Derived Chiral Phase-Transfer Catalysts for Amino Acid Synthesis

Cinchona-Derived Chiral Phase-Transfer Catalysts for Amino Acid Synthesis... 

The asymmetric synthesis of a-alkyl-a-amino acids using a chiral catalyst is a useful method for the preparation of both natural and unnatural amino acids. O Donnell et al. developed the cinchona alkaloid-catalyzed alkylation of glycine derivatives [49]. However, almost all of the chiral phase-transfer catalysts were restricted to cinchona alkaloid derivatives. In 1999, Maruoka and co-workers designed a chiral ammonium salt bearing a binaphthyl backbone as a chiral phase-transfer catalyst (10a) (Figure 10.11), and demonstrated its catalytic activity... 

Shibasaki developed a library of more than 40 chiral phase-transfer catalysts readily derived from tartaric acid [75]. Catalyst 91 proved optimal and provides access to -amino acids in high optical purities (Scheme 10.14) [75]. For example, alkylation of 78 with bromide 90 in the presence of 91 provided 92 in 80% yield and 88% ee this compound was subsequently employed in the synthesis of the serine protease inhibitor aeruginosin 298-A (93) [76]. 

Some chiral phase-transfer catalysts can also promote enantioselective aldol and Mannich condensations of glycine imine donors with aldehyde and imine acceptors. These reactions provide important tools for the asymmetric constmction of P-hydroxy-a-amino acid and a,p-diamino acid derivatives, which are extremely interesting chiral units in the synthesis of pharmaceutical and natural products. For... 

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 use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

The synthesis of the chiral copper catalyst is very easy to reproduce. The complex catalyses the asymmetric alkylation of enolates of a range of amino acids, thus allowing the synthesis of enantiomeric ally enriched a,a disubstituted amino acids with up to 92% ee. The procedure combines the synthetic simplicity of the Phase Transfer Catalyst (PTC) approach, with the advantages of catalysis by metal complexes. The chemistry is compatible with the use of methyl ester substrates, thus avoiding the use of iso-propyl or ferf-butyl esters which are needed for cinchona-alkaloid catalyzed reactions[4], where the steric bulk of the ester is important for efficient asymmetric induction. Another advantage compared with cinchona-alkaloid systems is that copper(II)(chsalen) catalyses the alkylation of substrates derived from a range of amino acids, not just glycine and alanine (Table 2.4). 

These are potent phase transfer organocatalysts for asymmetric a-alkylation of A/-arylideneglycine fert-butyl ester derivatives for the synthesis of chiral a-substituted a-amino acids at extremely low concentrations of catalyst [Ooi et al. Tetrahedron Asymm 17 603 2006],... 

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