Phase-transfer reactions asymmetric catalysis

BINAP, 127, 171, 191, 194, 196 olefin reaction, 126, 167, 169, 191 organic halides, 191 Pancreatic lipase inhibitors, 357 Pantoyl lactone, 56, 59 para-hydrogen, 53 Peptides, matrix structure, 350 Perhydrotriphenylene, crystal lattice, 347 Pericyclic reactions, 212 chiral metal complexes, 212 Claisen rearrangement, 222 Diels-Alder, 212, 291 ene reaction, 222, 291 olefin dihydroxylation, 150 Phase-transfer reactions asymmetric catalysis, 333... 

Arylation, olefins, 187, 190 Arylketimines, iridium hydrogenation, 83 Arylpropanoic acid, Grignard coupling, 190 Aspartame, 8, 27 Asymmetric catalysis characteristics, 11 chiral metal complexes, 122 covalently bound intermediates, 323 electrochemistry, 342 hydrogen-bonded associates, 328 industrial applications, 8, 357 optically active compounds, 2 phase-transfer reactions, 333 photochemistry, 341 polymerization, 174, 332 purely organic compounds, 323 see also specific complexes Asymmetric induction, 71, 155 Attractive interaction, 196, 216 Autoinduction, 330 Axial chirality, 18 Aza-Diels-Alder reaction, 220 Azetidinone, 44, 80 Aziridination, olefins, 207... 

The aim of this book is to provide a concise and comprehensive treatment of this continuously growing field of catalysis, focusing not only on the design of the various types of chiral phase-transfer catalyst but also on the synthetic aspects of this chemistry. In addition, the aim is to promote the synthetic applications of these asymmetric phase-transfer reactions by giving solid synthetic evidence. Clearly, despite recent spectacular advances in this area, there is still plenty of room for further continuous development in asymmetric phase-transfer catalysis. 

Many studies of asymmetric chemical conversions through the catalysis of Cinchona-derived PTC catalysts have been performed to expand the application of phase-transfer catalysis to various organic reactions. In addition to the reactions classified above, some selected examples of asymmetric phase-transfer reactions are shown below. 

Considerable efforts made for the synthesis of biologically relevant molecules by means of asymmetric phase-transfer catalysis are summarized in this chapter. Because the phase-transfer reaction is usually insensitive to the contamination of air, moisture, and even acidic or inorganic-salt impurities, and it is set up with simple and user-friendly protocols. It is recognized as one of the easiest methods for large-scale, stereoselective production of functional molecules as exemplified by the studies reported from pharmaceutical companies. In addition, ready accessibility of chiral onium salts as a catalyst facilitates an initial trial in... 

The catalytic synthesis of an enantioselective product from a prochiral reactant is said to involve asymmetric catalysis and the catalyst is called an asymmetric catalyst. Asymmetric catalysis is found in homogeneous, heterogeneous and phase-transfer reactions. - ° This area of research gained a significant momentum after the award of a 2001 Nobel Prize to the researchers working on asymmetric catalytic chemical processes. - In the case of phase transfer catalysis, the quantitative assessment of rate enhancement is not carried out in any such catalytic reaction simply because the reaction system is just too complex for such effort. Almost all reported asymmetric catalytic reactions are involved with synthesis in which the main aim has been focused on the yield of enantioselective -zso... 

Early work on the use of chiral phase-transfer catalysis in asymmetric Darzens reactions was conducted independently by the groups of Wynberg [38] and Co-lonna [39], but the observed asymmetric induction was low. More recently Toke s group has used catalytic chiral aza crown ethers in Darzens reactions [40-42], but again only low to moderate enantioselectivities resulted. 

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

Asymmetric Phase Transfer Catalysis Aldol Reactions... 

Numbers of asymmetric phase transfer catalysis can now be accomplished efficiently to give a variety of chiral non-racemic products with high enantiomeric excesses. Thus, asymmetric phase transfer catalysis has grown up into practical level in numbers of reactions and some optically pure compounds can be effectively produced on large scale by use of chiral phase transfer catalysts. 

In contrast to the maturity of asymmetric synthesis utilizing chiral transition metal catalysts, asymmetric phase transfer catalysis is still behind it and covers organic reactions to lesser extent. Thus, it is further necessary in wide range to explore efficient asymmetric phase transfer catalysis keeping its superiority of easy operation, mild reaction conditions, and environmental binignancy. 

The recent rapid progress in this area will definitely promise that asymmetric phase transfer catalysis is the reaction for the 21st century. 

M. J. O Donnell, Asymmetric PTC Reactions. Part 1 Amino Acids , Phases - The Sachem Phase Transfer Catalysis Review 1998, Issue 4, pp. 5-8. 

Asymmetric phase-transfer catalysis using chiral nonra-cemic onium salts or crown ethers has now grown into a practical method whereby a large number of reactions can be performed and some optically pure compounds can be produced effectively on a large scale. 

The publication (70) in 1976 of the preparation of optically active epoxyketones via asymmetric catalysis marked the start of an increasingly popular field of study. When chalcones were treated with 30% hydrogen peroxide under (basic) phase-transfer conditions and the benzylammonium salt of quinine was used as the phase-transfer catalyst, the epoxyketones were produced with e.e. s up to 55%. Up to that time no optically active chalcone epoxides were known, while the importance of epoxides (arene oxides) in metabolic processes had just been discovered (71). The nonasymmetric reaction itself, known as the Weitz-Scheffer reaction under homogeneous conditions, has been reviewed by Berti (70). 

Treatment of diethyl malonate and related compounds with 1,2-dihaloethane in the presence of base constitutes a classical method of cyclopropane synthesis296"300. The reaction can be conveniently carried out under PTC conditions. An improved method utilizing solid-liquid phase transfer catalysis has been reported298. The reaction of dimethyl or diethyl malonate with 1,2-dibromoalkanes except for 1,2-dibromethane tends to give only low yields of 2-alkylcyclopropane-l, 1-dicarboxylic esters. By the use of di-tm-butyl malonate, their preparations in satisfactory yields are realized (equation 134)297. The 2-alkylcyclopropane derivatives are also obtained from the reaction of dimethyl malonate and cyclic sulfates derived from alkane-1,2-diols (equation 135)301. Asymmetric synthesis... 

The representative reaction system applied in asymmetric phase-transfer catalysis is the biphasic system composed of an organic phase containing an acidic methylene or methine compound and an electrophile, and an aqueous or solid phase of inorganic base such as alkaline metal (Na, K, Cs) hydroxide or carbonate. The key reactive intermediate in this type of reaction is the onium carbanion species, mostly onium enolate or nitronate, which reacts with the electrophile in the organic phase to afford the product. 

The fate of the onium carbanion Q+R incorporated into the organic phase depends on the electrophilic reaction partner. The most studied area in the asymmetric phase-transfer catalysis is that of asymmetric alkylation of active methylene or methine compounds with alkyl halides, in an irreversible manner. The reaction mechanism illustrated above is exemplified by the asymmetric alkylation of glycine Schiff base (Scheme 1.5) [8]. 

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