Dearomatization Approach to 2-Trifluoromethylated Benzofuran and Dihydrobenzofuran Products
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Updated: Feb 28, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
David T Smith1, Edon Vitaku1, Jon T Njardarson1
1Department of Chemistry and Biochemistry, University of Arizona , 1306 East University Boulevard, Tucson, Arizona 85721, United States.
Abstract:
A mild dearomatization enabled ortho-selective replacement of an aromatic C-H bond with a hexafluoroacetylacetone (hfacac) substituent has been developed. This reaction is dependent on a hypervalent iodine generated phenoxonium intermediate, a critical choice of solvent, and reagent addition order. The fluorinated dihydrobenzofuran product can be transformed into dihydrobenzofuran and benzofuran products decorated with a 2-trifluoromethyl group. The 3-trifluoromethylacyl substituted benzofurans rapidly form hydrates, which can be reduced to the corresponding alcohols.
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