Iron-Catalyzed Halogen Exchange of Trifluoromethyl Arenes*

Abstract

The facile production of ArCF₂ X and ArCX₃ from ArCF₃ using catalytic iron(III)halides is reported, which constitutes the first iron-catalyzed halogen exchange for non-aromatic C-F bonds. Theoretical calculations suggest direct activation of C-F bonds by iron coordination. ArCX₃ and ArCF₂ X products of the reaction are synthetically valuable due to their diversification potential. In particular, chloro- and bromodifluoromethyl arenes (ArCF₂ Cl, ArCF₂ Br respectively) provide access to a myriad of difluoromethyl arene derivatives (ArCF₂ 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. These methods are highly practical, being run at convenient temperatures and using inexpensive common reagents.

Keywords: C−F activation; defluorination; halogen exchange; iron catalysis; late-stage modification.