Asymmetric [2+1] cycloaddition of difluoroalkyl-substituted carbenes with alkenes under rhodium catalysis: Synthesis of chiral difluoroalkyl-substituted cyclopropanes.

Abstract

Herein, we report a novel strategy for the synthesis of chiral difluoroalkyl-substituted cyclopropanes through enantioselective [2+ 1] cyclopropanation of alkenes and difluoroalkyl-substituted carbenes under rhodium catalysis, wherein the newly designed α, α-difluoro-β-carbonyl ketone N-triftosylhydrazones are used as the difluoroalkyl-substituted carbenes precursors. This approach represents the first asymmetric cyclopropanation of alkenes with difluoroalkyl carbenes, featuring high yield, high enantioselectivity, and broad substrate scope. Gram-scale synthesis and further interconversion of diverse functional groups demonstrate the usefulness of this protocol in the preparation of diverse functionalized chiral difluoroalkyl-substituted cyclopropanes.