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Selective C-H trifluoromethoxylation of (hetero)arenes as limiting reagent.

ABSTRACT: Methods for direct C-H trifluoromethoxylation of arenes and heteroarenes are rare, despite the importance of trifluoromethoxylated compounds for pharmaceuticals, agrochemicals, and material sciences. Especially selective C-H trifluoromethoxylation of pyridines remains a formidable challenge. Here we show a general late-stage C-H trifluoromethoxylation of arenes and heteroarenes as limiting reagent with trifluoromethoxide anion. The reaction is mediated by silver salts under mild reaction conditions, exhibiting broad substrate scope and wide functional-group compatibility. In addition, ortho-position selective C-H trifluoromethoxylation of pyridines is observed. The method is not only applicable to the gram-scale synthesis of trifluoromethoxylated products but also allows efficient late-stage C-H trifluoromethoxylation of marketed small-molecule drugs, common pharmacophores and natural products.

SUBMITTER: Deng Z

PROVIDER: S-EPMC7244481 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Selective C-H trifluoromethoxylation of (hetero)arenes as limiting reagent.

Deng Zhijie Z Zhao Mingxin M Wang Feng F Tang Pingping P

Nature communications 20200522 1

Methods for direct C-H trifluoromethoxylation of arenes and heteroarenes are rare, despite the importance of trifluoromethoxylated compounds for pharmaceuticals, agrochemicals, and material sciences. Especially selective C-H trifluoromethoxylation of pyridines remains a formidable challenge. Here we show a general late-stage C-H trifluoromethoxylation of arenes and heteroarenes as limiting reagent with trifluoromethoxide anion. The reaction is mediated by silver salts under mild reaction conditi ...[more]

PMID: 32444828

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