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Issue 11, 2019
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Catalytic radical difluoromethoxylation of arenes and heteroarenes

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Abstract

Intermolecular C–H difluoromethoxylation of (hetero)arenes remains a long-standing and unsolved problem in organic synthesis. Herein, we report the first catalytic protocol employing a redox-active difluoromethoxylating reagent 1a and photoredox catalysts for the direct C–H difluoromethoxylation of (hetero)arenes. Our approach is operationally simple, proceeds at room temperature, and uses bench-stable reagents. Its synthetic utility is highlighted by mild reaction conditions that tolerate a wide variety of functional groups and biorelevant molecules. Experimental and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to 1a forming a neutral radical intermediate that liberates the OCF2H radical exclusively. Addition of this radical to (hetero)arenes gives difluoromethoxylated cyclohexadienyl radicals that are oxidized and deprotonated to afford the products of difluoromethoxylation.

Graphical abstract: Catalytic radical difluoromethoxylation of arenes and heteroarenes

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Publication details

The article was received on 03 Dec 2018, accepted on 04 Feb 2019 and first published on 11 Feb 2019


Article type: Edge Article
DOI: 10.1039/C8SC05390A
Chem. Sci., 2019,10, 3217-3222
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Catalytic radical difluoromethoxylation of arenes and heteroarenes

    Johnny W. Lee, W. Zheng, C. A. Morales-Rivera, P. Liu and M. Ngai, Chem. