Pd-Catalyzed Divergent Site-Selective Difluoromethylation and Difluoromethylcarbonylation of Aryl Sulfonium Salts

The incorporation of the difluoromethyl (CF2H) group into arenes has increasingly been recognized as important in drug discovery. Herein, we report a divergent cross-coupling method for constructing both aryl difluoromethanes and aryl difluoroketones from aryl thianthrenium salts. Site selectivity for Negishi-type coupling and C1 insertion reactions was achieved under palladium catalysis. Both transformations proceed with broad functional group tolerance, enabling the late-stage difluoromethylation and difluoromethylcarbonylation of complex drug molecules. The synthetic utility of this method has been demonstrated by synthesizing four pharmaceutical analogues from the same precursor and applying it in the downstream functionalization of difluoroketones.