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Updated: Jun 6, 2025

Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
Defluorinative thio-functionalization: direct synthesis of methyl-dithioesters from trifluoromethylarenes
Marcus Söderström1, Esther Olaniran Håkansson2, Luke R Odell2
1The Beijer Laboratory, Department of Medicinal Chemistry, Uppsala University, 751 23 Uppsala, Sweden.
Abstract:
A new functional group transformation allowing the synthesis of methyl-dithioesters from readily available trifluoromethyl arenes via defluorinative functionalization has been developed. This microwave-assisted method is operationally simple, rapid, and eliminates the need for pre-functionalization while accommodating a broad range of functional groups. In addition, it does not rely on highly odorous thiol sources, and utilizes the commercially available reagent BF3SMe2 complex as a multifunctional Lewis acid/sulfur source/defluorination and demethylation agent. Finally, this approach is suitable for late-stage functionalizations, as shown by the transformation of pharmaceuticals leflunomide, flufenamic acid and celecoxib into novel methyl-dithioester derivatives.
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