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 & alpha;-hydroxy & gamma;-lactams is reported. Using Ni(OTs)(2)& BULL;6H(2)O/(S,S)-Me-Duphos as a precatalyst and (EtO)(2)MeSiH as a hydride source, a broad range of enantioenriched & gamma;-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.

Automated summary

An enantioselective Ni-catalyzed syn-hydrocyclization reaction was developed for the synthesis of α-hydroxy γ-lactams. By using Ni(OTs)(2)·6H(2)O/(S,S)-Me-Duphos as a precatalyst and (EtO)2MeSiH as a hydride source, a wide range of enantioenriched γ-lactams with fully substituted stereogenic centers were obtained in 32-84% yields with 87.5:12.5-97:3 er. This research provides a regioselective functionalization of alkynes and offers an efficient strategy for accessing functional group-enriched chiral heterocycles.