Synthesis of difluoromethyl carbinols from the Friedel–Crafts reaction of electron-rich arenes with difluorovinyl arylsulfonates

Abstract

α,α-Difluoromethyl carbinols are important structural motifs in many therapeutic agents and functional materials. Herein, we developed a sustainable and efficient method for the synthesis of a series of α,α-difluoromethyl carbinols from the remarkable Friedel–Crafts reaction of electron-rich arenes including indoles, phenols and anilines with easily accessible 2,2-difluorovinyl arylsulfonates in trifluoroethanol. This simple and straightforward protocol takes advantage of the readily accessible difluoroacetaldehyde in situ from 2,2-difluorovinyl arylsulfonate in a step-economical manner. Meanwhile, this transformation is distinguished by its wide substrate scope and excellent functional group tolerance. Preliminary mechanistic studies suggest that trifluoroethanol is crucial to this reaction.