Diverse Synthesis of Chiral Trifluoromethylated Alkanes via Nickel-Catalyzed Enantioconvergent Reductive Hydroalkylation of Unactivated Olefins

Here, we report a nickel-catalyzed enantioconvergent hydroalkylation of olefins with trifluoromethyl-containing alpha-alkyl halides for the synthesis of enantioenriched trifluoromethylated alkanes. This reaction employs readily available and bench-stable alkenes as alkyl coupling partners, featuring mild conditions, a broad substrate scope, and high functional group tolerance. The synthetic utility of this method is further demonstrated in the late-stage functionalization of a range of drug molecules and natural products.

Automated summary

In this study, a nickel-catalyzed enantioconvergent hydroalkylation method has been developed for the synthesis of enantioenriched trifluoromethylated alkanes. The reaction utilizes readily available alkenes as alkyl coupling partners and offers mild conditions, a broad substrate scope, and high functional group tolerance. The synthetic utility of this method has been demonstrated through the late-stage functionalization of various drug molecules and natural products.