precatalysts 214–216b showed high activities for the coupling of aryl halides and t-butylacrylate. In this context worthy of mention are the six-membered cyclic diaminocarbene complexes 182−183[83] that exhibited extremely high turnover numbers (TONs) of up to 9.000.000 for the coupling of an activated 4bromoacetopheneone substrate with styrene. c Several other chelated cis-(NHC)2PdX2 type complexes namely.800. Quite significantly. A series of palladium precatalysts 191−201[86] of CNC-pincer ligand containing two N-heterocyclic carbene moieties connected to a pyridine core showed excellent performance in the Heck–Mizoroki reactions.97.[79] The mixed β-diketonato N-heterocyclic carbene complexes 166−167[80] and an acetate bridged dimer of the type 174[81] exhibited good cross-coupling activities. (Figure 8) 89.700 in the coupling of t-butylacrylate and 4-bromoacetophenone. the precatalyst 187 exhibited the turnover numbers (TONs) of up to 13. . the precatalysts 197 and 202 were found to be thermally stable thereby facilitating the Heck–Mizoroki olefination of aryl chlorides at a high temperature. The precatalysts 184−186[85] performed the Heck-Mizoroki coupling of t-butylacrylate and aryl halides.000 after due optimization of the reaction conditions.210 isomers were equally active in the cross-coupling reaction.000 for the coupling of 4bromoacetophenone with n-butyl acrylate. Several benzothiazoline based palladium precatalysts 168−169 and 173 showed the high catalytic activity for the coupling of aryl bromides with t-butyl acrylate. Of special mention are the o-xylyl linked alkoxy benzimidazole derived precatalysts 83–86 that showed very high turnover numbers (TONs) of up to 1.[82] Variation of the substituent from a methyl group in 187 to a phenyl group in 188. (Figure 9) 189–190.33. A related variant 202c in the form of a CCC-pincer ligand was also found to be active in the cross-coupling reactions. A new class of mixed N-heterocyclic carbene-palladacycle precatalysts 165[77] and 171[78] was reported for the cross-coupling reaction (Figure 14). Quite interestingly. Figure 4) have been extensively studied for the cross-coupling reaction (Figures 16−20). A highly air and moisture stable precatalyst 171 exhibited good to excellent yields for coupling of functionalized aryl and heteroaryl bromides and iodides with olefins. 7-BuO (84) 85 86 Figure 8. CH2CONHCH2Ph (73) CH2mesityl (80) 81 BuO N N N Pd Cl N BuO BuO N N N Pd N Br Br BuO BuO BuO BuO N N N Pd N Br Br OBu N OBu BuON N Pd N OBu Br Br BuO 82 5. COOH (88) 89 5. The chelated cis-(NHC)2PdX2 type 241[90] and the non-chelated (NHC)2PdX2 type 255[91] precatalysts derived from chiral amines exhibited good catalytic activity in the Heck– Mizoroki arylation reactions. An oxazoline derived trans-(NHC)2PdX2 type precatalyst 235[92] was found to be less active in the cross-coupling reaction.Palladium Complexes of N-Heterocyclic Carbenes … O R N N R' Cl Pd Cl N R R' N S S N O N X Pd X N N Cl Pd Cl N N O O N N R O O N Pd Cl N N R N N Cl Pd Cl N N 419 R R R = t-Bu. CH2CONHCH2Ph (72). n-Bu (79). 4.6-BuO (90). R = CH2Ph. . O2CCF3 (75) R = mesityl (76).6-i-Pr2C6H3 (77) R = CH2Ph (78). 2.7-BuO (91) Me N N N Cl N Boc Ph Pd Ph Boc N Cl N N N Me 92 93 H Me N Pd Cl H N N Me Me N Cl H Figure 9. X = Br (74). 4.6-BuO (83). R' = CH22-(OMe)C6H4 (71). N O N Pd Br HO N N R N R Br N N Br Pd Br N N BuO N N I Pd BuO I N OBu N OBu R = COOEt (87). The non-chelated (NHC)2PdX2 type precatalysts 236–237[93] showed good catalytic activities in double Heck– Mizoroki coupling reactions with aryl dibromides yielding diacrylates. R = i-Pr. 6.type. R = CH2OMe. X = COOH.3.-Me4C6H (102).000 for the coupling of iodobenzene and n-butyl acrylate.000 while a related precatalyst 218 showed up to 1.6-Me4C6H. X = X'' = H (108).6-Et2C6H3 (95). X = X' = H (109). The other class of neutral (NHC)PdX2(PR3) type precatalysts include the 115b 124–125.3. R' = 2. notable is the precatalyst 124 that exhibited extremely high turnover numbers (TONs) of up to 1.5. Quite significantly. R' = CH22-(OMe)C6H4. b 136−137and 257–265a belong to the cationic [(NHC)PdX(PR3)2]+X. R' = CH2CONH Bu.80.6-i-pentC6H3 (97) R = CH2Ph. X = COOH.000.5. R' = 2.-Me5C6 (103) R N N R' R = CH2OMe.7-BuO (114) Figure 10.[95] (Figures 21–22). X' = X'' = H (104). several mixed N-heterocyclic carbene (NHC) and phosphine precatalysts namely. 124–125 (Figure 11).3. R = 2-(OH)C6H10. 2.6-Me5C6. R' = mesityl (101). R = CH2OMe.3.6-Me5C6. Most of these palladium precatalysts mainly fall into two categories (i) the cationic [(NHC)PdX(PR3)2]+X. 136–141. R = CH2OMe.700. X = X'' = H (105). 206–207a. R = t-Bu. .5. R' = 2. Lastly. efficiently performed the cross-coupling reaction in good to excellent yields. X' = COOH.3.5. R' = 2.000 for the cross-coupling of iodobenzene and n-butyl acrylate.3. R' = mesityl.713.6-Me4C6H. X = COOH.type complexes and (ii) the neutral (NHC)PdX2(PR3) ones.3. The PEPPSI (Pyridine Enhanced Precatalyst Preparation. R' = 2.000 in the coupling of phenyl iodide with styrene. X' = X'' = H (107). R' = mesityl. the precatalyst 217a showed an extremely high turnover numbers (TONs) of up to 9. X' = COOH. Among these. X = X' = H (106).3. X'' = COOH. X'' = COOH. A dicationic palladium precatalyst 242[94] showed turnover numbers (TONs) of up to 106 and a turnover frequency (TOF) of up to 5 x 104 h-1 for the coupling of n-butyl acrylate and aryl halide substrates. (Figure 11) 138–141 (Figure 12) and 266–268a complexes. X = Cl (99). The palladium complexes 116–123. R' = mesityl. X'' = COOH. R' = 2.6.4. X = Br (100) t R = CH2OMe. R = CH2OMe. 4.000.4.500 h-1. exhibited turnover numbers (TONs) of up to 1. The precatalysts of the type (NHC)2Pd(Me)Cl. Another precatalyst 256 of the [(NHC)PdCl][PdCl3] type. R = CH2OMe. X' = X'' = H (110). 2.5. R = CH2OMe.6-Me5C6.5.6-i-Pr2C6H3 (94). Stabilization and Initiation) themed ones supported over functionalized benzimidazole N-heterocyclic carbenes namely 113–114 exhibited high turnover numbers (TONs) of up to > 1. R' = 2. R' = 2. X = Cl (98).420 R Cl N Pd N R Cl N Cl Chandrakanta Dash and Prasenjit Ghosh R R N N R' R' X Pd X N N N Br HOOC Pd N Br HOOC R = 2. (Figure 12) and 257–276.6-Me4C6H.4. X' = COOH. R' = CH2Ph. R = CH2OMe.6-BuO (113). mesityl (96).800. the cationic precatalyst 137 of a Nheterocyclic carbene derived PCP-pincer ligand showed ultra-high turnover numbers (TONs) of up to 56. a. 115–123b (Figure 11). R = CH2OMe. X = X'' = H (111).4.5.5. R = CH2OMe. Quite remarkably. R = CH2OMe. X = X' = H (112) Br Pd Br N X X' X'' BuO BuO N N I Pd I N Cl 5.20.000 and a turnover frequency (TOF) greater than 4. and 217–219. have been employed in the Heck–Mizoroki cross-coupling reaction. R = n-Pr (127). R = CH2Ph (130). CH2Ph (149).4-t-Bu2C6H3 (142) N N PPh2 N I Pd PR3 I t-Bu 2 2 BF4 t-Bu O P(OR)2 Pd PCy3 Cl 136 137 O Ph R3P N Pd Cl R = Ph (143). . R = CH2Ph (126). X' = Me (120) 123 BuO N N PPh3 Pd I S N R L Pd Br Br R N N PPh3 Pd I I R PPh3 N N Pd I OTf BuO I PPh3 5. X' = H (119). X = Me. 4. X = CH. Cl N Ph3P Pd Cl N PPh2 Ph3P N Pd N C Me R = Ph (138). L = PPh2Py. L = PPh2Py. X = Me (122) Ph3P Pd PPh3 Cl Me N X BF4 Me N BF4 421 Pd Cl Cl Pd PPh3 Cl 115 X = H. R =n-Pr (131) R = Ph (132). L = PPh3. Me (135) Figure 11. X' = H (118). X' = NMe (117) BF4 X' X Ph3P N Me Ph3P Pd PPh3 Cl X = H (121). CH2C10H7 (148).Palladium Complexes of N-Heterocyclic Carbenes … BF4 X' i-Pr Ph3P N N i-Pr Ph3P X Pd PPh3 Cl X = NMe. Me (133) R = Ph (134). X = H. CH23-(OMe)C6H4 (151) Figure 12. L = PCy3. L = PCy3. 2-(CH3)C6H4 (139). Cy (146) R = mesityl (147). Cy (140). R = n-Pr (129).7-BuO (125) L = PPh3. R = CH2Ph (128).6-BuO (124).CH24-(F)C6H4 (150). Cy (144) N Cl NHPh Ph R3P N Pd Cl N Cl O NHPh N R N Pd P Ph Ph Cl Cl R = Ph (145). t-Bu (141) R = 2. X' = CH (116). [98] .g.[97] However. the reaction’s wide spread utility is largely plagued by several major limitations like that of the toxicity issues with tin as a metal and the difficulties associated with removing the metal from the final reaction mixture. The last step involves the base assisted elimination of HX from the palladium(II) complex. which reacts with an olefin to yield a palladium(II) alkyl complex. regenerating the starting palladium(0) active species. The mechanism initiates with an oxidative addition of an aryl or alkenyl halide on a catalytically active palladium(0) species to generate a palladium(II) intermediate. Stille Cross-Coupling Reaction A convenient protocol for biaryl synthesis alongside the Suzuki−Miyaura and Hiyama couplings is the Stille reaction that involves a C−C cross-coupling of aryl halides with organostannens (Scheme 5).d.[96] that were employed under heterogeneous catalysis conditions and hence they fall outside the scope of the present discussion. The Nheterocyclic carbenes were first introduced by Herrmann in the Stille coupling in 1999.422 Chandrakanta Dash and Prasenjit Ghosh Scheme 8. thus. In addition to the large body of palladium precatalysts discussed above there exist a handful of examples of polymer supported ones for the Heck−Mizoroki cross-coupling reactionb. The palladium(II) alkyl complex then undergoes β–hydride elimination to form the desired cross-coupled product. The mechanism of Heck–Mizoroki cross-coupling reaction involves the Pd(0)/Pd(II) states in its catalytic cycle (Scheme 8). . Figure 14.Palladium Complexes of N-Heterocyclic Carbenes … 423 Figure 13. 424 Chandrakanta Dash and Prasenjit Ghosh Figure 15. . Figure 16. CF3 (215). X= I. . X= O2CCF3. R = Me. R = i-Pr. Figure 18. X = I. trans (210). Me (207) RR N N Cl Pd Cl N N N R X N Pd X N N R N N N O Pd N O O R R O Me N N R Me Pd Cl R N N Me 208 R = Me. cis (213) R = Me (214). X = I. trans (211). R = CH2CO2Me (219) Figure 17. X= Br. R = CH2Py (218).Palladium Complexes of N-Heterocyclic Carbenes … 2 N N Me I Pd I N N Me N N Me I Pd I N N Me N N 203 204 N N N Pd N X N Me N N X 2 BF4 Me N Me Pd Cl N Me Me N 425 X X 205 X = H (206). CF2CF3 (216) R = CH2Ph (217). R = i-Pr. R = i-Pr. cis (209). trans (212). g. Several in situ generated palladium precatalysts obtained from the reaction of the N-heterocyclic carbene ligand precursors. furan-. tetrabutyl ammonium fluoride (TBAF). and thiazole-based organostannanes. were reported for the coupling of phenyl. activated the organotin reagent towards the transmetallation step via the formation of an anionic hypervalent stannate intermediate. (Figure 23) and a metal precursor.[100] . the addition of a fluoride salt e.426 Chandrakanta Dash and Prasenjit Ghosh Figure 19. 277−279.or vinyltrialkylstannanes with non-activated aryl chlorides and bromides. pyrrole-. Quite interestingly so. The mixed N-heterocyclic carbene and phosphine precatalysts 138−141. Pd(OAc)2. Figure 20. Stabilization and Initiation) themed precatalyst 97 (Figure 10) performed for the cross-coupling of a variety of challenging aryl or heteroaryl halides with thiophene-.[99] A well defined PEPPSI (Pyridine Enhanced Precatalyst Preparation. (Figure 12) performed the cross-coupling of aryl halides with PhSnBu3 in good to excellent yields. transmetallation and reductive elimination sequences (Scheme 6).[101] . The Stille coupling exhibits the same catalytic cycle frequently observed for the other palladium mediated C−C cross-coupling reactions involving the oxidative addition.Palladium Complexes of N-Heterocyclic Carbenes … 427 Figure 21. Figure 22. [106] The mono-N-heterocyclic carbene precatalyst 280 (Figure 24) of the type [(NHC)Pd(μ-Cl)Cl]2 exhibited high activity for the cross-coupling of aryl chloride substrates with Grignard reagents.3-bis(mesityl)-imidazolinium tetrafluoroborate 282 (Figure 25) and a palladium(0) precursor.e.[107] The PEPPSI (Pyridine Enhanced Precatalyst Preparation. the precatalyst 94 performed the coupling even at a low temperature i. i. in which an in situ generated palladium precatalyst 277 was employed for the coupling of aryl Grignard reagents with aryl halide substrates. a well-defined palladium(0) naphthoquinone complex 21 (Figure 1) performed the cross-coupling of aryl magnesium bromide with alkyl chlorides under ambient conditions at room temperature.[111] A well-defined palladium precatalyst 94 efficiently carried out the coupling of alkyl or aryl halides and sulfonates with alkylzinc bromide or arylzinc chlorides at room temperature in the presence . There only exists a handful of examples of well-defined Pd(0) and Pd(II) Nheterocyclic carbene complexes for the Kumada–Tamao–Corriu cross-coupling reaction.[110] Another the N-heterocyclic carbene ligand precursor 277 in presence of Pd2(dba)3 exhibited much higher conversions for the coupling of functionalized alkyl bromides and alkylzinc reagents at room temperature in the absence of any organozinc activator like that of N-methylimidazole (NMI).and sulfur-based heterocycles but also carried out the coupling of sterically demanding partners. In particular.[109] So far only a few examples of palladium N-heterocyclic carbene mediated Negishi coupling have been reported. Stabilization and Initiation) themed precatalysts 94−96 (Figure 10) and 281 (Figure 24) of the type C (Figure 4) also performed the coupling of more challenging ortho-substituted and heterocyclic aryl halide substrates with Grignard reagents under ambient conditions. The Kumada–Tamao–Corriu coupling goes through the commonly observed catalytic cycle of a palladium mediated C−C cross-coupling reaction (Scheme 6).[104] The utility of N-heterocyclic carbenes ligands in the Kumada–Tamao–Corriu crosscoupling was first reported by Nolan[105] in 1999. the precatalyst 280 not only showed functional group tolerance towards nitrogen. An in situ generated palladium precatalyst formed from the reaction of N-heterocyclic carbene ligand precursor. Pd2(dba)3. at -20 °C. 1. exhibited low activity for the coupling of a alkyl bromide with a organozinc reagent in the presence of a stoichiometric amount of N-methylimidazole (NMI) as an organozinc activator. Interestingly.428 Chandrakanta Dash and Prasenjit Ghosh Kumada–Tamao–Corriu (KTC) Cross-Coupling Reaction The nickel. with alkenyl and aryl halides or triflates is popularly known as the Kumada–Tamao–Corriu cross-coupling reaction (Scheme 5). Murahashi reported the use of a palladium catalyst for the coupling reaction. The first cross-coupling of Grignard reagents with alkenyl or aryl halide substrates using nickel was reported independently by Kumada and Tamao[102] and Corriu[103] in 1972. the Grignard reagents. Later in 1975.or palladium catalyzed cross-coupling of organomagnesium compounds.e.[108] Quite significantly. Negishi Cross-Coupling Reaction A rather close variant of Kumada–Tamao–Corriu cross-coupling reaction is the Negishi reaction that involves the C−C cross-coupling of organozinc reagents with organic halides or triflates catalyzed by nickel and palladium (Scheme 5). Figure 25.[113] Figure 23. .[112] The catalytic cycle of Negishi coupling resembles that of the Kumada–Tamao–Corriu coupling reaction (Scheme 6).Palladium Complexes of N-Heterocyclic Carbenes … 429 of LiCl or LiBr as an additive. Figure 24. available for the construction of biaryl frameworks. easy availability. The Sonogashira cross-coupling provides a direct and convenient access to conjugated “enyne” and “arylalkyne” skeletons common in many natural products. The now-popular PEPPSI (Pyridine Enhanced Precatalyst Preparation.[119] The most widely accepted Sonogashira protocol relies on using Cu salts as co-catalysts in a basic medium usually provided by amines. this reaction is similar to the Suzuki–Miyaura and the Stille couplings. Quite surprisingly. or alkyl halides or pseudohalides (Scheme 5). A major challenge however lies in enhancing the nucleophilicity of the inherently inert organosilicon reagents that arise out of very less electronegativity difference existing between Si and C atoms.[115] In this regard various anionic activators like F-. A N-heterocyclic carbene ligand precursor 277 in presence of Pd(OAc)2 under “Ligand Assisted Catalysis” (LAC) conditions performed the coupling of aryl bromides and chloride substrates with PhSi(OMe)3 in presence of a fluoride coinitiator.4-triazole 287−288 derived N-heterocyclic carbenes efficiently catalyzed the Hiyama coupling of a wide variety of aryl halides with organosilicon reagents like PhSi(OMe)3 and (CH2=CH)Si(OMe)3 under fluoride-free conditions but instead using inexpensive OH− anion as an anionic activator. In terms of utility. pharmaceuticals and engineered materials. but differs by using relatively inert organosilicon nucleophiles that require an activating agent like a fluoride ion or a base for the coupling to occur. The low cost. .[116] A well-defined mono-N-heterocyclic carbene palladium precatalyst 66a showed high activity towards the cross-coupling of PhSi(OMe)3 with aryl chloride and bromide substrates in presence of tetrabutyl ammonium bromide (TBAF) as a fluoride coinitiator.430 Chandrakanta Dash and Prasenjit Ghosh Hiyama Cross-Coupling Reaction The Hiyama coupling[114] is a palladium mediated C−C cross-coupling of organosilanes with aryl. Stabilization and Initiation) themed precatalysts of the type trans−(NHC)PdX2(pyridine) 283−288[117] (Figure 26) based on both the imidazoline 283−286 and 1.have been effectively used to increase the nucleophilicity of the organosilicon reagent by facilitating coordination of the activating anion to the silicon center and thereby resulting in a more nucleophilic anionic pentacoordinated organosilicon reagent. OH. alkenyl.and OR.2. agrochemicals. environmentally benign nature. The fluoride anion or the base present in the reaction medium activates the organosilicon reagent thereby making it more amenable for transmetallation. reagent stability and the functional group tolerance of the organosilicon reagents make Hiyama coupling an enticing option in organic synthesis. The Hiyama coupling too follows the commonly observed palladium mediated C−C cross-coupling mechanistic pathway (Scheme 6). Sonogashira Cross-Coupling Reactions The palladium mediated coupling of terminal alkynes with aryl or vinyl halides is popularly called the Sonogashira coupling (Scheme 9)[118] and as the name suggests it was first reported by Sonogashira and Hagihara in 1975. the utility of N-heterocyclic carbenes in Hiyama coupling has severely lagged behind than the other contemporary palladium catalyzed C−C cross-coupling reactions. Subsequently the various reports have appeared of the application of Nheterocyclic carbenes in Sonogashira coupling. The Sonogashira coupling calls for stringent anaerobic conditions as the trace amounts of oxygen or even an oxidizing environment can yield unwanted homo-coupled products by Glaser coupling. .[122] Several palladium well-defined precatalysts have been designed for the Sonogashira coupling.[120] The air and moisture sensitivity of Sonogashira coupling primarily arises due to the formation of a Cu−acetylide intermediate under the catalysis conditions. A N-heterocyclic carbene ligand precursor 278 in presence of [(π-allyl)PdCl]2 performed the coupling of alkyl bromide and iodide substrates with terminal alkynes. The palladium precatalyst of the type (NHC)PdX2 292[126] and of the type (NHC)2PdX2 293−296[127]. Another palladium precatalyst 291[124] performed the Sonogashira coupling under analogous conditions.Palladium Complexes of N-Heterocyclic Carbenes … 431 Figure 26. efficiently carried out the coupling of a wide variety of aryl bromides and iodides with terminal acetylenes (Figure 27). The use of N-heterocyclic carbenes in Sonogashira coupling was also first reported by Herrmann in 1998.and iodoarenes with terminal acetylenes in the presence of CuI and PPh3 (Figure 27).[125] The precatalyst 289 showed excellent chemoselectivity and functional group tolerance in the cross-coupling reaction.[121] Another interesting example is the coupling of trimethylsilylalkynes with deactivated bromoarenes and chlorobenzene by a in situ generated catalyst from reaction of the N-heterocyclic carbene precursor 152 (Figure 13) and Pd(OAc)2. Interestingly enough. achieving Cu-free condition is a key challenge confronting Sonogashira coupling today. a palladium precatalyst 289 of a bioxazoline-derived N-heterocyclic carbene ligand catalyzed the coupling of primary and secondary alkyl halides with alkynes. Thus. a mono-N-heterocyclic carbene bound precatalyst 290[123] carried out the coupling of bromo. Scheme 9. Quite significantly. showed higher activity compared to the (NHC)PdX2(pyridine) type ones. for which the coupling proceeds via a commonly observed Pd(0)/Pd(II) shuttle involving oxidative addition of aryl halide to a palladium(0) active species followed by coordination .432 Chandrakanta Dash and Prasenjit Ghosh Figure 27. Along the same line of thought. 98 (Figure 10) and 297. 293−294. 