Ni-Catalyzed Enantioselective C-Acylation of α-Substituted Lactams

A new strategy for catalytic enantioselective C-acylation to generate alpha-quaternary-substituted lactams is reported. Ni-catalyzed three-component coupling of lactam enolates, benzonitriles, and aryl halides produces beta-imino lactams that then afford beta-keto lactams by acid hydrolysis. Use of a readily available Mandyphos-type ligand and addition of LiBr enable the construction of quaternary stereocenters on alpha-substituted lactams to form beta-keto lactams in up to 94% ee.