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Updated: May 24, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Copper-mediated difluoromethylation of aryl and vinyl iodides
Patrick S Fier1, John F Hartwig
1Department of Chemistry, University of California, Berkeley, California 94720, United States.
Abstract:
Selectively fluorinated molecules are important as materials, pharmaceuticals, and agrochemicals, but their synthesis by simple, mild, laboratory methods is challenging. We report a straightforward method for the cross-coupling of aryl and vinyl iodides with a difluoromethyl group generated from readily available reagents to form difluoromethylarenes and difluoromethyl-substituted alkenes. The reaction of electron-neutral, electron-rich, and sterically hindered aryl and vinyl iodides with the combination of CuI, CsF and TMSCF(2)H leads to the formation of difluoromethyl-substituted products in high yield with good functional group compatibility. This transformation is surprising, in part, because of the prior observation of the instability of CuCF(2)H.
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