295−296 did the same under both the Cu-and amine-free conditions.2-a]pyridine based abnormal N-heterocyclic carbene ligands exhibited superior activity than those based on the normal N-heterocyclic carbene ligands. the precatalysts of the type (NHC)2PdX2. (Figure 27) under analogous conditions. It is worth noting that the abnormal N-heterocyclic carbenes by virtue of the carbene center being adjacent to a single heteroatom as opposed to two heteroatoms in the case of normal N-heterocyclic carbenes are more electron rich and hence more σ-donating than the normal N-heterocyclic carbenes. however. The higher conversions observed for the (NHC)2PdX2 type precatalysts 293−294 thus upholds the hypothesis that more electron rich metal centers act as better catalysts presumably by facilitating the aryl halide oxidative addition step. The PEPPSI themed precatalysts 283−288 (Figure 26) and 297−303[128] (Figure 27) were also active for the Sonogashira coupling of aryl bromides and iodides. (i) one for the production of the Cu-acetylide species and (ii) the other for its coupling with the desired aryl or alkyl species (Scheme 10). the precatalysts 293−294performed the Sonogashira coupling under amine free conditions whereas the precatalysts 292. Particularly. ruled out in the case of the Cu-free Sonogashira coupling.e. 300−303[128] (Figure 27) supported over the more σ−donating imidazo[1. The transmetallation of copper acetylide to palladium is believed to be the rate-determining step. The proposed mechanism for the Sonogashira coupling in presence of a copper cocatalyst involves two independent cycles i. the trans−(abnormal-NHC)PdX2(pyridine) type palladium precatalyst. Quite interestingly. The above mechanism is.. (I). Arylation of Enolates The arylation of enolates is a powerful strategy for synthesizing a variety of high-value chemicals like. A handful of examples of N-heterocyclic carbenes in arylation of enolates have been reported. nitriles and amides from simple aryl halides. α-arylated ketones.Palladium Complexes of N-Heterocyclic Carbenes … 433 and deprotonation of alkynes in the presence of a base. . esters. Arylation Reaction The palladium N-heterocyclic carbene mediated arylation reaction observed in the literature can be classified into the following types. The enantiomerically pure imidazolium triflates 304−306[129] (Figure 28) in presence of palladium precursors like Pd(OAc)2 or Pd2(dba)3 have been employed in the synthesis of oxindoles by asymmetric α-arylation of amides. Scheme 10. and which subsequently leads to the desired Sonogashira product by a final reductive elimination step (Scheme 11). A bis-(NHC)2PdX2 type precatalyst 320 (Figure 20) has been reported for α-arylation of amides. Other N-heterocyclic carbene precursors. 153 and 277. The arylation occurred at the α-position to the carbonyl group with preference for the less sterically hindered carbon atom in case of the .3-di-(1-adamantylmethyl)-substituted saturated N-heterocyclic carbene precursor 307[131] in presence of Pd(OAc)2 carried out the α-arylation reaction enantioselectively showing high enantiomeric excess (ee) but low yields. in presence of Pd(OAc)2 have been used in the inter.434 Chandrakanta Dash and Prasenjit Ghosh Scheme 11. The reaction though proceeded in excellent yields but exhibited low enantioselectivity (Scheme 12). a sterically demanding 1. Scheme 12. iodides. Mono-N-heterocyclic carbene palladium precatalysts of the type (NHC)Pd(allyl)Cl 34−37[133] (Figure 5) and 313 and the palladacycle 64[134] (Figure 6) performed the arylation of simple ketones with non-activated aryl chlorides.[130] Interestingly. In this regard notable is a series of well-defined mono-N-heterocyclic carbene precatalysts 314−316[132] (Figure 28) that exhibited high ee and high yields in the asymmetric α-arylation of amides. and triflates in the presence of NaOtBu (Scheme 13). bromides.and intra molecular α-arylation of amides. These conditions allowed the formation of five. The direct arylation of alkynes with aryl halides provides another convenient alternative to biaryl skeletons (Scheme 15). (Figure 23) and 308−311[137] with Pd(OAc)2. the monoortho-substituted products were formed for the aryl chlorides while di-ortho-substituted products were observed for aryl bromides.and six-membered rings bearing ether. Direct Arylation Reactions Direct arylation reaction is an important method for constructing biaryl frameworks. The utility of N-heterocyclic carbenes in the direct arylation reaction has thus attracted attention lately. Another interesting method for the o-arylation of benzaldehyde derivatives was reported with the in situ generated palladium precatalyst from the reaction of N-heterocyclic carbene precursors 279. (II).Palladium Complexes of N-Heterocyclic Carbenes … 435 unsymmetrical ketones. another close variant of the type (NHC)Pd(acac)Cl. or alkyl tethers. amide. In this regard the well-defined precatalysts 319 and 321−330 . Along the same line. O R R' Scheme 13. 317−318. probably due to the preventive effect on catalyst decomposition at high reaction temperatures.[135] was effective for the α-arylation of ketones. amine. + X Ar Pd-NHC complex R O Ar R' Scheme 14. Notable is the precatalyst 312[136] (Figure 28) that showed high activity for the intramolecular direct arylation with aryl chlorides (Scheme 14). Scheme 15. More interestingly. The use of N-heterocyclic carbene ligands as additives led to significant enhancement of reactivity. [138] The other well-characterized precatalysts that include the PEPPSI (Pyridine Enhanced Precatalyst Preparation. a Ph N N Pd Ph Cl Cl Ph i-Pr N O 319 320 N O Ph Ph N N i-Pr I Pd I i-Pr O N N O i-Pr Ph Cl Pd N Cl N Ph Cl Pd N Ph Cl N N N 321 322 Ph N N R X Pd X R' PL3 Ph Cl N Pd Cl N PL3 R2P I Pd I N N Cy2P N Pd N N N 2 2 BF4 R = CH2Ph. X = Cl. R = R' = CH2Ph.and stereoselectivities for the hydroarylation of alkynes at a low catalyst loading of 0.[140] Another efficient precatalyst 332 exhibited high activity along with high chemo.[139] Later. and the mixed N-heterocyclic carbene and phosphine precatalysts. L = Ph (325) L = Ph (326). X = Br. Hydroarylation Reactions Hydroarylation of alkynes is a highly atom economic protocol that makes use of inexpensive starting materials like arenes. 321 and 322. . L = Cy (323).1 mol %[141]. L = Ph (324). Cy (329) 330 Figure 29. the N-heterocyclic carbene based palladium precatalysts 63 (Figure 6) and 331 (Figure 30) have been employed for the hydroarylation of ethyl propiolate that produced stilbene derivatives at room temperature (Scheme 16). X = Cl. R = R' = CH2Ph. Stabilization and Initiation) themed precatalysts. a. 323−330. carried out the direct arylation alkynes with phenyl halides. The mixed N-heterocyclic carbene and phosphine precatalysts 323−330 exhibited the superior activity compared to the PEPPSI themed ones 321−322 of the type (NHC)PdCl2(pyridine) and also to the (NHC)2PdCl2 type 319 precatalyst for the direct arylation of alkynes with aryl halides. R' = CH2CONHPh. Cy (327) R = Ph (328).436 Chandrakanta Dash and Prasenjit Ghosh (Figure 29) efficiently performed the arylation of alkynes with aryl halide substrates. Fujiwara first reported the reaction of simple arenes with alkynes in trifluoroacetic acid (TFA) yielding stilbenes catalyzed by Pd(OAc)2. Due to its wide spread applicability. O + OEt R Pd-NHC complex R COOEt + COOEt COOEt R Scheme 16. the C−N bond forming reaction are of great importance to both industry and academia. atom economy. and the product value. .Palladium Complexes of N-Heterocyclic Carbenes … 437 Figure 30. Scheme17. C−N Bond Formation Reaction The palladium mediated C−N bond forming reactions are fundamentally important to organic synthesis like the C−C cross-coupling ones and these reactions mainly are of two types (i) the Buchwald–Hartwig amination reaction (Scheme 5) and (ii) the hydroamination reaction (Scheme 17). Several other N-heterocyclic carbene precursors 333−337 (Figure 31) have been reported for the amination reaction. b The in situ generated bisimidazol based precatalysts. bromides and iodides. sulfonamides. a Figure 31. the Buchwald−Hartwig reaction involves the coupling of aryl halides.438 Chandrakanta Dash and Prasenjit Ghosh Buchwald−Hartwig Amination Reaction First discovered independently by Buchwald[142] and Hartwig[143] in 1995. The palladium precatalysts of bulky tertiary phosphines are often used in this transformation. The N-heterocyclic carbene precursor 277[145] in presence of Pd2(dba)3 exhibited good to excellent conversions for the amination of aryl chlorides.[147] Quite significantly.000 for the amination of aryl chlorides. 346. amides. Interestingly.[144] As the N-heterocyclic carbenes are often regarded as the “phosphine substitutes” their utility in the C−N bond forming reaction is increasingly becoming popular. the N-heterocyclic carbene precursor 333 in presence of Pd(dba)2.[146] The more electron rich N-heterocyclic carbene precursor [153] performed the N-arylation of indoles. Several well-defined palladium(0) and palladium(II) precatalysts have been employed for the Buchwald−Hartwig amination reaction.1]heptane with aryl and heteroaryl chlorides and bromides. imines. an N-heterocyclic carbene precursor 277 in presence of Pd2(dba)3 carried out the amination of aryl chlorides with benzophenone imine. obtained from the reaction of 333−334 with Pd2(dba)3.2. triflates and tosylates with aryl or alkyl amines. the precatalyst 15 and a mixed N-heterocyclic carbene and phosphine palladium(0) precatalyst. showed excellent conversions for the amination . showed turnover numbers (TONs) of up to 5. Specifically. The palladium(0) precatalysts 10−11 (Figure 1). were successfully employed in coupling 7-azabicyclo[2. 15−16b (Figure 1) and 346[148] (Figure 32) have been reported for the amination reactions of aryl chloride substrates. b. nitrogen-containing heterocycles and ammonia. The N-heterocyclic carbene-palladacycles 343−344b showed Buchwald−Hartwig amination for a range of unactivated aryl chloride substrates. secondary. Subsequently. Quite remarkably. Stabilization and Initiation) themed precatalyst 94 (type C. Hiyama.Palladium Complexes of N-Heterocyclic Carbenes … 439 reactions of aryl chlorides with the primary. the palladium(II) counterparts have been rather extensively studied. b 52a (Figure 5). Contrary to the fewer reports of well-defined palladium(0) complexes that exist. the cinnamyl complexes 52a and 345 showed excellent activity in the Buchwald−Hartwig amination. a The catalytic cycle proposed for the Buchwald−Hartwig amination reaction is analogous to that of the other palladium mediated C−C cross-coupling reactions like.[153] The catalysis originates with the oxidative addition of aryl halide or pseudohalide to a palladium(0) active species followed by the coordination of the amine to the metal. Figure 4) was effective for the amination reaction of electron-deficient. Quite significantly. 64 (Figure 6). Stillle. In this context several mono-N-heterocyclic carbene palladium(II) precatalysts 35. the PEPPSI (Pyridine Enhanced Precatalyst Preparation. the reductive elimination step yields the amine product with the regeneration of palladium(0) active species (Scheme 6). or arylamines at room temperature. 70[149] (Figure 7).[152] The mixed Nheterocyclic carbene and phosphine precatalysts 265 (Figure 21) and 347−349 (Figure 32) were found to be active for the amination reaction of bromobenzene or 2-chloropyridine with morpholine. Negishi and Kumada-Tamao-Corriu couplings involving a common Pd(0)/Pd(II) cycle. Suzuki–Miyaura. secondary and arylamines. The air and moisture stable precatalysts 317−318 (Figure 28) and 70 exhibited excellent activities for the amination of aryl chlorides and bromides with a variety of amines under mild conditions. electron-rich aryl and heteroaryl chlorides and bromides with various sterically hindered and also functionalized drug-like aryl amines. The palladium alkyl derivatives 341−342a were effective in the Buchwald−Hartwig amination reaction of aryl chlorides. alkyl. The precatalyst 345 efficiently carried out the amination reactions of a wide range of unactivated. Figure 32. neutral and activated chlorides and bromides with a variety of primary. b 37. . 338−340[150] and 341−345[151] (Figure 31) have been reported for the amination reaction. Finally. the palladium bound coordinated amine undergoes deprotonation in the presence of a base. R' = CH2Ph (352).440 Chandrakanta Dash and Prasenjit Ghosh Hydroamination Reaction Another important and also atom economic C−N bond forming reaction is the hydroamination reaction that involves the formal addition of a N−H bond across a C−C multiple bond (Scheme 17). regio. The utility of N-heterocyclic carbenes in the hydroamination reaction has received much less attention so far.[155] BF4 2 Ph N N Pd N N O t-Bu t-Bu H N t-Bu R' N 2BF4 N N R 2 2BF4 N Pd NCMe N N t-Bu MeCN Pd NCMe N N R i-Pr MeCN 350 351 R = t-Bu. R = mesityl. Hydroamination is sometime weakly exergonic or thermoneutral and therefore exhibits a very high negative entropy of the reaction making it thermodynamically less favorable. Other well-defined palladium precatalysts 351−353 of the type bis-(NHC)2PdX2 have been reported for the hydroamination of methacrylonitrile with secondary amines. R = 3. A new class of palladium precatalysts 354−355[157] of 1. the mixed N-heterocyclic carbene and phosphine precatalysts. R' = H (353) 2 i-Pr N N N R R Br Pd Br N N N i-Pr Fe N P Pd R2 N P R2 Fe 2PF6 NCCH3 R = Et (354). CH2-CH=CH2 (355) R = Ph (356).and stereoselectivities and functional group tolerance. 356−357.5-(Me2)C6H3 (357) Figure 33.[154] In this context the transition metal catalyzed hydroamination reaction assumes relevance as it facilitates catalytic C–N bond formation under amenable conditions with controlled chemo-.2. In this regard significant a the mono-N-heterocyclic carbene precatalyst 350[156] (Figure 33) that carried out the hydroamination of methacrylonitrile with piperidine.[158] exhibited high yields but low enantiomeric excess (ee). .4-triazole derived N-heterocyclic carbenes showed moderate to good conversions for the hydroamination of activated olefins under ambient conditions . for the asymmetric hydroamination of methacrylonitrile with aliphatic amines. Lastly. Specifically.[160] The precatalyst 312 carried out the oxidation of a variety of benzylic and allylic alcohols to the corresponding aldehydes and ketones exhibiting turnover numbers (TONs) of up to 1. Oxidation of Alcohols Palladium(II) catalyzed oxidation of alcohols using molecular oxygen as an oxidant is a very useful transformation in organic synthesis (Scheme 18). A detailed theoretical study on these complexes revealed that the solvent plays an important role on the reversibility of the oxygenation step.[165] In this process stoichiometric CuCl2 is used as a cocatalyst under aerobic conditions. In this reaction. The precatalysts 280[164] carried out highly regioselective reductive coupling of arylboronic esters and styrene under aerobic conditions. .000.[159] The use of palladium precatalyst of N-heterocyclic carbene in an oxidation reaction was first reported by Sigman in 2003.Palladium Complexes of N-Heterocyclic Carbenes … 441 Oxidation Reaction The oxidation reactions exhibited by palladium N-heterocyclic carbene complexes are mainly of the following two types. O R' R R' (II). Stahl[162] isolated rare peroxo and hydroperoxo derivatives of palladium that are important intermediates in the oxidation catalysis. the oxidative conditions are required for the oxidation of the alcoholic solvent to generate the active palladium(II) hydride intermediate. (i). c The oxidation reactions using molecular oxygen as terminal oxidants have been successfully applied for the kinetic resolution of secondary alcohols and to the alkene hydroarylation reaction employing boronic esters (Scheme 19). OH Pd-NHC complex R Scheme 18. the chiral palladium precatalysts 360−362[163] showed oxidative kinetic resolutions of secondary alcohols in good yields with moderate to good enantioselectivities. b Along the same line. the precatalysts 358−359[161] (Figure 34) performed the aerobic oxidation of alcohols. which reacts with alkene to yield a palladium alkyl species. Quite significantly. Subsequent transmetallation and reductive elimination yield the desired product (Scheme 17). Wacker Oxidation and Oxidative Cyclization Reactions Palladium catalyzed oxidation of terminal olefins to methyl ketones is popularly known as the Wacker oxidation and is used in the production of acetaldehyde on an industrial scale. A mixed N-heterocyclic carbene and phosphine palladium(0) precatalyst 5 (Figure 1) of the type (NHC)Pd(PR3) performed the hydrogenation of olefins. Notable is a precatalyst 70 (Figure 7) that performed the oxidation of styrenes to acetophenones (Scheme 20). Scheme 19. These have contributed to the growth of research in the area.3. t-Bu (359) R = 2. In this transformation the formation of a cationic palladium hydride intermediate is proposed and which is formed from the oxidative addition of a imidazolinium salt to a palladium(0) precursor species.6-Me4C6H (360) 361 362 Figure 34. [(NHC)Pd(allyl)Cl].[166] An in situ generated precatalyst derived from the N-heterocyclic carbene ligand precursor 152 and palladium bistrifluoroacetate Pd(COOCF3)2 exhibited efficient intramolecular Wacker-type cyclization reaction under aerobic conditions (Scheme 21). have been reported for the dehalogenation of aryl chlorides.442 i-Pr N i-Pr O R O O N i-Pr Pd O R i-Pr Chandrakanta Dash and Prasenjit Ghosh Ph Ph N R Cl Pd Cl N R Ph N R Cl Pd Cl N R N Ph N N Pd N Me I I Me N N Pd N N Me I I Me R = Me (358).[170] . b A cationic bis-N-heterocyclic carbene precatalyst 363[169] carried out the hydrogenation reaction of cyclooctene to cyclooctane (Scheme 23).[167] Reduction Reaction An in situ generated palladium precatalyst obtained from the reaction of N-heterocyclic carbene precursor 279[168] with Pd(dba)2. However. performed the dehalogenation of aryl bromides and chlorides at 100 °C (Scheme 22).5. the reaction suffers from many drawbacks like the formation of chlorinated byproducts and from the issues associated with palladium decomposition. Another well-defined complex 35 (Figure 5) of the type. R O R' R O2. R' Pd-NHC complex OH Scheme 21. .Palladium Complexes of N-Heterocyclic Carbenes … 443 Scheme 20. 80 oC Scheme 22. toluene. Pd-NHC complex 1 atm H2 i-Pr N N N N i-Pr Pd NCMe NCMe 2 2 BF4 363 Scheme 23. 42 (Figure 5) and 366−367 carried out the polymerization of functionalized norbornene namely. The palladium complexes are known to catalyze the reaction of dienes with a variety of nucleophiles. Polymerization Reactions The use of palladium N-heterocyclic carbene complexes in polymerization reactions are relatively less explored compared to the other catalysis. . secondary amines > primary amines > ammonia. the mono-Nheterocyclic carbene complex 365[176] performed the norbornene polymerization exhibiting very high activitiy of up to 108 g of polynorbornene (mol of Pd-1 h-1) in the presence of methylaluminoxane (MAO) as a coinitiator. the precatalysts 35−36[178] and 368−370 and the bis(aryloxide-N-heterocyclic carbene) precatalysts 373−377[179] performed the polymerization of norbornene and its derivatives. Quite interestingly. better chemoselectivity in terms of linear to branched product ratios were observed for the N-heterocyclic carbene precatalyst than the phosphine ones.444 Chandrakanta Dash and Prasenjit Ghosh Tsuji-Trost Alkylation Reaction Palladium catalyzed allylic substitution reaction has become a popular method of C−C bond formation along the lines of various other C−C cross-coupling reactions.[171] the use of N-heterocyclic carbene in allylic alkylation reaction was only reported as late as in 2003.173] Telomerization Reactions (I). The order of amine reactivity in the telomerization reaction was found to be as. the telomerization of amines and dienes is also an interesting transformation for the formation of short oligomers.[174] Beller first employed a mono-N-heterocyclic carbene palladium(0) complex 18d (Figure 1) for the telomerization of butadiene with alcohols (Scheme 25). In particular. Other mono-N-heterocyclic carbene precatalysts 35. 40. Quite remarkably. Nolan first employed a well-defined cationic palladium(II) percatalyst 364[175] for the telomerization of butadiene with amines under mild conditions (Scheme 26). The precatalysts 365−377 (Figure 35) have been employed in a variety of polymerization reactions. though a palladium mediated allylic substitution reaction was reported by Tsuji in 1965. (ii).[172. Telomerization of Dienes with Amines Like the telomerization of dienes and alcohols.[177] Along the same line. Telomerization of Dienes with Alcohols Telomerization is a 100 % atom economic process involving the formation of short oligomers from dienes. 5-norbornene-2-methyl acetate. The cationic bis-N-heterocyclic carbene precatalysts 371−372[180] have been reported for the copolymerization of CO and C2H4.[172] An N-heterocyclic carbene precursor 277 (Figure 23) in presence of Pd2(dba)3 was found to be active for the allylic alkylation reaction (Scheme 24). A handful of examples of N-heterocyclic carbenes in the cycloisomerization reaction have been reported.Palladium Complexes of N-Heterocyclic Carbenes … 445 Scheme 24.[182] which in the presence of Pd2(dba)3. Of particular mention is an N-heterocyclic carbene precursor 336. . Cycloisomerization Reactions The transition metal-catalyzed cycloisomerization of enyne systems is a powerful synthetic approach for the construction of intricate architectures in various target molecules[181]. OMe 2 + Pd-NHC complex MeOH + OMe Scheme 25. + Pd-NHC complex RR'NH NRR' 2 i-Pr N i-Pr N i-Pr PF6 Pd i-Pr NCMe 364 Scheme 26. carried out the bismetalative cyclization of enynes in the presence of Bu3SnSiMe3 (Scheme 27). X = Br (369).446 Chandrakanta Dash and Prasenjit Ghosh i-Pr N N Cl Pd Cl X PhPh N N Me i-Pr Pd i-Pr Cl N X R i-Pr R N N R Cl X MeCN Pd N NCMe R R R N N N 2 2X Pd 365 X = H (366). X = I (370) R = mesityl. X = PF6 (371). X = Br (368). was employed for the cycloisomerization of 1.6-dienes forming various cyclic compounds. mesityl (374) t-Bu R = Me (375). t-Bu 377 Figure 35. Quite significantly. Me (367) R = Me. R = i-Pr. Another precatalyst 378[184] was reported for the cycloisomerization of alkylidenecyclopropanes that resulted in the corresponding 1-aryl dihydronaphthalenes in very high selectivity at room temperature (Scheme 29). the cycloisomerization reactions proceeded at room temperature with complete regioselectivity yielding the desired exo-methylene-containing products (Scheme 28). Scheme 27. R = Me. i-Pr (376) Figure 35. R = i-Pr. A mono-N-heterocyclic carbene complex 367[183] (Figure 35). . Figure 28. of the type (NHC)Pd(allyl)Cl. X = BF4 (372) t-Bu t-Bu t-Bu t-Bu O Pd O t-Bu N N R R N t-Bu R N O Pd N N R t-Bu t-Bu O Pd O t-Bu N N t-Bu N t-Bu O N N N t-Bu R = Ph (373). a triazolyldiylidene derived palladium complex 384[191] (Scheme 36) was reported for the direct acylation of aryl iodides or bromides with aldehydes. In this regard notable are the chiral precatalysts 379−380[185] (Scheme 30) that performed the asymmetric conjugate addition of arylboronic acids to cyclic enones in good to high enantioselectivities. The same precatalysts 379−380[186] were also employed for the allylation of aldehydes with allyltributyltin.2-addition of boron reagents to aldehydes. .