Iron‐Catalyzed Halogen Exchange of Trifluoromethyl Arenes**
Andreas Dorian, Emily Landgreen, Hayley Petras, James J. Shepherd, Florence Williams
Abstract
Abstract The facile production of ArCF 2 X and ArCX 3 from ArCF 3 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. ArCX 3 and ArCF 2 X products of the reaction are synthetically valuable due to their diversification potential. In particular, chloro‐ and bromodifluoromethyl arenes (ArCF 2 Cl, ArCF 2 Br respectively) provide access to a myriad of difluoromethyl arene derivatives (ArCF 2 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.