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 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.