Catalytic asymmetric Strecker synthesis. Preparation of enantiomerically pure alpha-amino acid derivatives from aldimines and tributyltin cyanide or achiral aldehydes, amines, and hydrogen cyanide using a chiral zirconium catalyst

Catalytic enantioselective Stocker-type reactions of aldimines with tributy ltin cyanide (Bu3SnCN) proceeded smoothly in the presence of a novel chiral zirconium catalyst. High levels of enantioselectivities in the synthesis o f alpha-amino nitrile derivatives with wide substrate generality were obtai ned via these reactions. In addition, hydrogen cyanide (HCN) was successful ly used instead of Bu3SnCN as the cyanide source. Catalytic asymmetric Stre cker amino acid synthesis starting from achiral aldehydes, amines, and HCN using a chiral zirconium catalyst has also been achieved. The three-compone nt asymmetric process reported here significantly improves upon the origina l Stocker reaction, and has advantages over previous reactions using unstab le imines (Schiff bases) as starting materials. Moreover, high yields and e nantioselectivities have been obtained even in the reactions using aliphati c aldehydes, and both enantiomers of various types of alpha-amino acid deri vatives can be prepared. As demonstrations to show the utility of this reac tion, efficient syntheses of homophenylalanine, leucine amide, and pipecoli c acid derivatives have been performed. Finally, two novel binuclear zircon ium complexes (3 and 4) are postulated to be active chiral catalysts in the reactions of aldimines with Bu3SnCN and the three-component reactions, res pectively, and low loading levels of the chiral catalysts (1-2.5 mol %) hav e been accomplished in both cases.