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Iron‐Catalyzed Halogen Exchange of Trifluoromethyl Arenes **
Author(s) -
Dorian Andreas,
Landgreen Emily J.,
Petras Hayley R.,
Shepherd James J.,
Williams Florence J.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101324
Subject(s) - halogen , catalysis , chemistry , reagent , halide , trifluoromethyl , combinatorial chemistry , medicinal chemistry , organic chemistry , alkyl
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.