Thiazolylalanine-Derived Catalysts for Enantioselective Intermolecular Aldehyde−Imine Cross-Couplings

Catalytic asymmetric cross-coupling reactions between aldehydes and N-acylimines have been discovered that employ thiazolylalanine derivatives as catalysts.

Abstract

Catalytic asymmetric cross-coupling reactions between aldehydes and N-acylimines have been discovered that employ thiazolylalanine derivatives as catalysts. Alkylation of the thiazolyl moiety, followed by in situ generation of the derived thiazolium ylide using a tertiary amine base, leads to the active catalyst. alpha-Amidoketone products are isolated in up to 90% yield with up to 87% enantiomeric excess (>98% ee after a single recrystallization). The use of a hindered base to suppress product racemization was stimulated by a mechanistic study that revealed an isotope effect on the racemization rate of the product.