β-unsaturated N-acylpyrroles using allylboronic ester (Scheme 32). Finally. CH2=CH-CH2SnBu3 (Scheme 31).4-addition of terminal alkynes to unsaturated carbonyl compounds (Scheme 33). A 1. Addition Reactions Designing highly efficient and enantioselective palladium N-heterocyclic carbene precatalysts remain an important goal in asymmetric synthesis.Palladium Complexes of N-Heterocyclic Carbenes … 447 R R Pd-NHC complex R Mes N N Mes 378 Cl Pd Cl Mes N N Mes R Scheme 29. A mixed N-heterocyclic carbene and phosphine precatalyst 381[187] was employed for the conjugate allylation reaction of α.2′-diamine (BINAM) palladium precatalyst 383[190] (Scheme 35) was reported for the arylation of N-tosylimines with arylboronic acids in good to high enantioselectivities.[188] A thioether functionalized N-heterocyclic carbene precursor 382 [189](Scheme 34) in presence of [Pd(allyl)Cl]2 performed the 1.1′binaphthalenyl-2. was reported for the 1. An in situ generated palladium precatalyst formed from the reaction of the Nheterocyclic carbene precursor 152 with Pd(OAc)2. + SnBu3 Pd-NHC complex R OH O N Ar + Me Me Me Me O O B O Cl N N Me 381 PPh2 Pd Pd-NHC complex N Ar Scheme 32. RCHO Scheme 31. CF3 (380) Scheme 30. .448 Chandrakanta Dash and Prasenjit Ghosh O + ArB(OH)2 Pd-NHC complex O * Ar N O Me O R Pd R O N N Me O N R = Me (379). . O R H + [B] R' Pd-NHC complex R OH R' i-Pr N i-Pr N Cl PhS 382 Scheme 34. Ts ArB(OH)2 + N R Pd-NHC complex Ts Ar 2 NH R 2OTf N N Pd OH2 OH2 N N 383 Scheme 35.Palladium Complexes of N-Heterocyclic Carbenes … 449 O O R + R' Pd-NHC complex R R' Scheme 33. Another precatalyst 94 catalyzed the synthesis of indoles by sequential aryl amination and Heck coupling reactions (Scheme 38). Notable is a palladium N-heterocyclic carbene complex 385[192] (Scheme 37) that was successfully used for the domino Sonogashira and hydroalkoxylation reactions.[193] . Scheme 37.450 Chandrakanta Dash and Prasenjit Ghosh R O X + R' H Pd-NHC complex R O R' Me Cl MeCN Pd Cl N N N Me Me Cl Pd Cl NCMe 384 Scheme 36. R R Pd-NHC complex + R' H OH R R OH X RR O R' R' Me Cl N Pd Cl N N N Me Cl Me Cl Pd N 385 Scheme 37. Domino Reactions There exist only a few reports of domino reactions involving sequential C−C bond forming reactions catalyzed by palladium N-heterocyclic carbene complexes. 2-20 times greater inhibition on the proliferation of the three different commonly occurring human tumor cells namely. In this context the success of N-heterocyclic carbene primarily arises due to their strong binding nature.[198] (Figure 36) were screened for their anticancer properties. carboplatin. further brightens the prospects of the N-heterocyclic carbene compounds in cancer therapy. Hence. there exist several concerns with these metallodrugs like its effect on narrow spectrum range of cancer cells. breast cancer (MCF-7) and colon adenocarcinoma (HCT 116) cell lines than the much used metallodrug cisplatin under analogous in vitro conditions. Palladium as a metal display similar structural preferences like platinum and also exhibit promising cytotoxicity and thus provides a viable alternative to the platinum based metallodrugs like cisplatin and carboplatin. the palladium N-heterocyclic carbene complexes have made an indelible mark in chemical catalysis and are displaying promising traits in biomedical applications like in anticancer studies. and thus provides an ideal platform for designing palladium catalysts with .[197] Moreover. the cervical cancer (HeLa).[196] Hence. CONCLUSIONS In summary. the palladium complexes of N-heterocyclic carbenes 386−388.[194] Among the commonly used metallodrugs today are cisplatin. Palladium in Biomedical Application Metallopharmaceuticals are emerging as prominent players in therapeutic and diagnostic medicine these days. finding suitable alternate metallodrugs remains a key objectiveat the heart of research in this area. Detailed mechanistic studies revealed that the 387 complex arrested the cell cycle at the G2/M transition phase of the cell division. that prevents catalyst leaching by suppressing ligand dissociation. the N-heterocyclic carbenes. the discovery and development of new metallodrugs is an increasingly popular area of research in medicinal inorganic chemistry in recent times. cisplatin. low aqueous solubility. neurotoxicity and emetogenesis that constrict its broad based utility. cis-(NH3)2PtCl2. and its second generation analog. The superior activity of the palladium Nheterocyclic carbene complex 387 compared to the commonly used metallodrug. Particularly interesting is the trans-(NHC)2PdX2 type 387 complex that was found to be more effective than not only a trans-(NHC)PdX2(pyridine) type 386 complex but also exhibited ca. various toxicity issues in the form of nephrotoxicity.Palladium Complexes of N-Heterocyclic Carbenes … 451 Scheme 38. though extremely successful in catalysis.[195] However. remain largely unexplored in biomedical applications. Against this backdrop. Wang. Kaval. Denmark. K. Wong. (b).. (f). Muñiz. Org.. 1995. D. [2] [3] [4] . Nature 2008. X. Int. M.. Springer: Berlin.. 49–175. P. Van der Eycken. J. 387 388 REFERENCES [1] (a). Coates. J. Wiley and Sons: New York. Wiley-Interscience: New York.. 5094– 5115. 110. J. R.-H. Lautens. 100. 2005. Angew. Chem. Luh. I. 2000. 2007. Tsuji. 1997. E. Pure Appl.. (d). 2009. Chem. 2021−2027. E. 824–889. Chem.. M. Sottocornola. Process Res. Ed. 107. Alberico. Springer: Berlin. 107. S. 77. Hand book of Organopalladium Chemistry for Organic Synthesis.P. 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They were basically aimed at studying the effect of added ligands-modifiers on catalyst activity in chain initiation steps * A version of this chapter was also published in Selective Catalytic Hydrocarbons Oxidation: New Perspectives. It should be mentioned that in its original form. Russia The application of metal-complex catalysis opens the possibility of regulating the relative rates of elementary stages Cat–O2. Cat–ROOH. Zaikov. Zaikov Emanuel Inst. it is possible to vary the yields of target products. Inc. Nova Science Publishers. a catalyst often represents only the precursor of real catalytic particles. Studies aimed at investigation of the mechanism of action of additives were scarce. Larisa A. Matienko. whereas in homogenous catalysis. Understanding of the mechanisms of the additive’s action at the formation of catalyst active forms and mechanisms of regulation of the elementary stage of the radical-chain oxidation may apparently lead to the development of new. Larisa A. and thus control the reaction selectivity. efficient catalytic systems and selective oxidation processes.In: Homogeneous Catalysts: Types. By changing the ligand environment of the metal center or adding different activating compounds. . Russian Academy of Sciences. Mosolova and Gennady E. by Ludmila I. of Biochemical Physics. Cat–RO2 and in that way of controlling the rate and selectivity of processes of radical-chain oxidation [4]. Reactions and Applications ISBN: 978-1-61122-894-6 Editor: Andrew C. In heterogeneous catalysis. it is possible to accelerate the formation of catalytically active species and prevent or hinder the processes that lead to catalyst deactivation. the use of various modifiers was not systematic. the methods of modifying a catalyst by different additives that enhance its activity and prevent its deactivation were used rather extensively. It was submitted for appropriate modifications in an effort to encourage wider dissemination of research. By introducing various ligands-modifiers into reaction. Chapter 14 METHODS FOR ENHANCING THE ACTIVITY AND SELECTIVITY OF HOMOGENEOUS CATALYSTS IN THE OXIDATION PROCESSES * Ludmila I. Matienko. The catalyst performance is always accompanied by its deactivation. Moscow. However. At present. Moreover. 2. It is now generally agreed that oneelectron redox reactions and oxygen-centered free radical chemistry being about the oxidations in these systems are most probably the mechanisms similar to those proposed for biological oxidations by Cytochrome P-450 and methanemonooxygenase (through twoelectron oxygen-transfer processes at participation of an active high-valent metal-oxo oxidant) [12. the oxidation of the ligand by another complex cannot be realized. For example. Matienko. IMMOBILIZATION OF HOMOGENEOUS CATALYST ON HETEROGENEOUS SUPPORT FOR INCREASE IN ACTIVITY AND SELECTIVITY OF CATALYST IN THE ALKYLARENS OXIDATIONS Several studies were devoted to the processes of alkylarene oxidation in the presence of metal complexes immobilized on the surface of a polymer or mineral carrier (silica gel.2.14]. and the life of salen catalyst is prolonged [16]. The occluded catalytic complexes require a zeolite with caves or intersections. 3-methylpentane. and more recently that of Gray and Labinger. Though observed to increase. in the majority of schemes of catalytic radical-chain oxidation of hydrocarbon. into porphyrin ligand increases the stability of halogenated iron porphyrins in oxidative destruction and as result their activity [10. As a rule. ROOH homolytic decomposition) [4. The including of halogen.1.13. Zaikov (the O2 activation. the stability of such complexes remained moderate. One of the limitations of zeolites are that their tunnel and pore sizes are no larger than about 10 Ǻ [18]. the zeolite influences the formation of products by steric and electronic influences on the transition state of the reaction. they also control the entry and departure of reagents and products. such as 2-methylbutane. Larisa A. At the same time. as indicated by the low conversion of alkanes. electron-withdrawing substituents. For these . 7]. the numerous examples of various catalytic reactions are known when addition of certain compounds in small amounts dramatically enhances the reaction rate and rarely the product yield. The additives.3-dimethylbutane. the mechanisms of action of additives were not established. which are large enough to embed them. III.3-trimethylbutane. Perhalogenated iron porphyrins are known to be effective at decomposing alkyl hydroperoxides via free radicals formation [13. are prevented from deactivation. and 1.14]. substituted alkanes. 11]. Mosolova and Gennady E. are oxidized into a mixture of products due to oxidative carbon-carbon bond cleavage [11]. the O2 activation with transition metal complex was totally ignored. often being axial ligands for metal complexes.464 Ludmila I. The potential advantages of using a solid catalyst include the case of its removal from the oxidation mixture and subsequent reuse and control of catalyst reactivity through its microenvironment exerted by the support. The works of Ellis and Lyons. heterogenised in the zeolite pores. have identified the halogen-substituted metal porphyrins—catalyzed oxidation of alkanes into alcohols by dioxygen at the mild conditions (100oC) [10-13]. metal complexes. The increase in stability encapsulated salen complex arises from the protection of the inert zeolite framework. although the authors tentatively propose mechanistic explanations [9]. are considered in models. zeolite) [15-21]. making complex degradation more difficult by sterically impeding the attack to the more reactive parts of the ligand. which mimic enzyme reaction center (mono.and dioxygenase). and Cu-hydroperoxo species. 1. revealing that C–H activation occurs at both the benzylic and aromatic ring carbon atoms. The creation of a hydrophobic environment around the active site was required to circumvent the activity and sorption problems. The “neat” and zeolite-Y-encapsulated copper complexes with tri. [17] catalyzed the ethylbenzene oxidation reactions by dioxygen into the same three products. μ-η2:η2peroxo (bis-μ-oxo complexes).4.4.7triazocyclononane. in turn. The latter is significant over the “neat” complexes in the homogeneous phase. The low activity of these zeolite catalysts is connected with their high hydrophility. Often. and acetophenone (1:1:1). with a large pore Fe – ALPO-5. It is known that postsynthesis hydrothermal dealumination and other chemical treatments form defect domains of 5 to 50 nm (which are attributed to mesopores) in faujasites.7-trimethyl-1.4. However. This suggests the same reaction mechanism in both cases that these catalytic oxidations react by the same mechanism. α-phenylethyl-hydroperoxide.11-tetraazocyclotetradecane exhibit efficient catalytic activity in the regioselective oxidation of ethylbenzene using tert-butyl hydroperoxide [20]. subsequent radical reactions occur until the cyclohexyl ring is broken to form linear products that are sufficiently mobile to diffuse out of the molecular sieve. So the silica—and polymer—supported iron(III) tetrakis(pentafluorophenyl)porphyrins.10-tetramethyl-1.4.4.Methods for Enhancing the Activity and Selectivity… 465 purposes. 1. increased the activity only twice [16]. the heterogeneous catalytic ethylbenzene oxidation proceeds more slowly than homogeneous. localization of a free radical reaction inside micro pores seems to give rise to particular selectivity. Molecular isolation and the absence of intermolecular interactions (as revealed by EPR spectroscopy).10tetraazocyclododecane. The products yields are limited by the stability/activity ratio of iron porphyrin and these. mainly zeolite Y [16]. Thus. in general.54-nm diameter). cyclohexanol and cyclohexanone account for ~ 60% of the oxidation products. are dependent mainly on catalyst loading and microenvironment provided by support. But desorption of initial products such as cyclohexylperoxide or cyclohexanone is slow. the small amounts of o.and tetraaza macrocyclic ligands such as 1. the catalytic activity is practically unchanged if supported metal complex is used. are most frequently used [16].10-tetraazocyclododecane. 1. such as side-on peroxide. The creation of mesopores in zeolite particles to increase accessibility to the internal surface has been the subject of many studies (mesopore-modified zeolites). 0. methylphenylcarbinole. while it is suppressed significantly in the case of the encapsulated complexes.7.7. cyclohexane is easily adsorbed in the micro pores [18]. In contrast. The differences in selectivity are attributed to the formation of different types of “active” copper–oxygen intermediates. Consequently. containing super cages. In the case of the reaction of cyclohexane oxidation to adipic acid with air in the presence of Fe –aluminophosphate-31 (ALPO-31) (with narrow pore. faujasites. as a result of low silicon to aluminum ration. Even with dealumination of the structure up to a silicon to aluminum ratio above 100.4.4. Acetophenone was the major product. as analogous homogeneous catalyst. FeTF8PP.and p-hydroxyacetophenones were also formed.7. μ-1. in different proportions over the “neat” and encapsulated complexes (A−C species): .2-peroxo. and 1.8.7-triazocyclononane. synergism due to interaction with the zeolite framework and restricted access of the active site to ethylbenzene are the probable reasons for the differences in activity/selectivity of the encapsulated catalysts. The deactivation by sorption of polar products and solventы on pores of zeolite still remained a serious issue for oxidation of alkanes (with low polarity). Thermal decay of this peroxo complex in the presence of toluene or ethylbenzene leads to rarely seen C-H activation chemistry. aided by H2. Larisa A. was bonded to sites where acidic silanol groups had been presented [24]. coincide with results. It was established that in the presence of ethylene and H2 surface-bound catalytic active mononuclear cationic Ru(acac)(C2H4)22+ complex entered into a catalytic cycle for ethylene dimerization.2-peroxodicopper(II) complex [{°LCuII}2(O22-)]2+ forms from the reaction of the mononuclear compound [CuI(°L)(MeCN)]B(C6F5)4 (°LCuI) with O2 in no coordinating solvents at -80°C. which are received with the cationic metalloporphyrins in solution. C−C bond formation. the ration c-one/c-ol is higher than in the use of supported on silica and polystyrene catalysts and. Water soluble catalysts combining the properties of metal complexes and surfactants on the basis of terminally functionalized polyethylene glycols (PEG) and block-copolymers of ethylene oxide and propylene oxide with various combinations of ethylene and propylene oxide fragments were investigated [22]. respectively. were used as ligands for preparation Co(II) complexes. Fe) and supported catalysts (silica. Such surrounding is labile and does not preclude from activation of dioxygen. The activity of the liquid-phase polyhalogenated metalloporphyrins (Co. including oxidation. In the last case. Polymers. Zaikov It [21] is established that with an anisole-containing polypyridylamine. Mononuclear ruthenium complexes are catalysts for numerous reactions in solution. The cationic Ru(acac)(C2H4)22+ complex. .466 Ludmila I. are formed. The only product was acetophenone. Very similar toluene oxygenation chemistry occurs with dicopper(III)-bis-μ-oxo species [{BzLCuIII}2(μ-O2-)2]2+ [see Chapter VII]. Cobalt remains fixed at the end of the polymer chain with acac-ligand and is surrounded by oxygen atoms of the PEG chain. [23]. Dealuminated zeolite Y was used as a crystalline support for a mononuclear ruthenium complex synthesized from cis-Ru(acac)2(C2H4)2. Macro complexes PEG-acacCo turned out to be more active than their non-polymeric analogues in oxidation of ethylbenzene by dioxygen under the same temperature (120°C). Mosolova and Gennady E. benzaldehyde and acetophenone/ 1-phenylethanol mixture (~1:1). potential ligand °L. Mn. functionalized by dipyridyl and acetyl acetone. in fact. Matienko. formed as result of the dissociation of half of the acac ligands from the ruthenium. and activation of CO2 and C−H bonds. a μ-1. polystyrene) and the cationic metalloporphyrins encapsulated in NaX zeolite are founded to be active for cyclooctane oxidation with molecular O2 into ketone and alcohol with primary ketone formation. Ligands L2 control transformation of Ni(L1)2 complexes into more active selective particles (catalyst K2). In that. DMF.and hetero-poly nuclear heteroligand complexes of general composition Nix(acac)y(L1ox)z(L2)n (L1ox= MeCOO-) (K2. In that the catalytic activity of the in situ formed in situ primary complexes M(L1)2·L2 (catalyst K1). the rise in SPEH is reached at the expense of catalyst participation in activation reaction of O2. and increase in initial oxidation rate (I macro stage) [60.61]. as result of controlled by L2 ligand regioselective addition of O2 to nucleophilic carbon γ-atom of one of the ligands L1.max ≈ 90%) in comparison with I macro stage. acetaldehyde. At the III macro stage. but also the selectivity (S = [PEH] / Δ[RH]·100%) and conversion degree (C = Δ[RH] / [RH]0·100%) of alkylarens (ethylbenzene. MP. selective catalyst K2 (II macro stage) is formed. cumene) oxidation to the corresponding hydroperoxides by molecular O2 upon addition of electron-donating monodentate ligands L2 (L2 = HMPA (hexamethylphosphorus triamide). K1 ⎯→ K2 ⎯→ K3 We have established that in the case of use of nickel complexes Ni(L1)2 (L1=acac¯). In this connection at the first macro stage. containing ligands L2 in axial position is higher than that of original complexes Ni(L1)2. and elimination of CO (Scheme 1-3) [29. the sharp fall of the SPEH is associated with heterolysis of PEH to phenol and acetaldehyde. N-methyl pyrrolidone-2 (MP)). are observed (II macro stage). accompanied by proton transfer and bonds redistribution in formed transition complex leads to break of cycle configuration with formation of (OAc-) ligand. and inhibition of chain and heterolytic decomposition of PEH. As a result of this process.31]. L1=acac-) was discovered by authors of the articles [25-27]. reactive mono. MSt (M = Li. acetophenone (AP) and methylphenylcarbinol. The coordination of exo ligand L2 to an M(L1)2 changes symmetry of complex and its oxidative-reductive activity. Fe(III). MODIFICATION OF METALLOCOMPLEX CATALYSTS BY ADDITION OF MONODENTATE AXIAL LIGANDS The phenomenon of a substantial rise of not only initial rate (w0). which is manifested in the acceleration of free radical formation in the steps of chain initiation (activation by O2) and homolytic decomposition of α-phenyl ethyl hydroperoxide (PEH). the selectivity of ethylbenzene oxidation into PEH is not high (SPEH. MSt) in the process of ethylbenzene oxidation (120°C) was elucidated [28-31]. Transformation of complexes .Methods for Enhancing the Activity and Selectivity… 467 III. Besides this.max = 80%). With process development. Co(II).2. Coordination of electron-donor exo ligand L2 with Ni(L1)2 stabilized the intermediate zwitter-ion L2(L1M(L1)+O2¯) and increased the probability of regio-selective insertion of O2 to acetylacetonate ligand activated by coordination with nickel(II) ion. "А") are formed. catalyzed by the completely transformed catalyst (catalyst K3) [29-31]. the increase in SPEH (SPEH. Na. dimethyl formamide (DMF). is changed from consequent (under hydroperoxide decomposition) to parallel at the expense of modified catalyst in the chain propagation (Cat + RO2•→). K) to transition metal complexes М(L1)n (M = Ni(II). the direction of formation of side products. The further incorporation of O2 into chelate cycle. and decrease in reaction w. (MPC). The mechanism of control of M(L1)2 complexes catalytic activity by adding electrondonating monodentate ligands L2 (L2 = HMPA. Scheme III. Scheme III. initiated with exo ligand L2. The structure of the complex "A" with L2 =MP (HMPA) was confirmed kinetically and using various physicochemical methods of analysis (mass-spectrometry. Li. namely. ARD [34] and its models [35].2. MSt)) leads to formation of homo bi.2. Ni(acac)2·L2 (L2 = HMPA. chelate group (O/NH)) is realized in the absence of activating ligands (L2) [30] (L1ox=NHCOMe.