Facile access to difluoromethylene-linked strained aliphatic rings from 2-(difluoromethylene)cyclobutyl sulfonium salts (CB-DFAS) and [1.1.1]propellane

Abstract

A chemodivergent platform that delivers three unprecedented, difluoromethylene (CF₂)-bridged strained scaffolds from 2-(difluoromethylene)cyclobutyl sulfonium salts (CB-DFASs) and [1.1.1]propellane (TCP) has been developed. Simply by modulating the reaction conditions, the combination of TCP, CB-DFASs, and organozinc reagents in the presence of a CuBr catalyst can generate bicyclo[1.1.1]pentane and cyclobutene–CF₂ hybrids. The mild and operationally convenient protocol provides medicinal chemists with facile access to previously unreachable chemical space.