Diversifying fluoroalkanes: light-driven fluoroalkyl transfer via vinylboronate esters

Abstract

We outline a new synthetic strategy to prepare tertiary difluoromethylene-containing molecules from fluoroalkane precursors and vinyl-pinacol boronic ester (vinyl-BPin) reagents. Under irradiation, fluoroalkyl(vinyl)pinacol boronate esters [vinyl-BPin-CF₂R]⁻ undergo a conjugate radical addition process to form new C–C bonds, which does not require air-free conditions and tolerates oxygen and nitrogen-containing heterocycles as well as many classical functional groups. We demonstrate the versatility of this method through a one-pot synthetic protocol using RCF₂H precursors and vinyl-BPin reagents in the presence of a Brønsted base. Widely available fluoroalkanes (HFC-23 and HFC-32) and difluoromethyl heteroarenes are used in this protocol, representing distinct strategies to generate tertiary –CF₂H, –CF₃ and –CF₂-heteroarene molecules. Experimental and theoretical mechanistic investigations reveal a reaction sequence involving radical initiation followed by an ionic 1,2-boronate rearrangement.