(L2 = HMPA. MP. Cu(II). 33].31]. Matienko.2. K) heteroligand complexes K2 ("А"): Ni2(OAc)3(acac)L2 (Scheme 1) [29.or MeCOO-) (Scheme 2) by analogy with reactions of oxygenation imitating the action of L-tryptophan-2. DMF. Transformation of Ni(L1)2 (L1=enamac-.and . and element analysis). Scheme III. Larisa A.3.2.3-dioxygenase [32. This applies to the functional enzyme models.1. DMF. The principle scheme of oxygenation of ligand (acac)¯ in complex with Ni(II). M=Na.468 Ludmila I. Zaikov K1. Mosolova and Gennady E. electron and IR-spectroscopy. MP) or hetero-three nuclear (L2 = MSt. Similar change in complexes' ligand environment as a consequence of acetylacetonate ligand oxidative cleavage under the action of O2 was observed in --reactions catalyzed of the only known-to-date a Ni(II)-containing dioxygenase – acireductone dioxygenase. In this case.and outer-sphere (hydrogen bonding) coordination of DMF ligand to Fe(II)(acac)2 may promote the acetylacetonate ligand oxygenation by another route realized in the action of Fe(II) acetylacetone dioxygenase (Dke 1). into more reactive selective catalytic species could also be a result of ligand L2controlled regioselective addition of O2 to the γ-C atom of acetylacetonate ligand [38]. oxygen adds to C−C bond (rather than inserts into the C=C bond as in the catalysis with nickel(II) complexes with consequent breakdown of cycle configuration through Criegee mechanism) to afford intermediate “B”. [36. The similarity of kinetic dependences in the parent processes of ethylbenzene oxidation in the presence of {Fe(III)(acac)3+L2} (L2=DMF) and {Ni(II) (acac)2+L2} (L2=DMF.2-dioxetane fragment.. HMPA) (120°C) make it possible to assume that transformation of in situ formed Fe(II)(acac)2·DMF complexes. The process is completed with the formation of the (OAc)⎯ chelate ligand and methylglyoxal as the second decomposition product of a modified acac-ring (Scheme 4) [39]. . i. which catalyze the decomposition of βdiketones in the enol form to carbonyl compounds with CO evolution. the favorable combination of the electronic and steric factors that operate during the inner.3-dioxygenases. an Fe complex with a chelate ligand containing 1.Methods for Enhancing the Activity and Selectivity… 469 Fe(II)-containing quercetin 2. However. 37].e. 470 Ludmila I. It is the formation of the completely oxidized form of Fe(OAc)2 catalyst that is responsible for the sharp drop of selectivity SPEH in the third macro stage [26. We established that the mechanism of the ethylbenzene oxidation (1200C).4. 29. Larisa A. AP and .2. The MPC becomes the major product of oxidation. SMPC. Zaikov Scheme III. Matienko. which (as and Ni(OAc)2) catalyze heterolytic decomposition of PEH to phenol and acetaldehyde (Scheme 4). catalyzed Fe(III)(acac)3 in the absence of the activating ligand L2 at rather high value of [Cat] (>5·10-3 mole/l) is changed.0 ≈ 50%. 38]. As in the case of catalysis by Ni complexes in the ethylbenzene oxidation.38]. The final product of the Fe(II)(acac)2 conversion is the complex Fe(OAc)2. catalyzed by Fe(II)(acac)2·L2 complexes. Mosolova and Gennady E. the reactive selective transformation products are polynuclear hetero ligand complexes with the hypothetical structure: Fe(II)x(acac)y(OAc)z(L2)n (L2=DMF) [26. The principle scheme of dioxygen-dependent conversion of 2.4-pentandione catalyzed by acetyl acetone dioxygenase Fe(II). The radical Q. and releasing at the oxygenation of Ni(L1)2·L2 (Scheme 1-3). was sufficiently high: SPEH. Introduction of Activating Additives in the Course of Catalyzed Oxidation Process The formation of the active catalyst in the second macro stage of ethylbenzene oxidation catalyzed by the {Ni(II)(acac)2+L2} system was proved by us from the effect of the introduction of a fresh portion of Ni(II)(acac)2 complex in the stage of a well-developed process [33]. . the method of catalytic system activation in developed oxidation process was used [8]. is produced at the maximal rate from the very beginning of the reaction. catalyzed by Ni(L1)2 (1. but AP is the product of MPC oxidation. including the in situ formation of the prime complexes Ni(L1)2·L2 and following the Ni(L1)2·L2 oxygenation to more active selective catalysts. one of the products of (acac)¯ . did not exceed C = 2-4% [29. The transformation of the nascent Q(L1)2)Fe(II) complexes into more active selective catalyst of the hypothetical structure Fe(II)x(acac)y(OAc)z(Q)n during the Fe(III)(acac)3 – catalyzed ethylbenzene oxidation most likely follows the described above mechanism (Scheme 4).max not less than 90%.max = 90%. catalyzed by Ni(L1)2 (1. It was established by us earlier that at the relatively low nickel catalyst concentration in the absence of L2. allow the solution to the problem of improving of catalyst of the selective oxidation. The established mechanism of catalysis of the system {Ni(L1)2+L2}. catalyzed with the only known-to-date an Ni(II)-containing dioxygenase-acireductone dioxygenase.max is not accompanied the growth in the conversion C. which was used in our researches (see below). The transformation of Fe(III)(acac)3 into new catalytically active species. and the mechanisms by which this particular cleavage is achieved are surprisingly diverse [42].Methods for Enhancing the Activity and Selectivity… 471 MPC are produced not parallel. For an increase of conversion degree of oxidation at maintaining of SPEH. 29]. The enzymatic cleavage of C-C bonds in β-diketones has growing significance for various aspects of bioremediation. The change of the catalysis mechanism may be due to variation in the reactivity of iron complexes. But the growth in SPEH. as acetophenone and methyl phenyl carbinol and PEH. A method of affecting a chemical reaction not only in its initial stages but also in subsequent stages of the fully developed process is an effective way of optimizing complex multi-stage oxidation processes [8. the selectivity of the ethylbenzene oxidation into PEH. is stable and inactive as an initiator of free-radical oxidation reactions [38]: It was shown by us that this transformation is negligible in the concentration range of [Cat] ≤ 5·10-3 mole/l. ranging from metal-assisted hydrolytic processes [42] to those catalyzed by dioxygenases [41]. is now considered a candidate for a new class of neural messengers [41]. Fe(II)(acac)2–Q.5·10-4 mol/l). Carbon monoxide. biocatalysis. The value C into PEH in the ethylbenzene oxidation.30]. previously considered biologically relevant only as a toxic waste product.ligand oxygenate breakdown path. ARD. and mammalian physiology. is proposed. Phenol. presumably. which can result from the oxidation of the ligand (acac)¯ with Fe(III) ion.5·10-4 mol/l). 2.0·10-3 mol/l)} catalytic system the maximum possible conversion degree C.5·10-4 mol/l. Mosolova and Gennady E. Larisa A. Zaikov In the case of introduction of Ni(II)(acac)2 into ethylbenzene. A prerequisite for the catalyst reactivation is introduction of additives at the instant the reaction reaches its steady-state mode with respect to SPEH (SPEH = SPEH.0·10-3 mol/l.472 Ludmila I. [Ni(II)(acac)2]0=1. The second step is the regioselective oxygenation of the latter to form a binuclear Ni2(acac)(OAc)3·L2 complex ("А"). [HMPA]=1.max). If additional amounts of catalyst were added in the moments corresponding to decrease in oxidation selectivity (SPEH < SPEH. Mechanism of activation consists in increase of steady-state concentration of catalytically active complex "A" (see Scheme 1) responsible for selectivity of oxidation process. . no reactivation of catalytic system occurred. Figure III. Matienko.5·10-4 mol/l)+HMPA(1. Dependences of selectivity of ethylbenzene oxidation into PEH (SPEH) on conversion level of ethylbenzene (CPEH) in the presence of system {{Ni(II)(acac)2 +HMPA} without admixtures (1) and with 4. 29]. The fast exchange interaction of the primary complex Ni(acac)2·L2 with Ni(OAc)2 complex was formed during the ethylbenzene oxidation to afford a heteroligand complex Ni(acac)(OAc)·L2: Ni(II)(acac)2·L2 + Ni(II)(OAc)2 ⎯→ Ni(II)(acac)(OAc)·L2 (1) 2. 120°С. Activation proceeds in two stages: 1.1. at which reaction selectivity is not less than SPEH = 90% is significantly increased (by a factor of ∼ 3) (Figure 1) [8.5·10-4 mol/l Ni(II)(acac)2 (2) added in the course of the oxidation. oxidation reaction catalyzed by {Ni(II)(acac)2(1.max at C < 4% and C > 5-6%). which was attributed to the oxidation of uncoordinated acetylacetone acacH [8]. . In that. catalyzed by {Co(II)(acac)2+ HMPA} system) unlike the results.3). the degree of conversion CS=90% increased to the lesser extent as compared with the addition of Ni(acac)2 to this system. in the formation of a binuclear nickel complex.29]. MODELING OF TRANSITION METAL COMPLEX CATALYSTS UPON ADDITION OF AMMONIUM QUATERNARY SALTS AND MACROCYCLE POLYETHERS AS LIGANDS-MODIFIERS. 2. received at the ethylbenzene oxidation. π-acceptors TCE and CA electrophylicaly attack acetylacetonate ligand by γ-С-atom stronger than O2 forming outspherical complexes and thus preventing the O2 addition by this bond and the formation of a reactive binuclear heteroligand complex. amphiphilic molecules of these salts aggregate to micelles and at higher concentrations to lyotropic (typical member is CTAB.2). The passivation of catalytic system upon the introduction of TCE or CA can be rationalized as follows: since electron affinity is increased in the raw О2(0. the conversion CS=90% increases from 5 to 9%.6. the increase in CS=90% occurs.3.Methods for Enhancing the Activity and Selectivity… Ni(II)(acac)(OAc)·L2 + O2 ⎯→ Ni2(acac)(OAc)3·L2 (2) 473 Activation of catalytic system {Ni(II)(acac)2+L2} by acacH additives testifies to favor of exchange interaction between Ni(II)(acac)2·L2 and Ni(II)(OAc)2 (1).3) < TCE(1. The increase in CS=90% does not take place in the case of the introduction of a fresh portion Co(II)(acac)2 in the ethylbenzene oxidation.III. Besides this. The possible mechanism includes the reaction of Co(II)(acac)2·L2 with peroxide radicals with formation of catalytically active complexes of the probable structure [Co(III)(L1)2·L2·(RO2¯)] [8] (see below. catalyzed by Co(II)(acac)2 without additives. catalyzed by {Ni(II)(acac)2+L2}. Chap. III. The role of the second stage (2) in catalyst activation. We have found [29] that the simultaneous addition of a fresh portion of Ni(II)(acac)2 and also a π-acceptor E (tetracyanethylene (TCE) or chloranil (CA)) into {Ni(II)(acac)2+L2} catalytic system did not increase the degree of conversion CS=90%. At the introduction of a fresh portion of Co(II)(acac)2 to the ethylbenzene oxidation. namely. In aqueous solution. The outer-sphere reaction of connection of E to γ-C atom of acetylacetonate ligand is followed by the formation of L2Ni(II)(acac)2•E [8. cetyltimethylammonium bromide) (or thermotropic) mesophases. quaternary ammonium salts are used as phase-transfer catalysts and as ionic liquids (ILs) in the synthesis of nanosized catalysts [42-46]. THE ROLE OF HYDROGEN-BONDING INTERACTIONS Quaternary ammonium salts are well-known as cationic surfactants. in this case. These results seems to be due to the another mechanism of transformation of the primary complexes Co(II)(acac)2·L2 to more reactive selective catalyst.87) <CА(1. was proved by introducing electron-withdrawing additives. The appearance of new absorption in the electronic spectra of the mixtures {Ni(II)(acac)2+MP+E} as compared with the spectra of E and {Ni(II)(acac)2+MP} testify to the complexes with charge transfer CTC L2Ni(II)(acac)2•E favor. However. 48]. Crown ethers are also of interest in biologically modeling of enzyme catalysis and as phase transfer catalysts [43. moreover. it forms R4NBr(Br2)n or R4NBr(HBr)n adducts. . Thus. thus activating Br2 or salts of HBr for electrophilic attack on the aromatic ring [44]. Cofactor of oxidation-reduction enzyme methyl-S-coenzyme-M-reductase in structure of methanogene bacteria is tetra-azamacrocycle nickel complex with hydrocorfine Ni(I)F430 axially coordinated inside of enzyme cavity. The latter is the already mentioned Ni(II)containing dioxygenase ARD [34]. in various catalytic reactions that occur in water. [NiFe]-hydrogenase.474 Ludmila I. for example. Superoxide dismutase contains a catalytic cycle Ni(II) ⇔ Ni(III). These salts can act as catalysts of phase transfer. At the same time. Cu) form with R4NX (X=(acac)-. in reactions of the oxobromination of aromatic compounds a lipophylic ammonium salt transfers H2O2 into the organic phase. Mosolova and Gennady E. In the catalytic oxidation of styrene to benzaldehyde by H2O2 in water-organic solvent systems ammonium salts completely transfer H2O2 and catalyst (Ru. In the oxidation of p-xylene in a water-organic system in the presence of CoBr2 and R4NBr. the other ligand and also the solvent [54]. Matienko. since it is a Lewis acid. the incorporation of transition metals into the cavities of macrocycle polyether was confirmed by different physicochemical methods. It is established that active sites of urease are binuclear nickel complexes containing N/O-donor ligands. the polyether. Larisa A. quaternary ammonium salts R4NX can play two different roles. Interest in the study of structure and catalytic activity of nickel complexes (especially nickel complexes with macrocycle ligands) has increased recently in connection with the discovery of nickel-containing enzymes [52-53]. The ability of the quaternary ammonium salts as well as macrocycle polyethers to form complexes with transition metals compounds was used by us in designing new effective catalytic systems for ethylbenzene oxidation to α-phenylethy hydroperoxide. but also by the whole ensemble of electron and spatial factors induced by the metal atom. It was proved. Spectral proofs of octahedral geometry for these complexes were obtained [49]. Complexes Me4NiBr3 were synthesized and their physical properties were studied [50]. To date. It is known also that the catalytic activity of CTAB in the ROOH decomposition in the presence of metals compounds is dependent on structural changes in the formed inverse micelles [47. the complex formation affects the properties of the catalyst by the changing of its activity (rate and selectivity of the reaction) [45]. Zaikov As was shown earlier. The selective complexation ability of crown ethers is among their most attractive properties. the specific structure of resulting complexes is determined not only by the geometric compatibility between the metal atom and the crown-ether cavity. that М(acac)2 (M=Ni.organic medium. Moreover. Intermolecular and intramolecular hydrogen bonds and other noncovalent interactions are specific in molecular recognition [51]. 51]. the catalytically active species are complexes CoBr2 with R4NBr [46]. The ability of quaternary ammonium salts to complex formation with transition metals compounds was established. R=Me) complexes of [R4N][М(acac)3] structure. Pd) into the organic phase by forming hydrogen bonds. for example. with an Ni(III) complex in active site. but also R4NX salts are often directly involved in catalytic reaction itself. max ≥ 90%. including participation of catalyst (Cat=M) in chain initiation under catalyst interaction with ROOH (1’) and under interaction RH with O2 (1’’. the rate of reaction should be decreased. in chain propagation (Cat + RO2•→) (2’) and assuming the chain decomposition of ROOH (4) and quadratic chain termination reaction (5) (Scheme III.Methods for Enhancing the Activity and Selectivity… 475 Catalysis by Ni(L1)2 in the Presence of Ligand-modifiers L2 It was established by us earlier that the selectivity of the ethylbenzene oxidation into PEH. Mn+ + O2 → Mn+.3.8].5·10-4 mol/l). was sufficiently high: SPEH. Scheme III.1). catalyzed by Ni(L1)2 at the relatively low nickel catalyst concentrations (≤1. 2 RO2• → products RO2• + M → products [ROOH]max = (4) (4’) (5) (5’) k2k2''[RH] k4 (k2'[M ] + k2''[RH]) k3[M ] 2k4k5 (k2[RH] + k2'[M ]) 2 wmax = k22 [RH]2= . (1) (1’) (1’’) (2) (2’) (2’’) (3) ROOH + RO2• → products + (R’)• ROOH + M(n+1)+ → Mn+ + RO2• + H+. The precipitation Cat in the chain propagation (2’) makes it possible to explain the dependence of [ROOH]max and the maximal rate on catalyst concentration..O2 RH→ M(n+1)++ R• + HO2• ROOH → RO• + •OH RH + O2 → R• + • HO2• R• + O2 → RO2•RH→ ROOH + R• RO2• + M → products + (R’)• RH + (R’)• → R• + R’H ROOH +Mn+ → M(n+1)++ OH¯ + RO• RH→ → ROOH + R• + M(n+1)+. and [ROOH]max should be increased with decrease in [Cat]0 [3. In this case. This fact may be expected from the analysis of the scheme of catalyzed oxidation. 2)..3.1. 5·10-4 mol/l).max not less than 90%. Coordination of 18C6 or R4NX with Ni(II)(acac)2 seemed to promote oxidative transformation of nickel (II) complexes (schemes 1–3) into catalytically active particles and result in increase in C at conservation of SPEH. Matienko. catalyzed by Ni(L1)2 (1. Our assumption was confirmed. the addition of 18C6 substantially increases the initial rate w0 of reaction is (Figure 1). was not exceeded C = 2-4% [61. 55]. A really significant increase in conversion degree of oxidation into PEH at maintenance of selectivity on level SPEH ~ 90% occurs. Products AP and MPC are formed not from PEH but parallel with PEH. 57]. the extraordinary results were received in the case of the introduction of 18C6 or Me4NBr additives into ethylbenzene oxidation catalyzed by complexes Ni(L1)2. the direction of byproducts formation changed.max=95% is higher than under catalysis by Ni(II)(acac)2 without addition of L2. As one can see early.e. appearing under coordination of 18C6 or R4NX. Mosolova and Gennady E. the effective method for increase in parameter C at the conservation of SPEH. 55]. and furthermore wAP / wMPC ≠ 0 at t→0. may not only accelerate the active multi-ligand complex formation (Schemes 1-4) but also hinder the transformation of active catalyst into inactive particles. In that. Furthermore.max also increased. In that. The controlled by R4NX regio-selective connection of O2 by γ-C-atom of (acac)¯ ligand in complex М(acac)n·R4NX is probable enough. At these conditions. Co(II))). the growth in SPEH. As mentioned before. 56. Zaikov Really. as it occurs at the case of complexes with 18C6. Larisa A. that indicates on parallelism of formation of AP and MPC (P = AP or MPC) [8].max not less than 90% in the ethylbenzene oxidation.max increases from 90% to 98-99% [8. catalyzed by {Ni(L1)2 (1. the addition of electron-donor monodentate ligands turned out to be low effective [8. The SPEH. the favorable combination of H-bonding and steric factors. For example.max is not accompanied with the increase in the conversion C.O)2 chelate unit) with 18C6 (1:1 and 1:2) and from 12 up to 16% for complex of Ni(II)(enamac)2 (Ni(O. The maximum selectivity of ethylbenzene oxidation SPEH. the value of SPEH. The value C into PEH in the ethylbenzene oxidation. practically was not observed.476 Ludmila I. Our assumption was based on the next literature data.62]. the value SPEH. SPEH exceeded 90%. MP) into system. moreover. i. the ability of crown-ethers to catalyze electrophilic reactions of connection to γ-C-atom of acac--ligand is known [43. is the introduction of activated additives of Ni(II)(acac)2 into developed reaction. 25. We established that in this case. 29] and the change of SPEH. Obviously. wP / wPEH ≠ 0 at t→0.5·10-4 mol/l (M=Ni(II). In the case of additives of Me4NBr into reaction of ethylbenzene oxidation catalyzed by Ni(II)(acac)2. The degree of conversion into PEH is increased from 4-6 up to 12% for complexes of Ni(II)(acac)2 (Ni(O. Various electrophilic reactions in complexes R4N+(X…HOCMe=CHCOMe)¯ proceed by γ-C-atom of acetylacetone [43.5·10-4 mol/l) + L2}.NH)2 chelate unit) with 18C6 (1:1). but at C=2-3%.max and CS=90% under the introduction of additives L2 (L2 = HMPA.max is reached not at the beginning of reaction of ethylbenzene oxidation. It is known that R4NX in hydrocarbon mediums forms with acetylacetone complexes with strong hydrogen bond R4N+(X…HOCMe=CHCOMe)¯ in which acetylacetone is totally enolyzed [55]. we observed the decrease in the rate of reaction and the growth in [ROOH]max with the decrease in [Cat]0 (in the case of M(II)(L1)2] ≤ 1. . 0)2 Ni(O. However.25 5. AP and MPC were established to be formed parallel (wP/wPEH ≠ 0 at t→0) in the course of the process. The initial rate of PEH accumulation wPEH.3.38 2.Methods for Enhancing the Activity and Selectivity… 477 Selectivity remains in the limits 90% <S≤ 95% to deeper transformation degrees of ethylbenzene C≈19% than in the presence of additives 18C6 (C≈12%) [8.64 8. Additives of 18C6 or Me4NBr to ethylbenzene oxidation reaction catalyzed by Ni(L1)2 lead to significant hindering of heterolysis of PEH to afford phenol (PhOH).61 6. The products PEH.5·10-4 mol/l. 120°С.0 is higher than in the case of ethylbenzene oxidation catalyzed by the system {Ni(II)(acac)2 + Me4NBr}.59].max decrease from 95 to 80-82% [58.36 0 0 0 0 9. However.NH)2 14 12 10 8 6 4 2 0 12. The decrease in PEH selectivity connected with heterolysis of PEH. The latter reaction is responsible for the selectivity reduction in the fully developed process. in the substitution of an n-C16H33 radical for one of methyl radicals in Me4NBr (if cetyltimethylammonium bromide (CTAB) is added) SPEH. initial rates of accumulation of side products of reaction of AP with MPC are also significantly increased (Figure 3).15 4.44 Figure III. in ∼ 4 times in comparison with catalysis of ethylbenzene oxidation by Ni(II)(acac)2 complex. 