Asymmetric aldol reactions of chiral Ni(II)-complex of glycine with aliphatic aldehydes. Stereodivergent synthesis of syn-(2S)- and syn-(2R)-β-alkylserines

Abstract

Stereoselectivity of aldol reactions between aliphatic aldehydes and Ni(II)-complex of chiral non-racemic Schiff base of glycine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone (BPB) in the presence of excess of MeONa, has been studied as a function of time, reaction conditions and nature of an aldehyde. Two salient features of the reaction, very high pseudokinetic syn-(2S)-diastereoselectivity, and dependence of thermodynamic syn-(2R)-diastereoselectivity on the steric bulk of an aldehyde side chain, were disclosed and used for efficient (more than 90% de and ee) asymmetric synthesis of both syn-(2S) and syn-(2R)-3-alkyl substituted serines. Synthetic potential and reliability of this asymmetric method are demonstrated with the large scale (2–20 g) preparation of enantiomerically pure amino acids.