Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI
He Liu, Jian Wu, Yuxuan Jin, Xuebing Leng, Qilong Shen
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.