96].1. Influence of quaternary ammonium salt on catalytic activity of Ni(II)(acac)2 as selective catalyst of ethylbenzene oxidation into PEH extremely depends on the structure of radical R in ammonium cation. AP and MPC were formed also parallel (wAP/wMPC≠0 at t→0).10 5 . induction period of PhOH formation in the presence of Me4NBr additives considerably exceeded that of the case of 18C6 [56-59]. Ni(O. wo. In that. 95. L1=acac-1. Dependences of initial rates w0 (mol l-1 s-1) on [18К6] concentration (mol/l) in ethylbenzene oxidation reactions catalyzed by {M(L1)2+18К6} (M=Ni(II). Analysis of consequence of ethylbenzene oxidation products’ formation catalyzed by systems {Ni(L1)2+18C6} and {Ni(II)(acac)2+R4NBr} showed that the mechanism of products formation is unchanged as compared with oxidations catalyzed by Ni(L1)2 or {Ni(L1)2+HMPA}. enamac-1). [M(L1)2]=1. The phenol formation is observed in lower conversions of RH transformation. Thus. the initial reaction rate w0 is significantly increased.65 8. 10 6 .2 2 1.6 1. enamac-1) on [R4NBr] (mol/l). II-wAP+MPC. As regards the parameter S·C (S·C ~ 24·102 (%.7 17 61 27 15 2. IV-wAP+MPC 70 60 50 40 30 20 10 0 000 0 27 21 11 2. L1=acac-1.3. [M(L1)2]=1. as a rule. w.0.%)) the system {Ni(II)(acac)2+Me4NBr} proved to be the most active in ethylbenzene oxidation into PEH as compared with systems {Ni(II)(L1)2+18C6(HMPA)} [57]. Larisa A.2.5·10-4 mol/l. S0 ≤ S ≤ Slim (Smax = 80%) (Co) [8. Mosolova and Gennady E. insignificant at T ≥ 1200. For comparable by value systems selectivity as Slim the value Slim = 80%. mol l -1 s-1 I row-wPEH.0. III-wPEH. Zaikov Catalysis of ethylbenzene oxidation initiated by {Ni(II)(acac)2 + CTAB} system is not apparently associated with formation of micro phase such as inverse micelles. because the micellar effect of CTAB manifested at T < 100° [80] is.1 2. which evaluated a change of S in the course of oxidation from S0 at the beginning of reaction to some Slim (Slim is an arbitrary value chosen as a standard). Co). as we saw the system {Ni(II)(acac)2 + CTAB} was not active in ROOH decomposition. For estimation of catalytic activity of nickel complexes as selective catalysts of ethylbenzene oxidation into α-phenylethylhydroperoxide. C − conversion at S = Slim.6 1.3 19 29 23 16. Matienko. we proposed to use parameter S·C.478 Ludmila I. . Dependences of initial rates w0 (mol l-1 s-1) and the rates w (mol l-1 s-1) in the ethylbenzene oxidations catalyzed by {M(L1)2+18К6} (M=Ni(II). The value selectivity was carried out in the limits S0 ≤ S ≥ Slim (Smax > 80%) (Ni. 120°С.8 1 2. w0 . approximately equal to selectivity of non-catalyzed ethylbenzene oxidation into PEH at initial stages of reaction. The S is mean value of selectivity of oxidation into PEH. Furthermore. was chosen.7 Figure III. 30]. [MP]=1·10-1.3 20. sy ystems {Ni(II)(a acac)2+L } with h L2=Me4NBr. 4. 1·10-3 (3).3. equal to 85% (18C6 6) or 95% (M Me NBr) at the beginning of f ethylbenzene e oxidation.Methods for Enhancin ng the Activity y and Selectivi ity… 479 30 25 20 15 10 5 0 L =0(HMP PA) Me4 NBr N 2 24 . 2 Fi igure III. without nicke el complex au uto-catalytic developing d of f process with h initial rates by order.3. 5.3.5 · 10 mol/l.6 18C6 Fi igure III. . The T PhOH fo ormation is ob bserved from th he very beginn ning of reactio on. lo ower was obse erved.4. . [N Ni(acac)2]=1·10 0-4. . {Ni(acac)2+MP}. P max 4 w sharply re was educed with the increase of ethylbenz zene conversi ion degree. [Ni(II)(acac) [ ]= =1.%) in the e ethylbenzene oxidation upon n catalysis by ca atalytic 2 -4 120°C. 18C6.3. {Ni(acac c)2+18C6}. We establi ished that in the t presence of 18C6 or R4NBr alone. Electron absorpti ion spectra of aqueous a solution ns: 1--Ni(acac) )2. [18C6]=2·10 0-4 (2). Hacac. The SPEH . 200C. 6 [H Hacac]=1. 2.9·10-6 mol/l.6 9 9. Pa arameter S·C·10 0-2 (%. 1 HMPА. 1:2 (L1= (acac)¯. 6 – Et3C6H5NC Cl (2. (ena amac)¯. = R4NB Br) ("А") for rmed in the course of ox xidation could d be due to the e formation of f both inter. 5 – -3 -3 0 Bu4NI (2. By th he parameter S·C = 15. Mat tienko. no fo ormation of 2 in ph henol (the pro oduct of hetero olysis of PEH H) was observed during firs st hours of oxi idation.3.9·10 02 (%. increases s considerably y at catalysis by b Ni(II)(enam mac)2 (Ni(O.6·10 mol/l). Larisa A. unlike ca atalysis by 2 N Ni(II)(acac) n the presence of the comple ex with the Ni i(O.3. 30].O)2 ch helate unit) (C =11%).2·10 ).3. points to the fo ormation of ac ctive complex xes Ni(L1)2 with w (L2) wi ith the follow wing composi ition 1:1 (L1= (acac)¯.48 80 Ludmila L I.3. The stability of polynuclear heteroligand complexes N x(L1)y(L1ox)z(L2)n (L1ox= MeCOO Ni M .4·10-3). 2 – 6 – -3 -3 {F Fe(III)(acac)3+R R4NBX}: 2 – Me M 4NBr (2. In th he absence of L2 selectivity y of the ethylb benzene oxida ation into PEH H not lower th han SPEH = 80 0%. L2=18C6. 20 C. Zaikov -5 Fi igure III. The more eff ficiency of N Ni(II)(enamac) a compared with w Ni(II)(aca ac)2 (w0. the fo ormation of su upramolecular structures is highly h probabl le [62-64]. 2) 2 [98].6 times s (Figure 2). 3 – ЦТАБ (2 2. Ni( (II)(enamac)2 can be compa ared to the Ni(II)(acac) N 2 co omplexes with 18C6 or Me M 4NBr (Figu ure III. In th his case.0·10 ). L2=18 8C6) and also o of their tran nsformation pr roducts (Figu ure 1(a.an nd intra-molec cular hydrogen n bonds. R4NB Br). Ta able III. .3·10 ). Besides thi is. (Spectra were record ded using R4NX X solutions as s a reference). It was esta ablished the influence i of the t chelate un nit on the act tivity of bicy yclic nickel 1 co omplexes Ni(L L )2 as selecti ive catalysts of o the ethylbe enzene oxidati ion into PEH [8. S·C) is most likely y due to the 2 as catalyst as el lectron-donating NH grou ups in the coordination unit of the nickel com mplex. 4 – Bu B 4NBr (2. Ab bsorption spectr ra of solutions (CHCl ( F 3) : 1 – Fe(III)(acac) 3 (2. The tr ransformation of the catalys st into more ac ctive selective e intermediate complexes (th he increase . b). .N NH)2 chelate unit) up to C=22% as com mpared to tha at for the oxi idation in the e presence of Ni(II)(acac)2 (Ni(O. Synergetic effects of increase in para ameter w0 and d S·C in the ethylbenzene oxidation.NH)2 chel late unit.1).5. Mosolova and Gennady y E. L2=18C6.%). ca atalyzed by sy ystems {Ni(L1)2+18C6} and d {Ni(II)(acac)2+R4NBr}.3·10 ). The T initial rat tes of the ox xidation is th he presence of o complex N Ni(II)(enamac) higher ~ in 2. the short-wave shift of the absorption band should be accompanied by a significant increase in the absorption of the solution at λ = 275 nm. the coordination of ligand L2=18C6 or R4NBr with metal ion proceeds with preservation of ligand L1 in internal coordination sphere of complex Ni(L1)2 [8. Evidently. too. can be caused by participation of the oxygen atoms of the acetylacetonate ion in the formation of coordination bonds with the ammonium ion or hydrogen bonds with alkyl substituents of the ammonium ion [58. ligands 18C6 and MP do not exhibit any absorption bands in region considered).3. (C2H5)4NBr. Such a change in the spectrum indicates the influence of R4NX coordinated in the outer sphere on conjugation in the ligand.2. as can be seen from Figure III.Methods for Enhancing the Activity and Selectivity… 481 in S·C).III. Scheme III. The possibility of outer sphere coordination of quaternary ammonium salts R4NX with βdiketonates (Ni(II). S· C = 19. Obviously. because otherwise.4. In the presence of 1 and 2. the presence of the (acac)¯− ligand in the coordinate sphere of Ni complex is one of the necessary conditions for the high catalytic activity of complexes Ni(L1)2·18C6n. when an aqueous solution of 18C6 is added to the Ni(acac)2 solution. and also products of their transformation: polynuclear heteroligand complexes Nix(L1)y(L1ox)z(18C6)n. occurs. A similar change in the intensity of the (acac)¯ absorption band is observed in the absorption spectra of Ni(acac)2 when it is coordinated with monodentate ligand MP (spectrum 4). For example.%) (2)) (Table III. 56-58]. when R4NX is coordinated in the outer coordination sphere of the metal. The change in the conjugation in the chelate ring of acetylacetonate complex. Under formation of complexes of Ni(acac)2 with R4NBr. Fe complex Fe(III)(acac)3 exhibit an intense absorption band at ν = 37·103 cm-1 (CHCl3) of the π – π* transition of the conjugated cycle of the acetylacetonate ion [95.0·10-2 (%. a decrease in absorption intensity of acetylacetonate ion (acac)¯ and a short-wave shift of the absorption maximum (spectra 1-3) take place (at that. The formation of complexes Ni(L1)2 with L2=18C6 or R4NBr was confirmed by UV spectra. in the absence of additives of activating axial ligand-modifiers L2 (Chap.1) [57]. a decrease in the intensity and a bathochromic shift of the absorption maximum to ν = 36·103 cm-1 (Δ λ ≈ 10 nm) are observed (Figure 4). (C2H5)3C6H5NCl and the other). Fe(III)) was demonstrated by us with UV spectrophotometry at the research of the absorption of Fe(III)(acac)3 solutions in the presence of solutions of various salts R4NX.596]. At that. In the UV edge of the spectrum. The transformation of 1 and 2 into the more active catalytic particles does not occur.3. For example. it was established that the absorption band of phenol associated with the π –π* transition experiences a bathochromic shift of 500 cm-1 due to formation of hydrogen bonds with dioxane[65] The complexes of the Ni salts with 18C6 and 15C5 (Ni(NO3)2•18C6•6H2O (1). CTAB. the autocatalytic development of the ethylbenzene oxidation is observed. 96]. 2NiCl2•15C6•6H2O (2) are more effective catalysts of the ethylbenzene oxidation into PEH in comparison with systems {Ni(L1)2·18C6n} (S·C = 16. . in this case. In the presence of salts R4NX (Me4NBr.%) (1). the formation of a complex between Ni(acac)2 and 18C6 does not lead to displacement of the acetylacetonate ligand from the inner coordination sphere of Ni(II).2). the outer sphere coordination of R4NBr (H– bonding) with acetylacetonate-ion is possible.6·10-2 (%. which correspond to the absorption maximum of acetylacetone (spectrum 5) [56]. in spite of axial coordination by the fifth coordination place of nickel (II) ion. 3. Parameter S·C in the ethylbenzene oxidation reactions catalyzed by nickel and cobalt complexes. conversion degree C from 5 up to 15% ([Cat] = 5·10-3 mol/l). These were the maximum effects of electron-donor monodentate ligands on the SPEH and C of ethylbenzene oxidation at catalysis by Fe(III)(acac)3 [38. Mosolova and Gennady E. at the catalysis by Fe(III)(acac)3 the SPEH. The effects of electron-donor exoligands-modifiers on parameters w.1. SPEH and C of the ethylbenzene oxidation catalyzed by Fe(III)(acac)3 were studied at [Cat] = 5·10-3 mol/l. They are formed parallel both at the beginning of reaction and at deeper stages of oxidation: wP/wPEH and wAP/wMPC is constant and nonzero at t → 0 (P=AP or MPC) [38. the dependence of [PEH]max on [Fe(III)(acac)3] shows an extremum. We also observed a reduction in the rate of ethylbenzene oxidation with the decrease of [Fe(III)(acac)3]. it was established that in ethylbenzene oxidation catalyzed by Fe(III)(acac)3 in concentration interval [Cat]=(0.59. Fe(III)(acac)3.2 9.482 Ludmila I. Matienko. Zaikov Table III. which is longer than that in catalysis by Fe(III)(acac)3.59].6 9. [Cat]=1.5÷5)·103 mol/l. After the acceleration period caused by the formation of Fe(II) complexes via chain initiation by the Fe(III) complexes (see Chapter VI). suggesting that the mechanism of catalysis is more complicated in this case [38. In this case. (80. 66]. wlim (HMPA) and the no . The no additive (synergistic) effects of growth in rate w0 (DMF).5·10-4 mol/l. Larisa A. the rate of the reaction under steady-state conditions is w = wmax = wlim (to ~ [PEH]max). However.59. Catalysis by Fe(III)(acac)3 in the Presence of Ligand-modifiers L2 As in the case of ethylbenzene oxidation catalyzed by nickel complexes (Ni(L1)2).0 19. are inactive in PEH decomposition [37.1 The higher values of parameter S·C for complex 2 as compared with 1 seems to be due to the specific feature of binuclear complex NiCl2 with 15C5. 120°С) the oxidation products MPC and AP as well as PEH are the major products. from SPEH = 42-46% to SPEH = 65%. [PEH] = [PEH]max.max increases as [Cat] is reduced. 65]. However. the Fe(II)−HMPA complexes do not undergo transformation into more active catalysts of ethylbenzene oxidation to hydroperoxide.58. and also due to the more stable bond of Ni – crown-ether for NiCl2. As shown above. in the course of oxidation.6 20. this increase is less significant. In our articles.9 15.9 21.8 14. and that may affect on the mechanism of catalysis. 1200C Cat Ni(enamac)2 {Ni(enamac)2+18К6} Ni(acac)2 {Ni(acac)2+18К6} Ni(NO3)2·18К6·6H2O(1) 2NiCl2·15К5·6H2O(2) {Co(acac)2+18К62} 2Co(NO3)2·18К6·6H2O(3) 2Co(NO3)2·15К6·6H2O(4) S·C·10-2(%. and formed in the course of ethylbenzene oxidation Fe(II)(acac)2.6 16. 66].%) 15. In the presence of electron-donor monodentate ligand HMPA SPEH.max is increased from 42 up to ~57% (80°С). which is reached in the developed process (Figure 9a (1. Additives of CTAB to ethylbenzene oxidation reaction catalyzed by Fe(III)(acac)3 lead to significant hindering of heterolysis of PEH with formation of phenol responsible for decrease in SPEH. in comparison with catalysis by Fe(III)(acac)3 (S· C=2. a value that approximately corresponds to the selectivity of ethylbenzene oxidation in the presence of ligand-free Fe(III)(acac)3 (5·10-3 mol/l) (80°С) under the steady-state reaction conditions. The conversion degree is increased from C = 4 up to ~ 8% (at SPEH=40-65%) (Figure 9a). and [PEH]max at catalysis by complexes (Fe(II)(acac)2)x·(R4NBr)y are observed. (С2H5)4NBr). Me4NBr). wAP/wMPC ≠ 0 at t → 0).36. DMF [38. C is {Fe(III)(acac)3+(C2H5 )4NBr} {Fe(III)(acac)3+CTAB } {Fe(III)(acac)3+Me4N Br} Fe(III)(acac)3 .59]. Then.3.97 2. the increase in SPEH occurs at the expense of significant decrease in AP and MPC formation rate in the process at parallel stages of chain propagation and chain quadratic termination (wP/wPEH ≠ 0 at t → 0. CTAB.6. Parameter S· C·10-2 (%. the SPEH.). as well as the complexes produced as a result of the transformation of Fe(II)(acac)2•L2 (L2 is DMF) during oxidation (Figure III.9 5. the increase in wPEH.%) in the ethylbenzene oxidation upon catalysis by Fe(III)(acac)3 and catalytic systems {Fe(III)(acac)3+R4NBr} with R4NBr=Me4NBr.1·102 (%. 2)).Methods for Enhancing the Activity and Selectivity… 483 monotonic character of the S·C (see below) dependence on [L2] at [Fe(III)(acac)3] = const seems to be due to the activity of the resulting Fe(II)(acac)2•L2 complexes.%)) (Figure III.7. (C2H5)4NBr. 2. respectively.1 Figure III. [Fe(III)(acac)3]=5·10-3 mol/l.4 times for R4NBr=CTAB. 80°C. for value Slim as standard. decrease in wP.5·10-3 mol/l. is higher than in the case of use of additives of monodentate ligands HMPA.46 2.3.5·10-3 mol/l)} (R4NBr=CTAB) (80°С). In a given case. The fast decrease in SPEH at the beginning steps of the process is connected with the transformation Fe(III) complexes in Fe(II) complexes in the course of ethylbenzene oxidation (the auto acceleration period of the reaction is observed).6). In ethylbenzene oxidation in the presence of {Fe(III)(acac)3(5·10-3 mol/l)+ R4NBr(0.0.3. 6 5 4 3 2 1 0 4. [R4NBr]=0. The growth in S·C is ∼ 2. we accept Slim =40%.max=65%. 1.0.6. the complexes Fe(II)x(acac)y(OAc)z(DMF)n. The no-additive (synergetic) effects of growth in S· C parameter and w0 observed in the reactions catalyzed by Fe(III)(acac)3 in the presence of R4NBr. the oxidative degradation of the acetylacetonate ligand may follow “dioxygenase-like” mechanism.484 Ludmila I. the addition of L2 has practically no effect on selectivity of ethylbenzene oxidation reaction. Dependences of selectivity (SPEH) of ethylbenzene oxidation reactions on the conversion (C) catalyzed by Fe(III)(acac)3 in the absence of additives L2(♦. Figure III. Zaikov the conversion for which SPEH ≤ Slim. forming in the process are not stable. Due to the favorable combination of the electronic and steric factors appeared at inner and outer sphere coordination (hydrogen bonding) of CTAB with Fe(II)(acac)2.1) and in the presence of L2= DMF(∆. There is a high probability of formation of stable complexes of structure Fe(II)x(acac)y(OAc)z(CTAB)n (“B”). described by Scheme 4.max (94%) in the presence of Me4NBr additives [38. 2) or L2=HMPA (□. produced as a result of the transformation of (Fe(II)(acac)2)x·(R4NBr)y during oxidation.3. 1200 C. [HMPA]=5·10-2 mol/l). As we saw at the catalysis by nickel complexes ιν the presence of the CTAB additives. though DMF like CTAB . In the absence of a catalyst. 3) ([DMF]=5·10-2 mol/l. Mosolova and Gennady E. Matienko. [Fe(III)(acac)3]=5·10-3 mol/l. Larisa A. the value of SPEH. In the case of catalysis by the {Fe(III)(acac)3 + DMF} system.max is reduced down from 90 to 80-82% as compared with increase in SPEH. and also obtained kinetic regularities of ethylbenzene oxidation indicate the formation catalytic active complexes [61] presumably of (Fe(II)(acac)2)x·(R4NBr)y as well as the complexes. Out-spherical coordination of CTAB evidently creates sterical hindrances for regio-selective oxidation of the (acac)¯− ligand and the transformation of the intermediate complex (“B”) into the final product of dioxygenation.7. and the reaction proceeds in the autocatalytic mode at w0 below that in the catalysis by Fe(III)(acac)3.59]. The most effect of increase in SC was obtained in the case of CTAB additives. Methods for Enhancing the Activity and Selectivity… 485 forms H-bonds with acetylacetonate ion [38]. since the probability of micelles formation obviously increases.max at the catalysis by the {Fe(III)(acac)3 + DMF} system was not higher in fact than SPEH. SPEH.7) [38]. Analogous mechanism of formation PEH. although HMPA as electron-donor ligand was characterized with a higher DN value (after V. the transformation of Fe(II)(acac)2)·HMPA was not observed. As we saw above. catalyzed by Fe(III)(acac)3(5·10-3 mol/l) in the presence of 18C6 additives (80°С).5·10-4 mol/l. as in the case of use of additives of ligands DMF or R4NBr.5·10-3 mol/l) and SPEH.5·10-3 mol/l. Thus.max at the catalysis by the {Fe(III)(acac)3 in the absence of the additives (Figure III. the dependence of SPEH оn С has extremum.3. Gutmann) as compared with DMF (Figure III. Catalysis of ethylbenzene oxidation initiated by {Fe(III)(acac)3 + CTAB} system (80°С) in the case of application of the small concentrations R4NBr (0. SPEH.max = 75. The rapid decrease in SPEH was observed. With the use of HMPA as exo ligand.7). we established the interesting fact—the catalytic effect of small concentrations of quaternary ammonium salts. wAP/wMPC ≠ 0 at t → 0. wP/wPEH ≠ 0 at t → 0. □ .3. At the [CTAB] concentration [CTAB] = 5·10-3 mol/l the rate of the PEH accumulation and [PEH]max decreases significantly. which in 10 times less than [Fe(III)(acac)3]. [R4NBr] = 0. AP and MPC is observed at the use of Me4NBr and (С2H5)4NBr additives. the system {Fe(III)(acac)3 + CTAB} was not active in decomposition of PEH.8. Figure III. It is known that salts QX can form complexes with metal compounds of variable composition. [Fe(III)(acac)3]=5·10-3 mol/l. which depends on the nature of solvent [59]. that did not form H – bonds with chelate ring of Fe(II)(acac)2. In reaction of the oxidation of ethylbenzene with dioxygen.max = 70% ([18C6]0 = 0.3. Δ – 18C6] = 5·10-3 mol/l. which do not form micelles.5·10-3 mol/l) is not connected with formation of micro-phase by the type of inverse or sphere micelles. The formation of poly nuclear heteroligand complexes (Fe(II)(acac)2)x·(R4NBr)y (and Fe(II)x(acac)y(OAc)z(R4NBr)n also seems to be probable. □). Dependence of SPEH от С in the reactions of the oxidation of ethylbenzene catalyzed by Fe(III)(acac)3 (♦) or catalytic systems {Fe(III)(acac)3+18C6} (Δ.7% ([18К6]0 = 5·10-3 mol/l) in the process . 800C. 89 5. 2:1) and structure dependent on type of crown-ether and solvent [53].58.1 [18C6]=0. [Fe(III)(acac)3]=5·10-3 mol/l.7 times at [18C6] = 5·10-4 mol/l.8 times at [18C6]0=0.9) [57.max = 65% in the case of use of CTAB as exo ligand-modifier [57. correspondingly.10-4 mol/l. is observed in comparison with catalysis by Fe(III)(acac)3 (S·C =2. presumably. there is a high probability of formation of sufficiently stable hetero ligand complexes of the common structure Fe(II)x(acac)y(OAc)z(18C6)n.%)) (Figure III.3. 5·10-3 mol/l.6 or 1.8). Larisa A. 5 times. 5. 1:2.9. The addition of 18C6 in the ethylbenzene oxidation with dioxygen catalyzed by Fe(III)(acac)3 results in the redistribution of the major oxidation products. Supposedly.486 Ludmila I. The significant increase in [PEH]max is observed ~ 1. Matienko. Zaikov are higher than SPEH. Obtained kinetic regularities of the oxidation of ethylbenzene testify to formation. accordingly.58. 5.1·102 (%.5 and 2.60].10-3 mol/l Figure III.3 2. Additives of 18C6 lead to significant hindering of heterolysis of PEH with of the formation of phenol. due to the favorable combination of the electronic and steric factors appeared at inner and outer sphere coordination (hydrogen bonding) of 18C6 with Fe(II)(acac)2 (as also in the case of catalysis with complexes with CTAB [96]). occurs. It is known that Fe(II) and Fe(III) halogens form complexes with crown-ethers of variable composition (1:1. responsible for decrease in selectivity. 800C.%) in the reactions of the oxidation of ethylbenzene catalyzed by Fe(III)(acac)3 or catalytic systems {Fe(III)(acac)3+18C6}. the intermediate products of the oxygenation of (acac)ligands in the (Fe(II)(acac)2)p·(18C6)q complexes by analogy to the catalysis by acetyl . of (Fe(II)(acac)2)p·(18C6)q complexes and products of their transformations in the course of oxidation. synergetic effect of increase in S·C parameter ~ 2.60] (Figure III.%) 7 6 5 4 3 2 1 0 5.5·10-3 mol/l and [18C6]0 = 5·10-3 mol/l. at that decrease in [AP] and [MPC] ~ 4. In the presence of catalytic system {Fe(III)(acac)3+18C6}.3. Mosolova and Gennady E.3. -2 S·C·10 (%. The values of parameter S·C·10-2 (%. catalyzed by Co(II)(acac)2 [94].0·10-3 mol/l.max at ratio [Co(II)(acac)2]/ [18C6]=1:2 ·insignificant exceeds value SPEH. At the concentrations [Ni(II)(acac)2]0 > 1. 