Catalytic Asymmetric Strecker Synthesis. Preparation of Enantiomerically Pure α-Amino Acid Derivatives from Aldimines and Tributyltin Cyanide or Achiral Aldehydes, Amines, and Hydrogen Cyanide Using a Chiral Zirconium Catalyst

Abstract

Catalytic enantioselective Strecker-type reactions of aldimines with tributyltin cyanide (Bu3SnCN) proceeded smoothly in the presence of a novel chiral zirconium catalyst. High levels of enantioselectivities in the synthesis of α-amino nitrile derivatives with wide substrate generality were obtained via these reactions. In addition, hydrogen cyanide (HCN) was successfully used instead of Bu3SnCN as the cyanide source. Catalytic asymmetric Strecker amino acid synthesis starting from achiral aldehydes, amines, and HCN using a chiral zirconium catalyst has also been achieved. The three-component asymmetric process reported here significantly improves upon the original Strecker reaction, and has advantages over previous reactions using unstable imines (Schiff bases) as starting materials. Moreover, high yields and enantioselectivities have been obtained even in the reactions using aliphatic aldehydes, and both enantiomers of various types of α-amino acid derivatives can be prepared. As demonstrations to show the utility of this reaction, efficient syntheses of homophenylalanine, leucine amide, and pipecolic acid derivatives have been performed. Finally, two novel binuclear zirconium complexes (3 and 4) are postulated to be active chiral catalysts in the reactions of aldimines with Bu3SnCN and the three-component reactions, respectively, and low loading levels of the chiral catalysts (1−2.5 mol %) have been accomplished in both cases.