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

Stereoselective construction of unprotected β -amino acids is a significant challenge owing to the lack of methods for the catalytic generation of highly enantioenriched carboxylic acid enolates. In this study, we developed a novel copper-catalyzed diastereo- and enantioselective reductive Mannich-type reaction of α,β -unsaturated carboxylic acids, which provides a direct and scalable synthetic method for enantioenriched β 2,3,3 -amino acids with vicinal stereogenic centers. Our 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 β -amino acids.