Diastereo‐ and Enantioselective Reductive Mannich‐type Reaction of α,β‐Unsaturated Carboxylic Acids to Ketimines: A Direct Entry to Unprotected β^2,3,3‐Amino Acids

Abstract

Stereoselective construction of unprotected βamino acids is a significant challenge owing to the lack of methods for the catalytic generation of highly enantioenriched carboxylic acid enolates. In this study, a novel coppercatalyzed diastereo-and enantioselective reductive Mannichtype reaction of α,β-unsaturated carboxylic acids was developed, which provides a direct and scalable synthetic method for enantioenriched β 2,3,3 -amino acids with vicinal stereogenic centers. The protocol features in situ generation of transiently protected carboxylic acids by a hydrosilane and their diastereo-and enantioselective reductive coupling with ketimines. The synthetic utility of this process was demonstrated by a gram-scale reaction and the transformation of βamino acids.