57].0)·10-3 mol/l).30]. There was an interesting fact established.5·10-4 mol/l the use of L2 (HMPA) additives results in the high SPEH. The additives 18C6 cause significant increase in SPEH. The PEH heterolysis with the PhOH formation seems to be due the decrease in Co(II)/Co(III) ratio with the decrease in catalyst concentration [1. The extreme dependence of SPEH on C at the small of [Co(II)(acac)2]=(0.max in the ethylbenzene oxidation catalyzed by coordinated saturated complexes Co(II)(acac)2·2HMPA [33. in the absence of ligand-modifiers L2 the ethylbenzene oxidation.9·10-2 (%. 1:2) [53. the selectivity of the catalytic ethylbenzene oxidation into PEH was sufficiently high: SPEH.5·10-4 mol/l)+18C6(3.max =80-85% and C = 10-14% of the ethylbenzene oxidation. The dependence of SPEH on C has extremum at the more values [Cat]0 ≥ 1.11. Synergetic effects of increase in parameter w0 (the maximum on the dependence w0 against [18C6]) is due to the formation of complexes with different ratio Co(acac)2:18К6 (2:1. In spite of the considerable growth in SPEH. 1:1. In the case of catalysis by Fe complexes.5·10-4 mol/l Ni(II)(acac)2 without additives or in the presence HMPA) is less effective catalyst of ethylbenzene oxidation into PEH in comparison with {Ni(acac)2+18C6} (Figure III. at that. the small effect of increase in SPEH (L2=HMPA) was established or SPEH did not change practically (L2=DMF) [70].max and C increase: {Fe(III)(acac)3+18C6}→Fe(II)(acac)p·(18C6)q+O2→Fe(II)x(acac)y(OAc)z(18C6)n (I) Catalysis by Co(II)(acac)2 in the Presence of Ligand-modifiers L2 As in the case of catalysis of the ethylbenzene oxidation by Ni(L1)2.max the catalytic system {Co(II)(acac)2(1. As can be seen from Fig III..5·10-4 mol/l) + 18C6(3.5% at the catalysis complexes Co(II)(acac)2•HMPA and nearly coincides with SPEH.3. we observed the increase in C in the presence mono dentate ligand-modifiers L2. SPEH.max from 52% (Co(acac)2) up to 80% in the case of {Co(II)(acac)2(1.3). The appearance of PhOH in the oxidation products at the small [Co(II)(acac)2] ≤ 1.94]. III. The value w0 is increased in ∼1.max was observed at the beginning of the ethylbenzene oxidation.0·10-4 mol/l)} by parameter S·C ( S·C = 9.3.6 times at [18К6]:[Co(acac)2]=2:1 ((w0)max) (Figure III.Methods for Enhancing the Activity and Selectivity… 487 acetone dioxygenase (M = Fe(II)) (Dke 1) (Ch. The more significant effect of mono dentate ligand-modifiers L2 not only on SPEH but on C also was discovered at the increase in [Cat]0. We established that L2 (HMPA) additives increase SPEH.5•10-4 mol/l).max ~ 86%. Scheme 4) that results in the SPEH.3]. This effect of increase in both parameters SPEH and C depended from catalyst nature and was established for Ni(II)(acac)2 only.57. In the case of catalysis by Ni(II)(acac)2 at the low catalyst concentration (0.3.0·10-2 mol/l [8.max but do not change the conversion of the ethylbenzene oxidation into PEH.max =72.2.10) [8.0·10-4 mol/l)}. But SPEH. at the addition of an aqueous solution of 18C6 to the Co(II)(acac)2 solution. catalyzed by the relatively low Co(II)(acac)2 concentration (0.5—1.%) ≈ S·C in the presence of 1.57].5-5)•10-4 mol/l seems to be due the catalyst transformation in the new catalyst not active in PEH decomposition. an increase in absorption intensity of acetylacetonate ion (acac)¯ and a . and Hacac (……).3. crown unseparated ion-pairs [56]. Figure III. The similar changes in the intensity of the (acac)¯ absorption band and shift of absorption band are characteristic for narrow. Mosolova and Gennady E.5·10-3 cm-1) to 290 nm (∼34.5·10-4 mol/l. which correspond to the absorption maximum of acetylacetone. 200C.mixture {Co(acac)2 + МP} (─ • ─•). Absorption spectra of aqua solutions: of Co(II)(acac)2 (1−−−). Larisa A. . Figure III.10. mol/l) on [18C6] or [HMPA] in the beginning of the ethylbenzene oxidation (10 min) at the catalysis by {Co(II)(acac)2+18C6} or {Co(II(acac)2 + HMPA}. mixture {Co(acac)2 + 18C6} (−−−). Zaikov bathochromic shift of the absorption maximum from ∼ 280 nm (∼35. The formation of a complex between Co(II)(acac)2 and 18C6 occurs at preservation of ligand L1 in internal coordination sphere of Co(II) because at another case.11. Matienko. [Co(acac)2]=1.488 Ludmila I. [L2]•104 (mol/l). 1200C.3. Dependence of parameter w0 (•10-4.5·10-3 cm-1) take place. the short-wave shift of the absorption band should be accompanied by a significant increase in the absorption of the solution at λ = 275 nm. PhOH (3. The Co(II) Co(III) transition under the action of peroxide radicals seems to be the most probable.3. The analogy of ethylbenzene oxidation phenomena in these two cases of catalysis by {Co(II)(acac)2+18C6} and {Co(II(acac)2 + HMPA} seems to be due similar mechanism of catalyst transformation (see Chapter III. III. 57]. are observed also at the catalysis by complex of Co(NO3)2 with 18C6 (2Co(NO3)2•18C6•6H2O) in the absence of (acac)¯− ligand [94]. the kinetic curves of the ethylbenzene oxidation products have characteristic inflections apparently caused by formation of complexes providing higher selectivity of ethylbenzene oxidation into PEH (Figure III.4).Methods for Enhancing the Activity and Selectivity… 489 Figure III.4).max accompanied by decreases in rates of AP and MPC formation. The similar complexes were assumed at the research of cumyl ROOH decomposition in the presence of adducts Co(II)(acac)2·Py (L1=acac-.70]. At the catalysis by {Co(II)(acac)2+18C6} system. did not follow the mechanism of the oxidation of (acac)¯ ligand with the molecular oxygen. The formation of Co(II)(acac)2 .12. The effects of increase in SPEH. Kinetics of PEH (1. catalyzed by Co(II)(acac)2. the addition of monodentate ligand MP to the Co(II)(acac)2 solution leads to insignificant decrease in absorption intensity of (acac)¯ ligand and hypsochromic shift of the absorption maximum (spectrum).3.5·10-4 mol/l.2). [18C6]=3.67. in the ethylbenzene oxidation.12.68]. In the presence of Co(II)(acac)2 and additives of 18C6 (or HMPA). likely.3. [Co(acac)2]=1.2).0·10-4 mol/l. L2=Py (Py=pyridine)) [8. As mentioned above.13) [8. Unlike 18C6. This fact probably testifies in favor the interaction of Co(II)(L1)2·18К62 with RO2• radicals with the formation of active selective catalyst of structure [Co(III)(L1)2·18К62·(RO2⎯)]. 1200C. The same changes in spectra are observed at the coordination of Ni(II)(acac)2 with MP (Figure III. the rate of accumulation of the products is maximum at the early stages of the reaction and passes through a minimum as the degree of oxidation increases. catalyzed by system {Co(II)(acac)2 + HMPA}. the formation of active selective catalyst in the ethylbenzene oxidation.3) and in the presence (2.3.4) of 18C6. and in the case of the coordination of axial monodentate ligands with the other metal acetylacetonates [57. in the absence (1. 490 Ludmila I. established by us for complexes of the Ni salts with 18C6. As one can see before the Co(II)(acac)2 transformation.5·10-4 mol/l. The transformation of the Co(II) salts 3 (Co-18К6) occurs in the absence of ligand L1 (L1=(acac)-).57] evidently takes place in the course of the ethylbenzene oxidation.modifier L2.3) and in the presence (2. Larisa A. Zaikov complexes with peroxide radicals in the {Co(II)(acac)2+ROOH} system was not registered. Figure III. [18C6]=3. Scheme III. The transformation of the Co(II) salts with crown-ethers depends on the nature of crown-ether and does not occur with complex 2Co(NO3)2•15C5•6H2O (4). oxidation [7. AP and MPC – also parallel (wAP/wMPC≠0 at t→0) throughout the reaction of ethylbenzene oxidation.93]) unlike the tendency.2).%) (4) [33. (4) are more effective catalysts of the ethylbenzene oxidation into PEH in comparison with system {Co(acac)2·18C62} (S·C = 15. At the coordination 18C6 (HMPA) with Co(II)(acac)2 (1.0·10-4 mol/l. . catalyzed with Co(II)(acac)2 in the absence of ligand .1).2. catalyzed by Co(II)(acac)2. and seems to be due to a result of interaction of 3 with RO2• radicals with the formation of active selective catalyst (Scheme III. By parameter S·C the complexes of the Co(II) salts with 18C6 or 15C5 (3).4) in the ethylbenzene oxidation.4) of 18C6. Mosolova and Gennady E. The products PEH.%) (3).2). the sequence of products formation of the ethylbenzene oxidation is unchanged. Matienko.3.8·10-2 (%.5•10-4 mol/l). S·C = 14. in the absence (1.3·10-2 (%. Analogy tendency for the ratio of the rates of accumulation of products PEH.3.3.3. [Co(acac)2]=1. Kinetics of AP (1. 1200C. AP and MPC were established to be formed parallel (wP/wPEH ≠ 0 at t→0).13. AP and MPC to change for reaction time t→0 was observed at the catalysis by complex of Co(II) salt Co(NO3)2 with 18C6 (2Co(NO3)2•18C6•6H2O (3)) (Table III. as a result of (acac)¯ ligand. MPC (3. In the latter case.4. TRIPLE CATALYTIC SYSTEMS INCLUDING BIS (ACETYLACETONATE) NI(II) AND ADDITIVES OF ELECTRON-DONOR COMPOUND L2 AND PHENOL AS EXO LIGANDS One of the most effective methods of control of selective ethylbenzene oxidation into αphenylethylhydroperoxide with dioxygen may be the application of the third component of the catalytic system. the conversion degree C (at SPEH ~85 to 90%). MP. the value of SPEH is high (about 85 to 90%) both at the beginning of the reaction and at the significant depth of the process. and [МP] = const = 7·10-2 mol/l. catalyzed by Ni(II)(acac)2 in the absence of ligand-modifiers L2 the sharp decrease of rate and selectivity at the initial stages of oxidation is connected with formation of complex Ni(II)(acac)2·PhOH that was an effective inhibitor of the ethylbenzene oxidation: under the action of Ni(II)(acac)2·PhOH.1. Li). phenol (PhOH). For example. the dependence of SPEH on C has a well-defined extremum. at the catalysis by {Ni(II)(acac)2 + MP} SPEHmax =85 to 87% at C ~ 8 to 10% (Figure III. and also Ni(II)(acac)2·PhOH terminated the chains of oxidation reacting with RO2• radicals [3.1). In this case. 1200C.6·10-4 mol/l (Δ.Methods for Enhancing the Activity and Selectivity… 491 III. in comparison with catalysis by binary systems {Ni(II)(acac)2+L2}. 2) or 4. Dependence of SPEH on C in reaction of ethylbenzene oxidation catalyzed by binary system {Ni(II)(acac)2+МP} (♦.4. and the hydroperoxide contents ([PEH]max). Figure III. We discovered phenomenon of the considerable increase in the efficiency of selective ethylbenzene oxidation reaction into α-phenylethylhydroperoxide with dioxygen in the presence of triple systems {Ni(II)(acac)2+L2+PhOH} (L2=MP. as one can see higher.5-6]. HMPA MSt (M=Na. along with Ni(II)(acac)2 and the additives of electrondonor ligands L2 (L2= MSt (M=Na. unlike the catalysis by {Ni(II)(acac)2 + L2}. . 1) and two triple systems {Ni(II)(acac)2+МP+ PhOH} with [PhOH]= 3·10-3 mol/l (□. parameters S·C. heterolytic decomposition of PEH into PhOH and acetaldehyde took place. we established that in the reaction of the ethylbenzene oxidation. 3) and [Ni(II)(acac)2] = const = 3·10-3 mol/l. HMPA) [69].4. Li)). Previously. %) 15.0·10-3 mol/l) + PhOH (3.1. that is higher than [PEH]max for all binary catalytic systems {Ni(II)(acac)2 + L2} studied by us earlier and also the most effective triple catalytic systems {Ni(II)(acac)2 + L2 + PhOH}.50 11. [Ni(II)(acac)2] = const = 3·10-3 mol/l. 120°C.1). Matienko.2.0·10-2 21.20 11. Parameter S·C ∼ 30. Dependence of parameter S·C·10-2(%.2237050.0·10-3 mol/l) + NaSt (3. phenomenal results were obtained in the case of application of system. [MP] = const = 7·10-2 mol/l.6 -1.4.30 17. the authors are L. Concentration [PEH]max = 1.0·10-2 20. Matienko and L. Larisa A.4. Russian Academy of Sciences. Table III.492 Ludmila I. .4. Mosolova.%) on [PhOH] in reaction of ethylbenzene oxidation catalyzed by {Ni(II)(acac)2+MP+PhOH}.0·10-3 S·C·10-2 (%. Mosolova and Gennady E. Registration date is 11. mol/l 0 0.0·10-2* S·C·10-2(%.2.4.65 Figure III.A. patent holder is Emanuel Institute of Biochemical Physics. [МP].0·103 mol/l)} (Table III.29 11.I.0·10-3 3.%) is much higher than in the case of the other triple systems and the most active binary systems [33].8 mol/l (∼27 mass %).2004. including NaSt as L2 {Ni(II)(acac)2 (3.0·10-3 5. Zaikov As is evident. mol/l 1.41 17.0·10-2 7.1·102 (%. These data are protected by patent RU No.47 12. Parameter C > 35% at the SPEHmax =85-87%.%) 0 0. [Ni(II)(acac)2].3·10-2 3.00 Table III.2. III. with maximum initial rate wPhOH. So the accumulation of PhOH. At catalysis by triple system {Ni(II)(acac)2+МP+PhOH} with small [PhOH]=4.0·10-3 mol/l) into the reaction of ethylbenzene oxidation catalyzed by coordinated saturated complexes Ni(II)(acac)2·2MP ([Ni(II)(acac)2] = 3. it turned out that dependence is extreme (Table III.1·10-1 mol/l) (Figure III.max is observed upon addition of PhOH (3. This presumption is confirmed by dependences of S·C on [Ni(II)(acac)2] at [PhOH]=const=3·10-3 mol/l and [МP]=const=7·10-2 mol/l ((S·C)max=17. This presumption is confirmed by the next facts. the fast increase in the concentration of PhOH right up to [PhOH] = (3-5)·10-3 mol/l (at t=0-5 h) is observed. 69].1.4. and also of S·C on [PhOH] at [Ni(II)(acac)2]=const=3·10-3 mol/l and [МP]=const=7·10-2 mol/l. [МP] = 2.4.%) at [Ni(II)(acac)2]=3·10-3 mol·l-1) (Table III.1.4.0·10-2 mol/l) + PhOH (3.2. selective ethylbenzene oxidation into PEH is connected with formation of the catalytic active complexes with composition 1:1:1.0·10-3 mol/l) + PhOH(4.%) at two [PhOH] concentrations differing by an order of magnitude: [PhOH] = 3·10-3 and 4. The increase in the concentration of PhOH (a result of PEH heterolysis) at the beginning of the process may be due to the function of PhOH as an acid that became stronger in consequence of outer sphere coordination of PhOH with nickel complex Ni(II)(acac)2·МP [61]. S·C reaches the extremum (S·C)max=17.0·10-3 mol/l) + МP (7. and also in the case of the ethylbenzene oxidation catalyzed by binary system {Ni(II)(acac)2(3.1.47·102 (%.0·10-3 mol/l.4.4.6·10-4 mol/l.4. [PhOH] = (3-5)·10-3 mol/l ∼ corresponds to [PhOH] for the first combination {Ni(II)(acac)2 (3.%) exceeds value S· C for complexes Ni(II)(acac)2·MP (11. The confirmation of these triple complexes formation in the process came from the comparison of kinetics of the products accumulation of the ethylbenzene oxidation catalyzed by two triple systems {Ni(II)(acac)2(3·10-3 mol/l) + МP(7·10-2 mol/l) + PhOH} at [PhOH] = 3·10-3 or [PhOH] = 4.5 and (S·C)max =18.6·10-4 mol/l.4. Observing the significant synergetic effect of parameter S·C increase under catalysis by {Ni(II)(acac)2 + L2} in the presence of inhibitor phenol may be explained by unusual catalytic activity of formed triple complexes Ni(II)(acac)2·(L2)·(PhOH). testify to the fact that in both of these cases.4. Concentration [MP] = 7·10-2 mol/l corresponds to formation of complexes of Ni(II)(acac)2 with MP of structure 1:1 (in the absence of PhOH) [8.%)) and coordinated saturated complexes Ni(II)(acac)2·2MP. It is characteristic that the value (S· C)max 2 =17. but not the consumption.12·102 (%.0=wPhOH.). .9·10 (%. Maximum value of S·C is reached at [MP] = 7·10-2 mol/l (Smax=85-87%). In the latter case.6·10-4 mol/l accordingly (Figure III. III.4). presented in Figure III.2.0·10-3 mol/l)} and to the formation of complexes of structure [М(L1)2·(L2)·(PhOH)] (Figure III.). While investigating dependence of parameter S·C on [МP] in oxidation reaction in the presence of {Ni(II)(acac)2 + MP + PhOH} at [Ni(II)(acac)2]=const=3·10-3 mol/l and [PhOH]=const=3·10-3 mol/l (120°С). The data. Some differences observed at the initial stages of two reactions are caused by the different initial conditions of triple complexes Ni(II)(acac)2·(L2)·(PhOH) formation in the course of catalytic ethylbenzene oxidation in these cases.5·102 (%.2).3 (2)).6·10-4 mol/l)} at [МP] = 0 [69].Methods for Enhancing the Activity and Selectivity… 493 Mechanism of selective ethylbenzene oxidation into α-phenylethylhydroperoxide in the presence of triple systems is demonstrated here on the example of {Ni(II)(acac)2 + MP + PhOH} system. 1200C. Previously.0)•10-2 mol/l.494 Ludmila I.4.0·10-3 mol/l)+МП(2. Zaikov Figure III.0·10-3 mol/l)}. The rate of PhOH consumption is actually unchanged in a wide interval of MP concentration (0.3÷7. Figure III. it was established that the rate of RO2• formation in the ethylbenzene oxidation catalyzed by . Kinetics of accumulation of PhOH in reaction of ethylbenzene oxidation catalyzed by binary system {Ni(II)(acac)2+МP} (1) and two triple systems {Ni(II)(acac)2 + МP + PhOH} with variable values of [PhOH] = 4.6·10-4 mol/l (2) or 3·10-3 mol/l (3) and [Ni(II)(acac)2] = const = 3·10-3 mol/l. 1200C.3.0·10-3 mol/l)}with [PhOH] = 3·10-3 mol/l (Fig III.1·10-1 mol/l)+PhOH (3.0·10-2 mol/l) + PhOH (3. The consumption of PhOH at the beginning of the process in the presence of catalytic system {Ni(II)(acac)2 (3. Mosolova and Gennady E. Larisa A. Matienko. PhOH + RO2•→.4.4. The dependences of SPEH (◊) and [PhOH] (□) от C in reaction of ethylbenzene oxidation in the presence of triple system {Ni(II)(acac)2 (3.3 (3)) may be due to the formation of the triple complexes [М(L1)2·(L2)·(PhOH)] and least of all due to consumption of PhOH as inhibitor in the reaction of chain termination.4.0·10-3 mol/l) + MP (7. and [МP] = const = 7·10-2 mol/l. E.M. Chem..M.K. Rev. which are not transformed in the course of ethylbenzene oxidation. 29. N. Dissertation of candidate of science. 317 (1974). New York: Plenum Press (1967). Z. 1976.0·10-3 mol/l)} and {Ni(II)(acac)2 (3.0·10-3 mol/l) at the addition of MP increased significantly due to the increase in the activity of the formed complexes Ni(II)(acac)2·MP in the reaction of chain initiation and homolytic decomposition of PEH [8. together with the {Ni(II)(acac)2 + L2} catalyst in the reaction system in the initial stage of ethylbenzene oxidation. Denisov. Kinetika I kataliz. Maizus.T. REFERENCES [1] [2] [3] N.0·10-3 mol/l)} allows assuming the analogous mechanism of selective catalysis realizing by triple complexes formed in the course of oxidations. 26].0·10-2 mol/l) + PhOH (3. Maizus. Increase in SPEH during the catalysis by complexes Ni(II)(acac)2·L2·PhOH (L2 = NaSt. Emanuel.0·10-3 mol/l) + MP (7. In the presence of the exo ligand L2. In the absence of the exo ligand L2. 15. 29. translated by B. 47.J. the introduction of phenol. Also. Usp.K. Matienko. Usp. Li) in the reaction of selective ethylbenzene oxidation to α-phenylethylhydroperoxide was associated with the formation of extremely stable heteroligand complexes Ni(II)(acac)2·MSt·PhOH. which resulted in considerable increase in the conversion of ethylbenzene to PEH and the yield of α-phenylethylhydroperoxide. Emanuel. Moscow.M. the coordination of PhOH to Ni(II)(acac)2 (complex 1:1) is favorable to heterolytic decomposition of PEH and inhibition of the ethylbenzene oxidation [3. the formed triple Ni(II)(acac)2·L2·PhOH complexes. Hazzard. L. E. are the effective catalysts of the selective ethylbenzene oxidation to α-phenylethylhydroperoxide with molecular O2. 1409 (1960) (in Russian) [Russ. is one of the most efficient methods of designing catalytic systems for the ethylbenzene oxidation to α-phenylethylhydroperoxide. Similarity of phenomenology of the ethylbenzene oxidation in the presence of {Ni(II)(acac)2 (3. Emanuel.T. The high efficiency of three-component systems {Ni(II)(acac)2+MSt+ PhOH} (M= Na. Candidate Thesis in Chemical Sciences. [4] [5] . Moscow: Institute of Chemical Physics.I. MP) in comparison with non-catalyzed oxidation is connected with the change of direction of the formation of side products AP and MPC (AP and MPC are not formed from PEH.Methods for Enhancing the Activity and Selectivity… 495 Ni(II)(acac)2 (3. (in Russian). that include PhOH. the PhOH becomes both effective as a deactivating ligand and as an effective activating ligand. Interesting phenomenon was established.0·10-3 mol/l) + NaSt (LiSt) (3. MP). The advantage of these triple systems is a long-term activity of in situ formed complexes Ni(II)(acac)2·L2·PhOH. Matienko. Depending on the ligand surrounding of nickel ion. Khim..I. 645 (1960)]. L. Academy of Sciences of USSR. Liquid-Pase Oxidation of Hydrocarbons. 1329 (1978) (in Russian). as it takes place in noncatalyzed oxidation) and also with hindering of heterolytic decomposition of PEH [69]. Apparently. khim. N. 5-6].0·10-3 mol/l) + PhOH (3. Z. Denisov. the parallel formation of PEH and side products AP and MPC is established in these two cases: wP/wPEH ≠ 0 at t→0 (P=AP or MPC) and wAP/wMPC≠0 at t→0 at the beginning of reaction and in developed reaction of ethylbenzene oxidation catalyzed by {Ni(II)(acac)2+L2+ PhOH} (L2 = NaSt (LiSt). L.A. Hou.K. K.K. Mosolova..21. B. L.K.. K. 6379 (2001). A: Chem. 55 (1999) (in Russian). Catal. Matienko. J. Coord. Gray. Bale. K.W. Velusamy. Tao. 113. Soc. S. T. In: Reactions and Properties of Monomers and Polymers (Eds. 15 (1998).L. L.A.E. Z. 235 (1996). Inorg. 10832 (2008). Kinetika i kataliz. Catal. Matienko. Kardasheva. N.. Chem. 145 (2007). Ser. Z. Madan. Skibida.A. Sarjeant. Raja. A. Model’naya Reaktsiya (Oxidation of Ethylbenzene. 220. Ellis. 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Haruštiak.A. Am.P. Chem.L. 2094. Straganz. 235 (in Russian). J. Matienko. Oxidation comm.V. (2005). J. Kasaikina. Chem. (Eds. 44. J. 2006) p. 2007) p. Chem. Yamaguchi. Chem. Catal. e. Siegbahn Per. J. 7466 (2006). 12306. K. B.S. [64] Q. 177181. Izv. Khim..H. I. Ph. [63] L. Khim. M. 34. V. 35. J. [44] J. I. Y. Asian J.M. Ilavsky. [56] J.I. Chem. Koverzanova. Chem. Chem.. 9. Press. Chem. 873 (1997). Soc.P.M. Golodov. Khim. Mosolova.T.A. McManus) (Washington: Am. T. Burlakova. [41] K. [57] L.. [45] M. V. Wang. Maximova.V.L. Juffa. 750 (1998).. Buschmann. [53] V. E.A.. Tokyo. Ser. R. L. Busch. 46. Chem. Soc. Skibida.. Mak. AN. N. 105 (2000). K. Pamin. Revs. Matienko. Coord. Matienko. J. 162.. Zaikov [68] L. A: Chem.. L. In: Chemical Physics and Physical Chemistry: Step into the Future (Eds. 8. Mosolova and Gennady E. Gutmann. [70] J. Zaikov and G. Mol. Chem. Kirshenbaum) (New York: Nova Sience Publ. Inc.498 Ludmila I. Mosolova. [69] V.I. 2007) p. L.. . Matachowski. E.: G. J.A. Larisa A. 225 (1976). Haber. Catal. Poltowicz.57. 