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Updated: Apr 21, 2026

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Diversity-oriented approach to CF3CHF-, CF3CFBr-, CF3CF2-, (CF3)2CH-, and CF3(SCF3)CH-substituted arenes from
Enrico Emer1, Jack Twilton, Matthew Tredwell
1Chemistry Research Laboratory, University of Oxford , 12 Mansfield Road, OX1 3TA Oxford, U.K.
Abstract:
Arenes substituted with perfluoroalkyl groups are attractive targets for drug and agrochemical development. Exploiting the carbenic character of donor/acceptor diazo compounds, a diversity-oriented synthesis of perfluoroalkylated arenes, for late stage fluorofunctionalization, is described. The reaction of 1-(diazo-2,2,2-trifluoroethyl)arenes with HF, F/Br, F2, CF3H, and CF3SH sources give direct access to a variety of perfluoroalkyl-substituted arenes presenting with incremental fluorine content. The value of this approach is also demonstrated for radiochemistry and positron emission tomography with the [(18)F]-labeling of CF3CHF-, CF3CBrF-, and CF3CF2-arenes from [(18)F]fluoride.
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