Chiral phase-transfer catalysis catalysts

The epoxidation of enones using chiral phase transfer catalysis (PTC) is an emerging technology that does not use transition metal catalysts. Lygo and To described the use of anthracenylmethyl derivatives of a cinchona alkaloid that are capable of catalyzing the epoxidation of enones with remarkable levels of asymmetric control and a one pot method for oxidation of the aUyl alcohol directly into... 

Enantioselective Michael addition of glycine derivatives by means of chiral phase-transfer catalysis has been developed to synthesize various functionalized a-alkyl-a-amino acids. Corey utilized 4d as catalyst for asymmetric Michael addition of glycinate Schiff base 1 to a,(3-unsaturated carbonyl substrates with high enantioselectivity (Scheme 2.15) [35,36]. With methyl acrylate as an acceptor, the a-tert-butyl-y-methyl ester of (S)-glutamic acid can be produced, a functionalized glutamic acid... 

Asymmetric epoxidation catalyzed by chiral phase-transfer catalysts is another reaction which has been extensively studied following an initial report by Wynberg [2,44]. Shioiri et al. further improved the enantioselective epoxidation of naphthoquinones under cinchona alkaloid-derived chiral phase-transfer catalysis [45],... 

Verbicky, J.W. and O Neil, E.A. (1985) Chiral phase-transfer catalysis. Enantioselective alkylation of racemic alcohols with a nonfunctionalized optically active phase-transfer catalyst. 

In 1992, O Donnell succeeded in obtaining optically active a-methyl-a-amino acid derivatives 49 in a catalytic manner through the phase-transfer alkylation of p-chlorobenzaldehyde imine of alanine tert-butyl ester 48 with cinchonine-derived la as catalyst (see Scheme 4.16) [46]. Although the enantioselectivities are moderate, this study is the first example of preparing optically active a,a-dialkyl-a-amino acids by chiral phase-transfer catalysis. 

Enantioselective Michael addition of glycine derivatives by means of chiral phase-transfer catalysis has been developed to synthesize various functionalized a-alkyl-amino acids. Corey and colleagues utilized 30d as a catalyst for the asymmetric... 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

Chiral phase-transfer catalysis (PTC) is a very interesting methodology that typically requires simple experimental operations, a mild reaction conditions and inexpensive and/or environmentally benign reagents, and which is amenable to large-scale preparations [15]. The possibihty of developing recoverable and recyclable chiral catalysts has attracted the interest of many groups. Indeed, the immobilization of chiral phase-transfer catalysts has provided the first demonstrations of the feasibility of this approach. 

Dolling, U. H., D. L. Hughes, A. Bhattacharya, K. M. Ryan, S. Karady, L. M. Weinstock, V. J. Grenda, and E. J. J. Grabowski, Efficient Asymmetric Alkylations via Chiral Phase-Transfer Catalysis Applications and Mechanism, Phase-Transfer Cctalysis New Chemistry, Catalysts, and AppUcatwns, C. M. Starks, ed., ACS... 

Chiral ion pairs (B, Fig. 2.2) can be formed by deprotonation of the pronucleophile with a chiral Brpnsted base or employing an achiral base and a chiral phase-transfer catalyst. Chiral phase-transfer catalysis (PTC) [8] illustrates how ion pairing interactions can be used to carry out the enantioface discrimination in conjugate addition reactions. In both cases, the chiral cation is responsible for... 

I.3.I. Chiral Phase-Transfer Catalysis The exploration of modified cinchona alkaloid organocatalysts for asymmetric synthesis indicates that the quaternary ammonium salt derived from cinchona alkaloids is one of the best catalysts in the asymmetric Michael reaction. In 2000, Perrard and co-workers used A/-meth-ylanthracenylquininium (or quinidinium) chloride salt (Q-a or QD-a) for catalyzing the asymmetric Michael addition of dimethyl malonate to 2-pentyl-2-cyclo-penten-l-one (Scheme 9.6). ... 

Moreover, an emerging area in the PTC sector deals with chiral phase-transfer catalysis mediated by phosphonium derivatives. This topic, which was mostly limited to quaternaiy ammonium salts, has been recently reviewed by Enders and Nguyen that described several examples of phosphonium salts as chiral phase transfer catalysts. ... 

In contrast the progress of asymmetric synthesis by use of chiral non-racemic phase transfer catalysts had been slow compared to the ordinary phase transfer catalysis. However, recent achievements in this particular area are noteworthy and efficient asymmetric phase transfer catalysis has been increasingly explored.17 101... 

Asymmetric a-hydroxylation of ketones 97 through phase transfer catalysis under alkaline conditions was realized by use of the Merck catalyst 7 (R=4-CF3, X=Br)[721 as well as the chiral azacrown ether 98[731 in conjunction with molecular oxygen, as shown in Scheme 30. The highest enantioselectivity of 79% ee was attained in the a-hydroxylation of the tetralone 100 by use of the Merck cata-... 

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. 

Figure 11.5. Representative example of the mechanistic pathway of phase transfer catalysis (PTC). (Z, Z — functional group M = metal Q = chiral catalyst R = alkyl or aryl reagent X = halogen).

In particular, it is not only the cinchona alkaloids that are suitable chiral sources for asymmetric organocatalysis [6], but also the corresponding ammonium salts. Indeed, the latter are particularly useful for chiral PTCs because (1) both pseudo enantiomers of the starting amines are inexpensive and available commercially (2) various quaternary ammonium salts can be easily prepared by the use of alkyl halides in a single step and (3) the olefin and hydroxyl functions are beneficial for further modification of the catalyst. In this chapter, the details of recent progress on asymmetric phase-transfer catalysis are described, with special focus on cinchona-derived ammonium salts, except for asymmetric alkylation in a-amino acid synthesis. 

The phase-transfer benzylation of 2 with the catalyst (S)-12a having [1-naphthyl group on the 3,3 -position of the flexible biphenyl moiety proceeded smoothly at 0 °C to afford the corresponding alkylation product (R)-3 in 85% yield with 87% ee after 18 h. The origin of the observed chiral efficiency could be ascribed to the considerable difference in catalytic activity between the rapidly equilibrated, diaste-reomerichomo- and heterochiral catalysts namely, homochiral (S,S)-12a is primarily responsible for the efficient asymmetric phase-transfer catalysis to produce 3 with high enantiomeric excess, whereas the heterochiral (R,S)-12a displays low reactivity and stereoselectivity. 

Neutral cyclodextrins have been used as chiral phase-transfer catalysts for an interesting inverse phase-transfer catalysis reaction [50]. The Markovnikovhydration of the double bond by an oxymercuration-demercuration reaction has been demonstrated in the presence of cyclodextrins as chiral phase-transfer catalysts to obtain products in low to moderate enantioselectivity (Scheme 7.16). The mercuric salts are water-soluble, and remain in the aqueous phase, whereas the neutral alkenes prefer an organic phase. A neutral cyclodextrin helps to bring the alkenes into the aqueous phase in a biphasic reaction, and also provides the necessary asymmetric environment. 

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. 

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