C ^α -Umpolung of Amides Strategy for Enantioselective Propargylic Amination toward C ^α -Tetrasubstituted α-Amino Acid Derivatives

A strategy for the C^α-umpolung of amides through the copper-catalyzed decarboxylation of 5-ethynyloxazolidine-2,4-diones was developed. Building on this, an asymmetric propargylic amination was achieved using primary and secondary amines as nucleophiles under cooperative catalysis of a chiral copper complex and a quinidine-derived bifunctional organocatalyst, affording a range of C^α-tetrasubstituted α-amino acid derivatives in high yields with excellent enantioselectivities. The synthetic utility of this protocol was demonstrated by late-stage modification of pharmaceuticals, large-scale reactions, and versatile derivatization of products.