Enantioselective Ni-catalyzed syn-hydrometalative cyclization of alkyne-tethered ketoamides to α-hydroxy-γ-lactams†‡

An enantioselective Ni-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 87.5 : 12.5–97 : 3 er. Synthetic utilities, including scale-up reaction and product derivatization, are also demonstrated. This research presents a regioselective functionalization of alkynes and provides an efficient strategy to access functional group-enriched chiral heterocycles.