Iron-Catalyzed Halogen Exchange of Trifluoromethyl Arenes

We report the facile production of ArCF₂X and ArCX₃ from ArCF₃ using catalytic iron(III)halides, which constitutes the first iron-catalyzed halogen exchange for non-aromatic CF bonds. Theoretical calculations suggest direct activation of C–F bonds by iron coordination. ArCX₃ and ArCF₂X products of the reaction are synthetically valuable due to their diversification potential. In particular, bromo-, chloro-, and iododifluoromethyl arenes (ArCF₂Br, ArCF₂Cl, ArCF₂I, respectively) provide access to a myriad of difluoromethyl arene derivatives (ArCF₂R). To optimize for mono-halogen exchange, a statistical method called Design of Experiments was used. Optimized parameters were successfully applied to electron rich and electron deficient aromatic substrates, and to the late stage diversification of flufenoxuron, a commercial insecticide.