Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI

Abstract

The synthesis, characterization, and reactivity of key intermediates [Cu(CF₃)(X)]^-Q⁺ (X = CF₃ or I, Q = PPh₄) in copper-mediated trifluoromethylation of aryl halides were studied. Qualitative and quantitative studies showed [Cu(CF₃)₂]^-Q⁺ and [Cu(CF₃)(I)]^-Q⁺ were not highly reactive. Instead, a much more reactive species, ligandless [CuCF₃] or DMF-ligated species [(DMF)CuCF₃], was generated in the presence of excess CuI. On the basis of these results, a general mechanistic map for CuI-promoted trifluoromethylation of aryl halides was proposed. Furthermore, on the basis of this mechanistic understanding, a HOAc-promoted protocol for trifluoromethylation of aryl halides with [Ph₄P]⁺[Cu(CF₃)₂]^- was developed.