19. 539. 526 alkylation. xv. 183. xv. 536 acylation. 555 adenocarcinoma. 187. 247. 109. 498. 383. 220. 9. 445. 310. 522. 282. 259. 51. 252. 524. 523 alkenes. xvi. 48. 425. xv. 325. 125. 147. 134. 376. 117. 556 adducts. 233. 377. 288 activated carbon. 368. 221. 452. 138. 437. 234. 400. 324. 215. 192 agencies. 522. 524. x. 374. 222. 18. 533. 437. 107. 505 algorithm. 4. 339. 191. 303 acrylonitrile. 425. 534 activation energy. 523 accounting. 217. 145. 525. 437. 62. 18. 30 activation. 187. 136. 234. 179. 381. 254. 373. 546. 118. 139 aluminium. 118. 237. 110. 159. 469. 149. 115. 530. 544. 538. 497 alkaloids. 523 . 209. 418. 385. 213 aggregation. 123. 83. 323. 526 acidity. 451. 440. 234 acetone. 26. 128. 26. 327. 193. 324. 329. 452 acidic. 470. 383. 444. 228. 554. 80. 83. 150. 115. 326. 534. 399 active site. 122. 206 agriculture. 396. 11. 235. 237. xiii. 544 academic aspects. 139. 267 additives. 174. 49. 332. 523 alcohols. 552.INDEX A absorption. 253. 21. 534 acceptors. 220. 504. 7. 446 aerogels. 234. 526. 124. 461. 7. 70. 138 aluminum. 523. 124. 355. 380. 25. 472. 392. 251. 177. 136. x. 509 adhesives. 552. 304. 76. 408. 118. 498. 492. 417. 525. 288. 542. xvi. 288. 342. 316. 534 accessibility. 188. 180. 320. 368. 406. 21. 8. 374 activation parameters. 556 acetic acid. 526. 263 alkylarens. 160 acrylate. 389. 551 acetonitrile. 25. 354. 551. 122. 300. 440. 522 aldehydes. 548. 387. 524. 532. 26. 80. 235. 233. 407. 417. 200. 368. 365. 291. 348. 465. 426. 394. xii. 530. 25. 525. 366. 51 active centers. 549. 526. 505 adamantane. 9. 521. 29. 544. 48. 138. 305. 16. 498. 115. 324. 373. 7. 423. 19. 281. 428. 280. 531 acetylation. 310. 10. 401 adsorption. 501. 368. 327. 26. 139 active oxygen. 441. 331. 429 acetophenone. 74. 178. 283 acetaldehyde. 235. 254. 262. xv. 280. x. 527. 219. 31. 444. 542. 522. 207 AFM. 218. 198. 252. 497. 378. 382. 19. 20. 25. 349. 47 acceleration. 534. 321. 437 air. 418. 247. 546 acceptor. 267. 152 adaptation. 49. 336. 550. 69. 47. 65. 122. 12. 11. xiii. 20. x. 189. 113. 262. 129. 179. 185. 108. 408 AlR3. 253. 48. 262. xi. 330. 450. 223. 554 absorption spectra. 18. 470 alkoxycarbonylation. 261. 309. 471. 344. 535. 402. 144. 396 alkanes. 474 acrylic acid. xiii. 440. 76. 198. 421. 49. 383. 442. 112. 533. 317. 283. 451. 165 aliphatic amines. 184. 274. 271. 387. 24. 206. xiv. 501 alkylation reactions. 26. 353. 442. 368. 54. 424. 449 biomaterials. 509 Bruker DRX. 74. 314. 2. 527. 296. 251. 213. 535 aromatic rings. 462. 198. 251. 337. 25. 154. 114. 542. 262. 66. 63. 78. 313 Brazil. 535. 446 benefits. 321. 501 ammonium salts. 243. 280. xiv. 239. 217 Beijing. 485. 392 biological systems. 233. 303. 7 aniline. 51. 166. 429. 280. 266 benign. 306. 82 B Baars. 347. 212. 15. 536. 48. 26 cancer cells. 110. 492. 212 biodiesel. 160. 320. 305. 549. 257. 233. 390. 365. 200 building blocks. 213 ascorbic acid. 115. 113. 166. 489. 234. 496. 508 capillary. 534. 525 BMI. 494. 163 awareness. 549 branching. 538 amides. 118. 265 breakdown. 49. 234. 280. ix. 294. 430. 436 biofuel. x. 544. 439 atmospheric pressure. 250. 165. 223. 467. 378. 251. 151. xvii. 124. 155. 386. 140. 545 attachment. 303. 497. 206 behaviors. 263. 440 BTC. 183. 543. 116. 502. 228 biochemistry. 10. 177 analgesic. 200. 291. 61. 109. xi. 3 anchoring. 436 butadiene. 548. 260. 247. 143 asymmetric hydrogenation. 306. 546 automation. 249 anticancer studies. 291 atoms. 120. xvii. 551 bonds. 457.500 Index basic raw materials. 485 benzene. 372. 14. 302. 466. xi. 146. 26. 113. 30. 250. 7. 504 asymmetry. 61. 144. xvii. 29. 174. 83. 23. 421. 525. 519 by-products. 366. 8. 205 biomedical applications. 13. 436 bioremediation. 222 bioenergy. 256. 509 biopolymers. 54. 107. 539. 48 biologically active compounds. 250. 112. 384. 282. 148. 246. 556. 557 aqueous solution. 23. 248. 20. 145. 371. 356 Au nanoparticles. 23 Aspergillus terreus. 137. 455. 263 ammonia. 501 amino acid. 52. 242. 5. 138. 129. 436. 251. 122. 246. 456. 420 binding energies. 199. 438. 197. 265. 28. 298. 457. 204. 535. 219. 249. 392. 16. 351. 532 bis. 24. 128. 471. 261 antidepressant. 350. 8. 163. 545. 29 auto acceleration. 316. 156. 174. 436. 176. 284. 529. 116. 24. 5 argon. 470. 456. 524. 77. 552 aqueous suspension. 134. 76. 299. 494 amine. 348. 189. 137. 355. 525. 254. 536 barriers. 262. 536. 20. 388. 524. 544. 25. 212. 11. xv. 243. 159. xiv. 48 arc-plasma method. 294. xiii. 271. 366. 14. 298. 161. 435 bending. 18. 146 antipyretic. 294. 167. 241. 101. 469. 316. 7. 367. 316. 139. 549 amorphous polymers. 153. 311. x. 216 asymmetric chemistry. 14. 159. 262. 157. 490. 235. 383 application. x. 357. 258 aminocarbonylation. xvii. 529. 532 biocatalysts. 472. 490. 235. 216. 448 C . 29. 312. 266 biodegradability. 499. 166. 185. 17. 544. 483. 487. 290. 521. 8. 281. 108. 150. 235. 125. 234 basicity. 12. xi. 187 aromatics. 258 biomass. 148. 10. 464. 532. 509 anticonvulsant. 266 automatization. 37. 285. 456. 469. 146. 247. 283. 545 biocatalysis. 149. 210. 20. 297. 62. 8. 153. 267. 79. 307. 390 aromatic compounds. 20 bonding. 212 biological activity. 166. 269 carbohydrate. 501 Butcher. 211. 257. 205. 532 breast cancer. 368 atmosphere. 377. xii. 183. xv. 130. 248. 158. xiii. 399. 246. 535. 249. 150. 415 bacteria. 25 ARCO and Halcon processes. 81. 383 anatase. 308 asymmetric synthesis. 164 binuclear. 536. 226. 260. 329. 400. 244. 298. 426. 273. 439 combustion. 145. 438. 123. 372. 319. 212. 263. 399. 242. 288. 320. 287. 266 chemical inertness. 49. 523 castor oil. 202. 383. 527. 28. 227. 228 carbon materials. 449 cervical cancer. 509 cesium. 256. 435. 536 C-C. 163. 421. 285. 244. 233. 262. 510. 47. 437. 224. 110. 220. 90. 145. 234. 26. 438. 124. 426. 252. 258. 294. 239. 11 carbonyl groups. 234. ix. 246. 11. 118. 235. 245. 509 cell line. 384. 110. 130. 73. 194. 314 carbonylative Sonogashira coupling reaction. 32 clarity. 236. 234. 441. xii. 366. 372. xv. 403. 329. 435. 83. 5. 522. 267. 287 chemical reactions. 224. 421. 202. 457 carbonylative. 62. 234. 261. 300. 426 CNS. 311. 108. 451. xvi. 310. 235. xiii. 10. 419 chromium. 377. 350. 266 closure. 521. 547 501 chain termination. 183. xi. 339. 524 carbon dioxide. 401 chromatograms. 498 coenzyme. 238. 259. xii. 27. 525 cobalt. 442. 236. 290. 242. 25. 15. 487 chloroform. 260. 233. 125. 243. 258. 450. 137. 109. 108. 63. 449 cellulose succinoylation. 210. 468 cleaner processes. 117. 523. 54. 233. 400. 545 cocatalyst. xvii. 265. 440. 228. 444. 7. 92. 282. 56. 152 chitin. 254. 211. 259. 262. 366. xi. 276. 374. 29. 93. 339. 448. 422 Cinchona alkaloids. 248. 521 catalytic activity. 342.Index carbohydrates. 121. 214. 282. 203 catalyst deactivation. 242. 87. 261 carboxyl. 198. 446 carbonylation. 247. 536 collagen. 379. 202. 7.뫰535. 17. 47. 365. 488. 116. 250. 125 chemical. x. 280. 139. 238. xv. 255. 445. 15. 52 classes. 69. xiii. 256. 269 chromatography. 48. 28 carbon atoms. 248. 143. 266. 368 chiral center. 246. 147. xviii. 352. 545 catalytic properties. xi. ix. 307. 444. 444. 309 Carbon monoxide. 108. 173. 257. 537. 259. 319. 244. 122. 328. 235. 49. 287. 437. 252. 291. 143. xiv. 394 . 22. 239. 257. 293. 260. 372 chemical structures. 261. 234. 328. 234. 212. 13 chain propagation. 327. 13. 197. 422 carboxylic acids. 532 cell cycle. 285. 47 cation. 399. 387. 240. 337. 241. 456. 540. 235. xi. 13. 356. 324. 83 chiral molecules. 31. 532 carbon nanotubes. 237. 251. 422 carrier. 280. xii. 3 colon. 134. 338. 420. 400. 356 chemicals. 273. 401. 263. 176. 368 chiral product. 189. 243. 539 cavities. 242. 20. 311. 8 commodity. 447. 254. 214. 237. 446 carboxylic acid. 19. xii. xiv. xiii. 17. 227. 397. 233. 124. 328. 262. 371. 47 cleavage. 211. 377. 549 catalytic hydrogenation. 109. 525 City. 369. 24. 233. 19. 340. 223. 24. 160. 367. 448. 96. xiii. ix. 354. 539. 24. 238. 545. 165. 48. 558 catalytic effect. 2. 441. 66. 3. 139. 16. 9 carbon monoxide. 14. xiii. 5. 8. 209. 392 clusters. 247. 259. 61. 25. 130. 7. 246. 294. 532 chemical industry. 109. 327. 536. 235. 327. 327. ix. 174. 247. 437. 428. 509 color. 26. 120. 286. 473. 209. 243. 407. 280. xiii. 437. 366. 25. 183. 253. xvi. 468. 302. 9. 524. 26. 274. 88. 377. 426 catalytic step. 261. 79. 452 chlorobenzene. 366. 346. 378. 429. 234. 144 chirality. 353. 247 CO2. x. 11. 30. 316. 560 chain transfer. 509. 244. 88. 302. 173. 9. 83. 428 catalytic particles. 316. 234. 118. 399. 351. 130. 140. 118. 235. 262. 241. 532 clinical trials. 109. 402. 61. 471. ix. 537. 526. 241. 184. 3. 402. 209. xiii. 235 community. 3. 321. 509 cellulose derivatives. 387. xvii. 449 chiral catalyst. 128. 108. 307 chemical properties. 417. 257. 8. 178. 357. 23 chitosan. 304. 436. 3. 139. 528. 93. 330. xiv. 254. xiii. 344. 368 cis. 23 chlorine. 442. 254. 489 China. 213. 212. 441. 4. 266. 140. 420. 349. 66. 51. 179. 308. 402. 524 correlation. 164. 245. xvii. 349 crystalline. 538 CTAB. 155. 164. 540. 51. 26. 202. 175. 509. 503. 174 control. 173. 525 copper. 93. 15. 291 cytotoxicity. 53 defects. 2. 92. 528. 118. 279. 551 cyanide. 286. 31 contamination. 211. 269. 251. 551. 223. 367 cycles. 404. 545. 556. 211. 291. 549. 7. 282. 14. 179. xi. 174. 418. 57. 9. 6 crystallization. 332. 269. 92. 353. 310. 283. 532. 287. 527. 221. 436. xiii. 73. 548 dendrimers. 284. 559. 207. 552. 551. 535. 544. 417 compatibility. 176. 228. 555. 138. 380. 561 copolymer. x. 147. ix. 312. 233. 54. xii. 243. xiv. 345. 28. 316. 541. 522. 302. 76. 556. 185. 74. 29. 213. 311. 148. 203. 538. 192. 538. 204. 288. xv. 29. 23. 160. 143. 195. 357. 25. 121. 26. 392. 218. 7. 65 decay. 22. 298. 224 copolymers. 197. 546. 290. 238. 247. 505. 357. 54 decomposition temperature. 174. 332. 57. 212. 202. 421 conjugation. 461. 499. 534. 453. 351. 375. 255. 535. 546. xii. 269. 234. 365. 212. 207. 263. 20. 146. 79. 530. 485 cotton. 436. 165. 555. 61. xvii. 155. 334. 314. 529. 325. 248. 166 Department of Energy. 550. 213. 136. 161. 300. 53. 267. 216. 539. 3 cosmetics. 533. 20. 5. 17. 238. 7. 460. 467. 262. 27. 430. 204 corrosion. 285. 286 deformation. 3. 254. 329. 526. 93. 210. xvi. 52. 161. 509 Czech Republic. xv. 560 contaminant. 280 crystals. 22. 108. 204. 547. 555 crystal structure. 354. 9. 266. 326. 69. xvi. 394. 198. 202 composites. 556 conversion. 253. 5. 284. 419. 74. 544. 27. 331. 235. 402. 197. 285 concentration. 161. 83. 488. 54. 310. 248. 62. 109. 425. 403. 317. 523. 561 decomposition reactions. 291. 439 coordination. 65. 178. 285. 157 complexity. 54. 213. 120. 320. 347. 83. 270. 279. 548. 175. 328. 290. 449. 49. 539. 559 compounds. 537. 31 derivatives. 122. 548. 539. 536 competitive process. 223. 551. 159 covalent bond. 50. 258. 92. 53. 456. 496. 27. 550. 200. 551. 206. 426. 256. 262. 57. 540. 448. 526. 163. 457. 538 construction. 10. 527. 529 conjugated dienes. 543. 294. 342. 424 CS. 532. 523 cyclohexanone. 8. 23. 366. 485. 456. 560 condensation. 222. 31. 559. 517 density functional theory. 552.502 Index coupling constants. 403. 535. 80. 536. 20. 210. 227. 356. 521. 203. 547. 383. 332. 4. 222. 88. 551. 144. 28. 177 degradation. 389. 261. 53. 298. 84. 174. 65. 312. 347. 56. 550 computational chemistry. 48. 210 contradiction. 157. 543. 323. 540. . 14. 153. 526. 213. 242. 528. 258. 522. 339. 26 cyclohexane. 417. 261. 6. 156. 259. 537. 281. xiv. 463. 367. 551. 376. 527. 8. 488 cyclodextrins. xvi. 523 cyclohexyl. 303. 502 consumption. 193. 1. 7. 436 deposition. xv. 31. 386. 164. 77. 324. 548. 280. 263 D deacetylation. 546. 536. 144 computing. 534. xi. 92. 492. 525 decomposition. 422. 5. 351. 91. 406. 246. 450 composition. 178. 144. 371 crown. 316. 18. 213 cost. 510. 350. 288. 350. xvii. 47. 52. 245. 546. 5. 3. 4. 283. ix. 116. 523 cyclopentadiene. 96. 533. 427. 110. 182. 456. 261. 246. 1 complement. 418 conductivity. 159. 399. 359 Denmark. 10. 16. 419. 256. 166. 145. 82. 3. 381 compilation. 525 crystallites. 335. 559. 373. 177. 214. 523 cyclohexanol. 53. 321. 549. 522. 526. 65. 390. 452 coumarins. 544 conservation. 560. 212 configuration. 9. 215. 485. 429. 521. 247. 530. 235. 18. xiii. 315. 191. 27. ix. 561 cooling. 234. 374. 554. xii. 319. 523. 366. 8. 158. 154. 408 critical analysis. 488. 178 creativity. 151. 160. 209. 421. 26. 387. 292. 549. 389. 326. 197. 428. 267. 321. 299. 24. 69. 419. 390. 388. 268 dispersion. 525 endothermic. 426 electronic spectroscopy. 347. 397. 423. 387. 386. 285 electrodes. 445 elucidation. 525 distillation. 350. 527. 163. 544. 546. 372 enantiomers. 327. 115. 447. 31 drug delivery. 30 donor. 80. 524 equilibrium. 339. 151. 502 desorption. 65. 387 enantioselectivity. 160. 176. 549. 437. 532 enzymes. 438. 288. 204. 161. 268 distortions. 74. 306. 549. 185 diffusion. 81 dissociation. 305. 303. xvii. 436 deviation. 69. 27 electromagnetic waves. 296. 423. 391. 162. 423. 338. 266. xvi. 452 dimethylsulfoxide. 306. 291. 227. 391. 441. 546. 371. 56. 490 encapsulated. 437 drug discovery. 24. 177 diffusivity. 175. 285 electrospinning. 214. 366 editors. 413 Egypt. 462. 291. 225. 529. 495. 116 emission. 377 diamines. 182. 304. 392. 25. 81. 461. 444. 355. 31 electrolyte. 418. 522 developed countries. 522. 150. 332. 151. 211. 289. 544 disposition. 394. 373. 134. 9. 328. 12. 115. 546. 446. 176. 505 . 22. 501. 256. 523 destruction. 228. 524. 161. 403 diabetes. 4 electron microscopy. 213. 425 electrophoresis. 285. 526. 157. 445. 303. 365. 351. 287 DFT. 548. 160. 254. 219. 439. 302. 370. 387. 211. 467 DMAP. 318. 287 entropy. 367. 148. 286. 421. 367 engineering. 429. 329. 429. 225. 320. 161. 405. 167 dimerization. 203. 322. 226 dienes. 238. 48. 211. 74 discs. 468. 450 England. 176 electron pairs. 525 dimethacrylate. 509. 550. 190. 283. xv. 210. 241. 249. 473 dialysis. 330. xvi. 279 electrochemistry. 536 EPR. 371 diffusivities. 351. 305. 405. 266. 49. 383 drying. 23. 538. xiii. 30. 210. 437. 210. 266 diacrylates. 373. 197. 307. 390. 164 drug release. 405. 267. 443. 209. 300. 4. 276 distributed computing. xv. 552 DNA. 233. 336. 319. 206. 313. 200. 214. 163 diversity. 366 enzymatic. 176 DSC. 289. 32. 25 displacement. 51. 536. 549. 423 dream. 183. 27. 417. 422 equipment. 114. 297. 202. 492. 536. 197 energy. 527. 387. 324. 80. 425. 226. 76. xv. 534. 147. 488. 168 entanglements. 146. 81. xiv. 372 ESI. 79. 49. 162. 212. 183. 23. 179. 21 elongation. 496. 418. 179. 426. 92. 425. 523. 372 electron. 366. 404. 445 double bonds. 456. 365. 280. 335. 196. 224. 157. 528 environmental impact. 285 dyes. 435. 365. 494. 176 employment. 61. 450. 435. 527. 359 ester. 367. 285. 421. 538. 179. 521. 250. 449 discrimination. 265 electrons. 81 enantioselective synthesis. 23. 493. 377. 189. 159. 214. 496 environment. 297. 177. 128. 470. 50. 251. 212. 198 dimethylformamide. 144. 503 diffraction. 346. 382. xiii. 402. 318. 404. 430. 526. 445. 523. 280 distilled water. 556 electron cyclotron resonance. 368 503 E economical concerns. 268. 349. 151. 556 dosage. 212 dihydroxyphenylalanine. 439. 285. 69. 158. 370. 202. 331 dielectric constant. 449 DMF. 83. 155. 22. xi. 402. 396. 143. 421. 498. 530. xii. 51. 462 energy consumption. 213. 178 drugs. 304. 261. 435.Index 368. 166. 78. 437. 95. 6 emulsions. 96. 383 free radical. 128. 552 growth rate. 366 Grignard reagents. 317. 529. 368 ethers. 523 gel formation. 127. 176 FTIR. 19. 26. 525 ethylene glycol. 217. 194. 558. x. 218. 123. 15. 532. 426. 11. 438. 202. 385. 270. 522. 15. 526 formula. 222. 436 glutamate. 142 formaldehyde. 224. 195. 5. 287 glasses. 210. 321. 27. 250. 560. 25. 525 ethylene polymerization. 366 exposure. 207. 371 extraction. 265 fragments. 248. 183. 352. 146 food products. 120. 110. 223. 524. 254. 351. 417. 110. 173. xiii. 539. 402. 425. 203. 315. 183. 214. 543. 534. 6. 134. 109. 223. 188. 299. 266. 5. 386. 536 Germany. 109. 192. 225. 126. xvi. 3. 224. 228. 177. 338. 123. 6. 451 furan. 287 glass transition temperature. 446. 532. 137. 191. 435 expertise. 30 filtration. 346 financial support. 20. 530. 206 geometry. 381. 159. 213 fiber. 138. 179. 28 glycerin. 223. 526. 226. 229. 555 ethyl acetate. 212. 525. 179. 131. 280. 531. 561 ethylene. 132. 15. 555. 26. 556. 276 functionalization. 553. 384. 21. 124. 467. x. 291. 17. 107. 203. 251. 294. 185. 217. 1. 193. 450 etherification. 457 fluid. 23 graphite. 222 FDA. 135. 174. 262. 481 esters. 209. 193. xiv. 220. 209. 190. 191. 198. 205. 511 glass transition. 449 fine tuning. 213. 31. 524. 125. 233. 28. xiv. 180. 114. 303. 366. 29 formamide. 549.504 Index fluorescence. 201. 6 films. 189. 158. 216. 551. 15. 30. 268. 418. 120. 526. 98. 559. 324. 6. 221. 76. 53. 205. 178. 444 fouling. 4 glucose. 134. 135. 554. 436 evaporation. 29. 557. 65. 305 first generation. 198. 538. 213. 550. 203. 327 granules. 185 gelation. 189. 214. 528 excitation. 130. 212. 205 fibers. 121. 249. 537. 118. 552. xv. 108. 28 gel. 546. 542. 547. 20. 161. 124. 177. 111. 551. 205. 13. 540. 327. 536. 22. 533. 211. 546. 21. 184. 176. 541. 52. 204. 266 fatty acids. xvi. 222. 498 ethanol. 215. 152. 235. 228 glycine. 176. 407. 405. 448. 162 Fourier Transformed Infra-red spectroscopy. 218. 526 freezing. 117. 525 fragrant properties. 175. 221. 27. 28. ix. 74. 199. 451 fillers. 217. 228. 52. 296. 22. 64. 175. 61 flexibility. 225. 418 greening. 119. 377 glycol. xii. 230 fluid extract. 216. 383. 548. 267. 182. 12. 276. 418 France. 108. 204. 127. 356. 22 glycoside. 116. 252. 19 grass. 293. 12. 138 European Union. xiv. xi. 269 flavor. 206. xi. 306. 197. 545. 193. 422. 266 experimental condition. 37. 212 glycerol. 371 exercise. 279. 18. 483 groups. 285 fluoxetine. 437. 227. 111. xiv. 213 Ford. 421. 223 ethylbenzene. 294 flame. 213. 179. 128. 178. 198 ethylene oxide. 424. 187. 131. xvi. 114. 118. 38 free energy. 440 G GCE. 538. 267. 24. 368. xvi. 209. 116. 130. 218. 20. 403. xiii. 370. 229. 223. 164. 200. 198. 132. 212. 183. 387. 21. 3. 6 F fabrication. 197. 489. 377 fixation. 268. 387. 216. 113. 536. 4. 538. 352. 155. 272. 173. 547. 300. 187. 122. 33. 28 GPC. 125. 313. 426 evolution. 228. 107. 25. 28. 348 foundations. 307. 203 gold nanoparticles. 166. 230 . 321. 121. 193. xiii. 544 growth. 3. 6. 522 halogens. 31 induction. 445. 21. 54. 215. 54. 445. 377. 402. xi. 421. 438. 476. 268 height. 116. 92. 195. 6 Hawaii. 452 hydrogen. 309. x. 300. 296. 183. 277. 283 high-throughput experimentation. 428. 281 hexane. 397. xvi. 526. 401. 131. 292. 545. 111. 230. 523 hydrothermal process. 444. 80. 204. 424. 342. 539. 182. 82. 122. 198. 321. 112. 228. xii. 108. 196. 536. 430. 423. 285. 181. 269. 206 hydrogen peroxide. 494 heterogeneous. 49. 425. ix. 398. 13. 357. 5. 403. 306. 202 inhibition. 182 homogeneity. 152. 213. 290. 419. 148. 116. 108. 290. 26. 23 high oxidation state. 308. 304. 227. 425 impregnation. 115. 13. 427. 179. 113. 422. 17. 560 insertion. 543. 526. 556. 531. 450 inert. xvi. 429. 192 hemicellulose. 137. 187. x. 26. 368. 162. 535. 310. 119. 349 hydrothermal. 49. 179. 66. 446. xii. 49 H-bonding. 316. 451. 161. 274 imagination. 139. 28 impurities. 535. 438 505 H hafnium. 205. 417. xi. 178. 75. 381. 29. 488 I ideal. 209. 132. 288. 509. 82. 191. 24 hydroxyl. 446. 436. 199. 527 insulators. 144. 390. 3. 233 indium. 545 hydrogen cyanide. 548. 444. 54 hydrogen atoms. 307. 189. 394 hydrophility. 227. 546. 309. 166. 200. 180. 417. 109. 7. 280 hydrazine. 190. 51. 18. 425. 186. 144. 114. 280 hypothesis. 449 hydroxyl groups. 182. 206. 558. 15. 226. 129. 421. 283. 26. 537. 436 HTE. xii. 47 homogenous. 442. 167 hybrid. 8 . 191. 165. 205. 418. 439 hydroxyapatite. 203. 281. 419. 543. 138. 294. 228. 191. 134. 27. 179. xii. 560 initiation. 307. xiii. 437. 153. 92. 65. 177. 128. 422. 91. 522 homolytic. 248. 529. xvii. 302. 465. xv. 197. 293. 176. 291. 449 Guangzhou. 9. 179. 523 hydrosilylation. 50. 4. 448. 36. 211. 300. 532. 522 halogenated. 561 inactive. 303. 125. 16. 117. 285 Homogeneous catalysts. 397. 418 immobilization. 16. 192. 546 India. 420. 19. 561 inhibitor. 67. 404. 420. 255. 167 histidine. 210. 205. 435. 21 hydrides. 219. 281. 121. 58. 114. 110. 526. 523 hydrophobic. xi. 413. 256. 227 hydrocarbons. 539 HDPE. 423. 144. 342. 48 high-capacity virtual ligand libraries. 437. 332 imitation. 140. 437. 24. xii. 522. xiv. 91. 560 host. 107. 450 hydroperoxides. 279. 393. vii. 192. 135. 286 in silico screening. 148. 49. 25. 242. 144 high-molecular compounds. 147. 52. xvii. 16. 276. 23 heating rate. 425 high density polyethylene. xv. 49. 539 Industrial. 280. 206. 298. 418. 289. 442. 283. 5. ix. 275. 250. 110. 63. 25. 176. 551 hydrogen abstraction. 203. 400. 144. 5 hydroxide. 120. 174.Index Guangdong. 2. 238. 134. 11. 310. xiv. 521 heterogeneous systems. 423. 116. 257. 449 hyperbranched polymers. 236. 9. 30. 124. xii. 81. 130. 379. 96 imino. 299. 347. 147. 526. 526 hydrophilicity. 182. 380. 522. 316. 25. 32. 292. 524 heterogeneous catalysis. 164 in situ. 538. xvi. 387 hydrogels. 536. 5 halogen. 551 hardness. xii. 436. iv. 359. 539 induction period. 297. 188. 179. 57. 400 hydrogenation. 38 hazards. 161 hydrogen bonds. 112. 305. 418. 180. 419. 179. 523 infancy. 14. 91. 173. 273. 448. 174. 381 hexenoic acids. 165. 118. 8. 248. 450 heptane. 499 hydrolysis. 274 images. 145. 522. 173. 356. 224. 301. 521. 193. 441. 529. 65. 144. 3. 398. 214. 509 image. 304. 6. 51. 384. 31. 3. 372. 118. 314 M macromolecules. 20 landscape. xvii. 237. 96. 450. 423. 514 lying. 3 ion-exchange. 116. 61. 2. 554 kinetic model. 129. 537. 202. 122. 226. 526. 446. 269. 128. 174. 316. 123. 384. 176 magnetism. 367. 138. 399 intermolecular interactions. 194 magnetic properties. 524. 522. 560 intrinsic viscosity. 115. 441. 371. 229. 546. 110. 382. 377. 61. 88. 461. 279 . 374. 217. 407. 436. 397 MAO. 339 maltose. 547. 125. 524. 452 ion implantation. 544. 436 limitations. 33. 544. 210. 20. 551. 452. x. 371. 498 kinetic curves. 372. 63 lysine. 436. 303. 159. 49. 302. 438. 440. 535 lithium. 340 manufacturing. 244. 288 liposomes. 373. 405 isolation. 534. 522. 357. 26. 304. 451. 140. 191 lignin. xvii. 260. 523 linear. 118. 456. 3. 287 linear polymers. 235. 4. 386 Korea. 96. 521. 472 isoprene. 25. 313 maintenance. 238. 28. 216. 539 majority. 535 ionization. 376. 44. 512. 191. 538. 414. 210. 385. 513. 524 low oxidation. 287. 108. 177. xv. 111. 523 linear macromolecule. 449. 124. 460 L lack of control. 193 iodine. 366. 401. 359. 122. 209 IV. 5 leaching. 381. 15. 109. 251. 489. 274. 269. 437. 