Iron-Catalyzed Halogen Exchange of Trifluoromethyl Arenes
We report the facile production of ArCF<sub>2</sub>X and ArCX<sub>3 </sub>from ArCF<sub>3</sub> 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. ArCX<sub>3</sub> and ArCF<sub>2</sub>X products of the reaction are synthetically valuable due to their diversification potential. In particular, bromo-, chloro-, and iododifluoromethyl arenes (ArCF<sub>2</sub>Br, ArCF<sub>2</sub>Cl, ArCF<sub>2</sub>I, respectively) provide access to a myriad of difluoromethyl arene derivatives (ArCF<sub>2</sub>R). 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.