Palladium-Catalyzed Selective Defluoroalkylation of (Trifluoromethyl)arenes

Abstract The selective functionalization of C–F bonds in trifluoromethylated arenes (ArCF3) is essential due to the extensive use of fluorinated compounds in pharmaceuticals, agrochemicals, and materials science, alongside emerging regulatory restrictions on trifluoromethyl groups. Here, we report a hybrid palladium-catalyzed strategy for the selective defluorination and functionalization of ArCF3, featuring intermolecular carboamination of linear conjugated dienes or defluorinative cross-coupling with nonactivated alkenes. This methodology enables the 1,4-addition of dienes with exclusive E-selectivity or the defluoroalkylation of (trifluoromethyl)arenes, providing efficient routes to difluoromethylated compounds and addressing key challenges in synthetic fluorine chemistry.