114. 135. 435. 288. 27. 375. 169. 533. 259. 556 light scattering. 522 MALDI. 437. 121. xiv. 137. 120. 271. 130. 372. 15. 163 MAS. 418. 283. 440 inversion. 19. 266. 509 lead. 435. 210. 111. 51. 4. 374. 447. 94 kinetic regularities. 374. 450 interaction. 310 isomers. 137. 117. 120. 112. 121. 550 ligands. 285. 441. 535 ionic liquids. 308. 280. 368 Luo. 9. 198. 388. 399 interval. 49. 286. 11. 132. 394 IR spectra. 323. 113. 524. 442. 239. 149. 551 kinetic studies. 399. 452 loading. 435. 48. 365. 408. 446. 525. 404. 405 Israel. 25. x. 371. 215. 176. 6. 136. 114. 550. 301. 368. 398. 112. 286. 49. 265. 412 IR-spectroscopy. 23. 555. 56. 243. 211. xvi. 365. 279. 138. 89. 287. 286. 536. 209. 212. 122. 406. 383. 546. 422. 411. 440. 353. 528. 531 irradiation. 449 J Japan. 211. 165. 430. 8. 124. 282. 203. 206. 437. 4. 82. 457. 559 KOH. 527. 30 manganese. xi. 243. 245. 554. 524 localization. 539. 8. 16. 50. 400. 233. 6. 11. 422. 6. xiv. 366. 556 interface. 92. 441. 197. 283. 285 ions. 76. 437 magnesium. 405. 490. 160. 307 iron. 109. 339 iridium. 439. 30. 385. 310. 447. 107. 128. 547. 285. 436. 31. 280. 389. 163 lanthanum. 210. 174. 139. 27 liquid phase. 285. 113. 399 ionic. xv. 123. 119. 396. 372 lactic acid. vii. 408 kinetics. 447 IR spectroscopy. 83. 134. 281. 130. 222. 483 magnet. 432 K ketones. 204. 317. 126. 131. 282. 125. 31. 527 isobutylene. xv.506 Index integration. 92. 152. 521. xiii. 354. 286. 48 lubricants. 370. 448. 108. 412 liquids. 115. 25. 352. 127. 260. 451. 6. 374. 228. 211. 287 linear molecules. 51. 243. 257. 348. xiii. xvi. x. 195. 145. 8. 439. 368. 305. xv. 524 isomerization. 429. 267. 314. xvi. 212. 194 magnitude. 502 mapping. 20. 437. 425. 524 interphase. 174. 526 metal ion. 113. 139 N N/O ligands. 502. 165. 425 Ministry of Education. 26. 377 memory. 531. 202 nanometer scale. 338. 70. 451 median. xiv. ix. 1 nanometer. 368. 120. 81 MP. 23. 310. xi. 122. 23 methylene chloride. 152. 20. 228. 114. 306. 4. 456. 187 microorganism. 203. 194. 544. 371. 403. 6. 528 modules. 30. 176. 437. 117. 173. 526. 30. 257. 377. 1 metallocenes. 495 molar ratios. 299. 48. 48 metallic nanoparticle-polymer. 329 mole. 25 nanofibers. 63. ix. 12. 286. 522. 521 motif. 165. 129. xiv. 422. 48. 176 models. 266. 523. 313. 380. 29. 2. 136. 14 MWD. 281. 160. 202. 554 molecular structure. 321. 8. 534. 22. 274. 107. x. 26. 224. 2. 15. 23 microenvironment. 20. 536 modelling. 7. 115 methylene blue. 7. 316. 269. 83. 192. 371. 158. 202 molecular weight distribution. 30. 535 molybdenum. 158 molecular mass. 162. 30. 5. 437 metal nanoparticles. 554. 453 methyl phenyl sulfide. 154. 26. 287. 138. 31. 167 Mo catalysts. 52. 74 melt. 32 nanocrystals. 2. 78 NAD. 538. 148 nanocomposites. xii. x. 367. 438 MMA.Index mass spectrometry. 423. 113 molecules. 13 microwave heating. 222. 174. 265. 15. 419. 204. 285. 118. 144. 6. 276. 48 MOM. 267. 227. 7. 269 membranes. 558. 497. 258. 283. 109. 15. 158. 176. 191. 48. 12. 116. 203. 261. 285 microspheres. 109 metallogels. 65. 161. 365. 57. 7. 392. 310 modeling. 1. 455. 535. 421. 93. xi. 6. 524 micrometer. 53. 65 Mexico. 193. x. 92. 216. 49. 456. 195. x. 164. 405. 389 microwave radiation. 373 migration. 560 MPA. 287 molecular oxygen. x. 156. ix. 8 mechanistic explanations. xiv. xii. 234. 387. 213 microscopy. 177 moisture. 1. 32 mice. 183 microemulsion. 235. 9. 88. 324 monomers. 525. 225. x. 29. 74. 121. 73. 305. 457. 175. 148. 30. 229. 210. 346. 206 nanomaterials. 74. 5. 540. x. 54. 269. 532 metabolic disorder. 223. 314 modulus. 275. 163. 122. 4. 163. 189. 65. 303. 144. xvii. 16. 56. 523. 285. 200. 455. 287 melting. 408 methyl group. 128. x. 158. 134. 280. 342. 178. 24. 314. 522 media. 210 monolayer. 1. 4. 2. 20. 279. 324. 486. 174. 461. 285 Moscow. 549 microcrystalline. 200. 366. xvii. 29. 206 momentum. 471. 221. 27 Mendeleev. 174 . 109. 3. 125. 3. 392. 135. 193. 203. 24. 535. 247. 145 morphology. 536 meter. 372. 50. 127. 261 micelles. 123. 22. 134. 177. 368 morphine. 368. 428. 5. 303. 49. 212. xv. 62. 205. 320. 546 multiwalled carbon nanotubes. 556. 437. 498. 269. 291. 5. 382 metal complexes. 147. 137. 189. 48. 352 mechanical properties. 27. 5. 107. 391. 344 molybdoenzymes. 525 metals. 283. 150. xv. 175. 542. 237 MoVI complexes. x. 3. 315 messengers. 457. 144. 74. 544 metal ions. 320. 192. 277 methylalumoxane. 429 methodology. 404. 5. 437. 179. 137. 419. 471 methyl methacrylate. 29 metal oxides. 48 model system. 163. 432 mesoporous materials. 285. 532 molecular dynamics. 202 metalloporphyrins. 166 507 minors. 298 matrix. 277 mixing. 372 methanol. 267. 29 MNDO. 238. 176. 154. 464. 108. 390. 265. 49. 174. xii. 527. 205. 266. 173 novel materials. 167 Oxidation catalysis. 226. 58. 243. 472. 559. 75. 71. 61. x. xvii. 298 O obstacles. 174. 74. 128. 485 null. 148. 48. 94. 526. 234. 122. 51. 55. 77. 242. 314. 50.508 Index nanoparticles. 543. 474. 529. 197. 396. 545. 5. 209. 47 oxidation catalysts. 471. 126. 28. 48. 49 NMR. 447. 26. 486. 464. 18. 355. 167. 115. 96. 250. 203. 292. 342. 266. 498. 522. 6. 224. 488. 79. 247. 174. 75. 273. 114. 176. 392. 164. 214. 350. 11 organic polymers. 274. 437. 469. 14. 375. 485. 27. 449 noble metals. 48. 268. 534. 5. 234. xiv. 259. 228. 12. 418. 78. 27. 57. 376. 137. 226. 197. 30. 396. 113. 509 next generation. 452 NBS. 23. 82. 551. 24 overlap. 402. 494 nitrogenase. 25. 8. 163. 524. 490. 15. 443. 76. 288. 383 o-dichlorobenzene. 80. 437. 179. 96. 221. 197. 286 NH2. 452 negative effects. 62. 3. 195. 205. 522 oxide. 483. 269. 52. 228. 25. 7 Oxovanadium. 143. 30 nanostructured materials. ix. 266 nitroso compounds. 7 optimism. 285. 388. 473. 222. 125 oligomers. 436. 66. 211. xiv. 538. 251. xvii. 108. 66. 405. 55. 267. 74. 501 nucleophilicity. 400. 92. 485. 538. 300 neglect. 436. 248. 182. 96. 271. 542. 486. 4 nitrobenzene. ix. 113. 327. 193. 3. 448. 179 nanowires. 66. 499 oleic acid. 397. xvii. 467. 6. xiii. 93. 358 neurotoxicity. 550 nuclear magnetic resonance. 23. 48 oxidation products. 233. 1. 535 organic solvents. 225. 52. 7. 545. 438. 173. 214. 3. 456. 5. 386. 444. 193. 268 nucleation. 464. x. 392. 81. 527. 79. 27. 265. 119. 4. 6. 81. x. 267. 312. 69 octane. 466. 23. 309. xiii. 65. 216. 372 nuclei. 270. 80. 339. 465 N-bromosuccinimide. 523. 216. 32 nanostructures. 394. 308. 449. 292. 529. 155. 217. 78. 212. 133. 216. 354. 137. 92. 503. 351 nuclear. 195. 312. 497. 293 nanorods. 2. 273. 298. 167. 28 naphthalene. 5 oligomerization. 447. 237 osmium. 276. 536. 351. 262. 83. 457. 527. 269. 297. 435. 471 organ. 355. 10. 540. xvi. 257. 87. 23. 7. 6. 418 olefin epoxidation. 250. 323. 535 organic compounds. 175 optimization. 15. 509 nickel. 265. 491. 561 nicotinamide. 177 organic solvent. 463. 249. 63. 385. 48. 274 oxygen. 82. 26. 546. 483. 204. 70. 392 organic ligands. 234. 532. 509 N-heterocyclic carbenes. 274. 235. 167 Netherlands. 344 olefins. 109. 31. 442. 11. 550. 437. 425. 176. 15. 87. 544. xi. 455. 20. 27. 468 non-steroidal anti-inflammatory drugs. 537. 109. 554 . 497. 526 oxidative. xii. 159 nucleophiles. 435. 461. 159. 485. 353. 501 Northern Ireland. 540. 470. 548 oxidative destruction. 228. 368. 262. 483. xvi. 389. 430 organic. 429. 215. 377 OH. 52. 440. x. 487. xiii. 80. 499. 525. 398. 485. 501 operations. 455. 437 Nuclear Magnetic Resonance. 74. 65. 77. 62. 525 oxide nanoparticles. 189. 503. 546. 483. 467. 194. 29. 57. 4. 494. 227. 554 oxidation rate. 268. 85. xvi. 4. 448. 33. 49. 195. 305 NHC. 48. 370. 367 opportunities. 47. 488. 206. 537 oil. 262 niobium. 462. 492. 95. vii. 237 norbornene. 19. 419 organogels. 474. 287. 408 optical properties. 67. 477. 522. 425. 223. 528. 237. 92. 218. 233. 468. 483 organotin compounds. 48. 26 nitrogen. 192 organic mediums. 187. 497. 214. 203 organomagnesium compounds. 487. 548. 262. 489. x. 298. 387. 1 nonane. 357. 347. 337. 124. 262 PAN. 337. 293. 213. 545 partition. 134. ix. 350. 66. 373. 335. 124. 527. 536 physicochemical. 129. 157. 31. 48. 37 polar groups. 192. 48. 63. 552. 69. 311 polystyrene. 560 phenoxycarbonylation. 27. 5. 524. 199 poison. 136. 120. 146. 1. 204. 553. 124. 124. xiv. 525 polymer chain. 160. 49. 313. 417 permeation. 398. 49. 551. 314. ix. 86. 146. 559. 20. 205. 121. 1 polymer matrix. 91. 368. 228. 318. 538. 383. 22 polymer. 457 Portugal. 535 PMMA. 21. 329. 439 phenomenology. 50. 555. 223. ix. 406 polycondensation. 61. 540. 560. 203. 558 particles. 130. 280. 317. 113. 6 parallel. 155. 136. 139. 543. 530. 476. 125. 356. 534. 234. 5. 38. 138. 525 polyimide. 6. 531. 202. 456. 148. 355. 167 PCP. 109 polarity. 522. 287. 545. 299. 551 509 P Pacific. 210. 336. 525. 381. 420. 285. 114. 555. 387. 288. 366. 367. 51. 27. 536 polyethylene. 145. 365. 116. 444. 198. 82. 547. 327. 539. 394. 24. 157. 139 polymerization time. 339 polyether. 109. 534 patents. 561 phosphorus. 368 poly(methyl methacrylate). 509 play. 127. 538 parameter. 450 plasticity. xvi. 558. 134. 164 pharmaceuticals. 538. 523 polarization. 38 Palladium-catalyzed carbonylation reactions. xii. 129. 121 polymer synthesis. 291. xi. 127. xv. 123. 329. 140 polymers. 367. 528. 534. 113. 203. 7 phenolphthalein. 261 polybutadiene. 164. 348. 136. 444 polymorphism. 561 phenol oxidation. 287. 469. 197. 49 platform. 117. 422. 461. 47. 401. 313. 544. 316. 216. 436 pollution. 202 physiology. 554. xv. 129. 163. 527. 144. 120. 119. 13 PhOH. 152. 556. 524. 176 pharmaceutical industry. xiii. 525 pore. ix. 125. 394 physical properties. 382. 192. 560 parallelism. 426 Poland. 388. 422. 527. 47. 357. 8. 95. 26. 23. 108 polymerization kinetics. 145. 525 polymer composites. 178. 156. 212. 128. 29. 365. 89. 131. 204. 93. 281. 116. 139 polymerization process. 287. 113. 555 petroleum. 108. 547. xvii. 329. 436. 2. 314. 406. 538. 254. 150. 336. 312. 546. 261. 550. xiii. 547.Index oxygenation. 540. 200. 536 physics. 176 porphyrins. 1. 7. 355. 173. 109. 28. 327 peroxide. 147. 213. 12. 523. 195. 532. 116. 247. 532 plants. 120. 127. 405 phenol. 266. 386. 130. 526. 355. 261 polydispersity. 335. 287 polymerization temperature. 50 pathways. 233 phenyl esters. 29 polyamides. 135. 205. 233. 523. 252. 539. 210. 104 potassium. 350. 523 porous materials. 161. 110. 545. 207. 320. 112. xv. 302. 1. 262 phenylalanine. 268. 536 physicochemical methods. 198. 347. 336. 29. xiii. 211. 509 platinum. 205 polypropylene. 290. 247. 89. 206. 367. 394. 438 . 212. 167 perfume chemistry. 558. 52. 539. 233. 144. 368 polymeric catalysts. 391. 543. 159. 280. 285 PCA. 527. 27. 338. 175. 554. 28. 30 polyisoprene. 14. 529. 197. 368. 138. 521. 544. 406 passivation. 390. 137. 339. 291. 327. 174. 486 phase transfer catalysis. 120. 285 polyesters. 474 PCR. 303 polymeric materials. 287. 557. 327. 229. 550. 193. 13. 318. 524 portfolio. 437. 88. 556. 136. 397. 540. 4 plasticizer. 383 plastics. 121. 280 polymeric products. 317. 317 polymer molecule. 112. 129. 21. 307. xiii. 314. 392. 75. 373. 505. xi. 387. 375. 315. 417. 365. 423. 407. 301. 401. 262. xiii. 221. 225. 214. 213. 503 regression. 466. 175. 311. 277. 400. 238. 219. 315. 537. 115. 129. 140. 165 relief. 209. 390. xvi. 65. 54. 241. xi. 367. 178. 216. 391. 29 PVP. 394. 339. 371. 457. 442. 107. 293. 256. 224. 228. 78. 351. 522 reaction mechanism. 385. 509 propagation. 384. 314. 134. 405. 25. 451 purification. 426 purines. 367. 31. 124. 379. 304. 233 precipitation. 267. 74. 451. 49. 496 regioselectivity. x. 299 regenerate. 305. 18. 8. 369. 549 quercetin. 373. 527. 327. 346. 281. 377. 383. 156. 137. 373. 123. 237. 222. 110.510 Index radius. 367. 82. 38 radical formation. 492. 367. 109 pyrimidine. 357 redistribution. 286. 524 reaction medium. 149. 226. 235. 549. 263. 400. 163 proliferation. 522 reference system. 174. 167 principal component regression. 155. 224. 365. 371. 348. 550 redox. 24 pyromellitic dianhydride. 157 range. 452. 158. 302. 334. 407 pulp. 371. 492 reaction time. 367. 21. 117. 176. 531 reading. 185. 221. 483. 196. 402. 537 preparation. 385. 554. 117. 373. 162 recognition. 389. 404. 551 probe. 418. 445. 162. 252. 399. 522. 285. 357. 525 prevention. 61. 371. 392. 346. 204. 365. 4. 424. 280. 352. 139. 108. 384. 523 radicals. 375. 51. 202 rationality. xv. 118. 342. 521 rejection. 179. 266. 5. 355 Reppe and Heck. xv. 465. 7. 392. 2. 437 propylene. 535. xiii. xiv. 378. 261. 342. 448 reactivity. 555 reactive sites. 62. 372. 210. 351. 539. 532 rational design. 136. 315. 435. 399. 123. 347. xviii. 167 regulation. 125. 522. 362. 286. 548. 110 . 486. 300. 226. 381. 380. 367. 536. 311 propionic anhydride. 342. 440. 117. 423. 65. 167 probability. 217. 396 PVC. 162 PTC. 378. 471 pyrolysis. 321. 185. 91. 408. 523 proteins. 368 radiation. 370. 318. 461. 259. 211. 108. 305. 28. 395. 284 reasoning. 314. 52. 335. 283 protons. 300. 177. 28 pyridine ligands. 485. 523 reality. 53. 539 reaction temperature. 49. 399. 305. 210. 382. 401. xvi. 284. 380. 284. 209. 144. 167 quaternary ammonium. 303. 228. 219. 379. 134. 399. 287. 287. 285. 339. 420. 56. 395. 177. 128. 108. 369. 386. 327. 88. 486 reaction rate. 96 reagents. 304. 539. 544. 228. 136. 243. xv. 61. 496 reliability. 304. 216. 378. 205. xi. 254. 290. 547 propane. 48 purity. 374. 51. 165. 465. 209. 367. 257. 21. xii. 175 raw materials. 161. 399 reactants. 223. 48. 124. 397. 17. 288. 221. 82. 320. 346. 398. 242. 93. xi. 442. 293. x. 374. 457. 356. 116. 336. 457. 211. 313. 129. 435. 281. 210 principal component analysis. 225. 437. 330. 347. 292. 405. 320. 144 relevance. 378. 279. 89. xiv. 528 R race. 176. 372. 93. 226. 380 reaction center. 387. 282. 66. 235 regeneration. 350. 245. 426. 385. 65. 355. 31. 430. 246. 394. 314. 217. 523. 165. 164. 116. 350. 555. 535. 525 protection. 75. 437. 371. 212. 422. 383. 441. 210. 372. 526 radical reactions. 140. 61. 527. 282. 376. 556 radioactive carbon monoxide. 266. 23. xiii. 368. 536 recycling. 212. 440 project. 387. 379. 213. xv. 221. xv. 366. 382. 217. 3 Radiation. 527. 26 Q quantum mechanics. 436 reactant. 501. 211. 267. 389. 443. 387. 108. 407. 92. 69. 365. 273 prototypes. 350. 374. 384. 16. 369. 213. 239. xvi. 367. 110. 284. 52. 212. 524. 342. 368. 450 resistance. 267. 371 signals. 499. 22. 245. 545. 291. 178 sensitivity. 285. 51. 191 solvents. 62. 281. 317. 535 specific surface. 293. 422. 368. 228. 3. 24. 226. 204. 458 similarity. 211. 538. 108. 281. 282. 80. 544. 296. 219. 92. xiii. 120. 50. 524. 371. 114. 49 rheology. 30. 159. 69. 21. 357. 158. xv. 12. 417. 198. 269. 189. 65. 283. 408 residues. x. 265. 408 researchers. 540. 525 sorption. 83. 554 spin. 396. 21. 426. 267. 469. 357. 8. 49. 536 speciation. 456. 351. 165. 449 responsiveness. 313. 335. 163. 261 self-assembly. 371. 316 rings. 30. 554. 313. 25. 557 ruthenium. 300. 176. 62. 144. 93. 346. 556 saturation. 298. 92. 7. 26. 460. 244. 298. 464. 164 scattering. 174. 30. 367. 426. 214. 437. 369. 382. 367. 74. 390. 33. 242. xv. 387. 92. 340. 129. 195. 13 scandium. 10. 535. 14. 342. 266. 374. 407. 205. 267. 390. 551 solvent molecules. 212. 496. 158. 523. 205 Schiff bases. 4. 220. 15. 205 rhodium. 21. 486 sensors. 523. 451. 269 second generation. 216. 213. 465. 115 sponge. 17. 300. 440. 495. 464. 548 stages. 161. 21. 161. 285 SiO2. 164. 452 states. 527 spectrum. 93. 3. 282. 53. 458. 440 sodium hydroxide. 226. xvii. 33. 405. 320. 328. 283. 69. 197. 521. 206. 531. 27. 302. 559 starch. 547. 47. 352. 536 skeletal muscle. 12. 418. 556. 317. 529 simulation. 508 seizure. 312. 420. 503 Royal Society. 154 requirements. 127. 396. 420 rhenium. 173. 211. 228. 426 scaling. 82. 468. 297. 354. 524. 163. 405. 199 Spring. 488. 187. xi. 419. 296. 304. 51. 47. 115. 370 solid state. 223. 304. 2. 348. 15. 26. 536. 88. 457. 176. 521. 347. 535. 221. 285. 76. 65. 266. 185. 498. 287 solubility. 7. 353. 550. 378. ix. 162. 544 spectroscopy. 198. 544. 225. 299. 93. 384. 447. 3 skeleton. 376. 8. 236. 298. ix. 176. 245. 294. xi. 73. 29. 17. 18. 533. 532. 525. 288. 382. 285. 287. 365. 49. 429. 409 Ru catalysts. 438. xvii. 351. 476. 540. 7 shape. 204. 486. 244. 389. 377. 546. 174. 525 silicon. 356. 203. 350. 216. 536. 310. 177 shock. 243. 344. 214. xiv. 304. 26. 134. 440. 314. 555 room temperature. 392. 6. 29. 555. 399. 94. 314. 470. xvii. 355. 421. 315. 297. 121. 450. 471. 424. 251. 62. 65. ix. 266. 10 stabilizers. 48. 484. 428. 25. 240. 395. 314. 493. 7. 203 resveratrol. 439. 115. 436. 4 scarcity. 498 resources. 400. 3. 227. 210. 371 shock waves. 305. 405 resolution. 26. 344 sites. 94 species. 151. 115. 212. 400. 38 stability. 525 511 S salts. 25. 291. 523 silver. 148. 14. 224. 521 Russian Academy of Sciences. 229. 307. 543 stabilization efficiency. xvi. 391 Rh complexes. 204. 525. 307. 424 Russia. 239. 312. 426. 338. 522. 526 silica. 521. 26 stable complexes. 287 shear. 524. 265. 350. 289. 458. 79. 89.Index reputation. 216 solvent. 28. 128. 167. 419. 187. 238. 1. 211. 267. 160. 74. 365. 448 silanol groups. 16. 420. 122. 212 spectrophotometry. 195. 177 specifications. 26. 424. 406. 289. 522. 492 ROOH. 283. 61. 421. 17. xiv. 296 sodium. 216. 164. 483. 470. 537. 182 sensing. 154. 313. 463. 174. 485. 342 solid phase. 535. 5. 109. 57. 404. 23. 31. 418. 291. 216. 508 solvation. 549. 144. 372. 205. 438. 209. 21 sol-gel. 380. 284 . 523 spatial. 476 statistics. 14. 189. 529. 368. 535. 212. 235 topology. 389. 408 steric. 234. 509 transesterification. 394. 214. 307. 469. 64. 5. 291. 2 structural changes. 311. 130. 378. 316. 449. 49. 7 target. 495 sugarcane. 138. 25. 468. 325. 177. xi. 176. 150. 80. 39. 408. 92. 377. xiii. 372 supramolecular. 107. 5 tar. 455. 49. 122. 539 transformation product. 119. 356 toxic waste. 188. 205 surface area. 259. 483. 435. 372. 143. xiii. 241. 18. 412. 178. 82. 327. 312. 16 thermal stability. 9. 10. 251. 472. 74. 252. 445. 26. 405. 266. 219. 392. 21 testing. 228 transfer. 267 sulfonamides. 268. 216. 536 transformation degrees. 318 symmetry. 26. 211. 522. 283. 297. 346. 216. 389. 189. 408. 525 TEOS. 217. 307. 474. xi. 131. 367. 474. 457. 367. 450. 315. 101. xv. 244 surfactants. 53. 366. 20. xvi. 503. 526. 385 styrene. 223. xii. 198. 464. 341. 216. 70. 535 structural characteristics. 551 steroids. 6. 16. 554 transition metal. 21 thioamides. 76. 96. 472. 134. 113. 4. 117. 218. 135. 197. 234. 539 substrates. 212. 267. 112. 400. 483 sulfuric acid. 521 TCE. 288 Sun. 546 T Taiwan. 535 sustainability. 443. 102. 26. 159. 159. 203. 152. 223. 436 technology. 446 strong interaction. 179. 347. 494. 536 transition temperature. 543 transformations. 456. 422. 346. 93. 161. 5. 258. 527. 139 thin films. 161. 224. 110. 30. 228. 173. 158. xiii. 138. 213. 57. 179. 527. 462. 529. 408. 1 . 218. 20. 408 Suzuki coupling reaction. 48. 371. 258. 464. 221. 109. 455. 234. 246. xii. 487. 369. 502. 551 transition. 270. 69 storage. 404. 535 substitutes. 350. 400. xiii. 5. 161. 185. 492. ix. 49. 48. 5. 108. 239. 240. 53. 526 synergistic. 177. 526. 31 titania. 195. 128. 140. 450. 389. 356. 3. 296. 224. 18 titanium. 477 tin oxide. 471. 130. 509 toxicology. 234. 191. 483. 217. 8 TGA. 525. 522. 245. 372. 12. 282. 25. 79. 181. 530. 494 substitution. x. 61. 14. xiii. 177. 314. 544. 421. 111. 194. 258. 294. 69.512 Index TEM. 1. 378. 477. 395. 534 technological advances. 160 tetrabutylammonium bromide. 463. 163. 280. 42. 221. 362. 536 suppliers. x. 367. 377. 509 thermal analysis. 182. 143. 233 thiocarbonylation. 14. 437. 548. 176. 484. 160. 224. 226. 126. 200. 226. 366. 198. 210. 314. 27. 3 transmission. 402. 321 toluene. 348 transportation. 269. 146. 367. 319. 498. 321. 268 therapy. 389. 335. 64. 185. 523. 281. 176. 82. 22. 24. 452. 237. 209. 471. 330. 195. 89. 209. xvii. 461. 379 surfactant. 437. xvii. 155. 238. 501. 118. 260 swelling. 143. 277. 234. 110. 10. 247. 340. 305. 136. 28. 525 tones. 256. 27. 128. 212 traits. 365 tantalum. 26. 243. 151. xi. 381. 347. 464. 399 tetrahydrofuran. 204. 317. 3. 140. 190. 440. 274 thermal decomposition. 456 stretching. 173. 93. 25. 335. xi. 96. 124. 496. 420. 164 tin. 213. 132. 239. 4. 88. 455. 199. 371. 116. 187. 13. 452 sulfate. 368. 215. 285. 214. 356. 422. 337. 543 Supramolecular gels. xv. xvii. 467. 179. 452 Superoxide. 151. 532 toxicity. 176. 539. 234 three-dimensional model. 127. 150. 502. 235. 428. 242. 465. 365. 470. 214. 384. 255. 374. 139. 108. 97. 120. 536. 336. 456. 82. 523. 237. 202 temperature. 65. 2. 211. 249. 440 transport. 142. 174. 185. 209. 534. 192. 382. 344. 461. 485. 177. 31. 457. xi. 211. 158 technologies. 522. 436 stereoselectivity. 408 telephone. 297. 494 sulfur. 153. 248. 536 UV irradiation. 476. 109. 15. 436 Y yeast. 112. 189 wires. 155. 152. 396. 76. 241. 376. 320. 215. 267. 65 versatility. 437. 347. 20. 144. 9. 282. 205 vapor. 108. 27 UV radiation. 165 values. 456 vibration. 329. 561 yttrium. 150. 235 U ultrasonic frequency. 468. 383. 446 viscosity. 266 vancomycin. 24. 14 variations. 3. 239. 238. 212. 222. 406. 404. 93. 176. 31 volatility. 535 wavelengths. 197. 404. 250 tryptophan. 389. 129. 251. 175. 474. 339 worldwide. xii. 493 triggers. 472. 226. 411 waste. 127. 4 Z zeolites. 335. 82. 218. 463. 216 yield. 243. 287. 4. 217. 179. 254. 319. 19. 218. 10. 366 urea. 193. 346. 167. 227. 78. 75. 16. 290. 56. 50. 407. 83. 114. 545. 438. 400. 367. 467. 80. 317. 321. 419. 355. 550. 81. 468. 498 twist. 69. 560 vanadium. 260. 235. 216. 293. 163. 251. 89 X X-ray analysis. 143. 213 triphenylphosphine. 528 tumor cells. 375. 185. 74. 350. 137. 244. 494. 324. 466. 372 weak interaction. 20. 198. 136. 211. 337. xv. 344. 303. 405. 313. 5. 14. 356. 437 universe. 28. 49. 468. 385. 376. 381. 198. 311. 91. 9. 61. 30. 444. 128. 375. 204. 203 wood. 366. 176 triglycerides. 125. 269. 451 wastewater. 221. 437 water. 224. 250. 210. 4 zirconium. 14. 212. 285 xylene. 229. 214. 467.Index trifluoroacetate. 466. 140. 236. 283. 9. 389. 251. 79. 422. 158. 187 X-ray diffraction. 523 zinc. 244. 160. 151. 179. 175 urease. 243. 451 vision. 408 ultrasound. 280. 83. 268. 134. 438. 12. 178. 471. 210 513 W Washington. 486. 195. 331. 397. 407 uniform. 216. 451 zirconia. 130. 452 workers. 121. 439. 462. 551. 398 turnover. 350 trifluoroacetic acid. 509 tungsten. 371. 367. 62. 258. 214 variables. 53. 49. 372. 374. 378. xi. 535 V vacuum. 155 validation. 177. 93. 405. 469. 468 velocity. 296. 451. 203. 255. 450. 5. 498. 91. 323. 3. 366. 211. 401. 108. 6. 49. 157. 458. 82. 219. 426. 176. 140. 98. 450. 439 valence. 4 . 354. 211. 267. 423. 23. 397. 52. 522. 237.