Tetrahedron Chem (Jun 2024)

Electrochemical hydrodefluorination of an aromatic trifluoromethyl group with ammonia as the hydrogen source

  • Jie Sheng,
  • Jiaming Cheng,
  • Xu Cheng

Journal volume & issue
Vol. 10
p. 100074

Abstract

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The aromatic difluoromethyl group (Ar-CF2H) is an emerging functional group found in pharmaceutical compounds. For synthesis, the hydrodefluorination of Ar-CF3 molecules is a straightforward approach in terms of atom economy and substrate scope. The reported hydrodefluorination reaction focused on the Ar-CF3 substrate bearing electron-withdrawing groups. In this report, we utilized electricity as the driving force for the hydrodefluorination of ArCF3, which involves electron-donating groups. By using ammonia as a traceless hydrogen and electron donor, the reaction could tolerate a variety of labile groups, including unprotected amine, pyrrole, furan, thioether, and silyl group, without sacrificial anodes in undivided cells. In this work, tBuOLi was found to be an essential additive for achieving good reactivity and chemoselectivity. Several Ar-CF2H pharmaceutical and intermediate products were synthesized via this approach.