Enantioselective NiH-Catalyzed Syn-Hydrometalative Cyclization of Alkyne-tethered Ketoamides to α-Hydroxy-γ-Lactams

An enantioselective NiH-catalyzed syn-hydrocyclization of alkyne-tethered ketoamides for the synthesis of α-hydroxy γ-lactams is reported. Using Ni(OTs)2•6H2O/(S,S)-Me-Duphos as a precatalyst and (EtO)2MeSiH as a hydride source, a broad range of enantioenriched γ-lactams with a fully substituted stereogenic center are obtained in 32–84% yields with 89.5:10.5–96.5:3.5 er. Synthetic utilities, including scale-up reaction and product derivatization, are also demonstrated. This research represents a ligand-enabled regioselective functionalization of alkynes and provides an efficient strategy to access functional group-enriched chiral heterocycles.