Reductive Catalytic Difluorocarbene Transfer via Palladium Catalysis

Abstract

A palladium-catalyzed reductive difluorocarbene transfer reaction that tames difluorocarbene to couple with two electrophiles has been developed, representing a new mode of difluorocarbene transfer reaction. The approach uses low-cost and bulk industrial chemical chlorodifluoromethane (ClCF₂ H) as the difluorocarbene precursor. It produces a variety of difluoromethylated (hetero)arenes from widely available aryl halides/triflates and proton sources, featuring high functional group tolerance and synthetic convenience without preparing organometallic reagents. Experimental mechanistic studies reveal that an unexpected Pd^0/II catalytic cycle is involved in this reductive reaction, wherein the oxidative addition of palladium(0) difluorocarbene ([Pd⁰ (L_n )]=CF₂ ) with aryl electrophile to generate the key intermediate aryldifluoromethylpalladium [ArCF₂ Pd(L_n )X], followed by reaction with hydroquinone, is responsible for the reductive difluorocarbene transfer.

Keywords: Aryl Bromide; ClCF2H; Difluoromethylation; Palladium Difluorocarbene; Reductive Difluorocarbene Transfer.