Nickel-Mediated Trifluoromethylation of Phenol Derivatives by Aryl C-O Bond Activation
Wei-Qiang Hu1, Shen Pan1, Xiu-Hua Xu1
1Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Science, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai, 200032, China.
Abstract:
The increasing pharmaceutical importance of trifluoromethylarenes has stimulated the development of more efficient trifluoromethylation reactions. Tremendous efforts have focused on copper- and palladium-mediated/catalyzed trifluoromethylation of aryl halides. In contrast, no general method exists for the conversion of widely available inert electrophiles, such as phenol derivatives, into the corresponding trifluoromethylated arenes. Reported herein is a practical nickel-mediated trifluoromethylation of phenol derivatives with readily available trimethyl(trifluoromethyl)silane (TMSCF3 ). The strategy relies on PMe3 -promoted oxidative addition and transmetalation, and CCl3 CN-induced reductive elimination. The broad utility of this transformation has been demonstrated through the direct incorporation of trifluoromethyl into aromatic and heteroaromatic systems, including biorelevant compounds.
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