Catalytic Asymmetric Homologation of 4-Substituted Cyclohexanones with CF3CHN2: Enantioselective Synthesis of α-Trifluoromethyl Cycloheptanones

Introduction of the trifluoromethyl group (CF3) into organic molecules in an enantioselective manner has attracted significant attention, but still remains a challenging problem. We herein report a catalytic asymmetric trifluoromethylation of cyclic ketones via a Sc-III/chiral bisoxazoline-catalyzed homologation reaction by employing 2,2,2-trifluorodiazoethane (CF3CHN2) as the CF3 source. This desymmetrization process is highly efficient and generates two chiral centers with excellent diastereoselectivity and enantioselectivity, affording chiral alpha-trifluoromethyl cyclic ketones in a straightforward manner.

Automated summary

The catalytic asymmetric trifluoromethylation of cyclic ketones via a Sc-III/chiral bisoxazoline-catalyzed homologation reaction using 2,2,2-trifluorodiazoethane (CF3CHN2) as the CF3 source is an efficient method to generate chiral alpha-trifluoromethyl cyclic ketones with excellent diastereoselectivity and enantioselectivity.