Catalytic Asymmetric Hydroalkylation of α,β-Unsaturated Amides Enabled by Regio-Reversed and Enantiodifferentiating syn-Hydronickellation

Here, we report an enantioselective nickel-hydride catalyzed hydroalkylation of readily accessible beta-alkyl-alpha,beta-unsaturated amides to form structurally diverse beta-chiral amides. This process was proposed to proceed through an enantiodifferentiating syn-hydrometalation of nickel hydride, forming chiral alkylnickel at the beta-position in which the regioselectivity is different from that with copper hydride. This regio-reversed hydronickellation process provides a complementary approach to access enantioenriched beta-functionalization amides with a stereocenter at the beta-position.

Automated summary

Here, a chiral selective nickel-hydride catalyzed hydroalkylation method is reported for the synthesis of structurally diverse beta-chiral amides from readily accessible beta-alkyl-alpha,beta-unsaturated amides. The regio-reversed hydronickellation process provides a complementary approach to access enantioenriched beta-functionalization amides with a stereocenter at the beta-position.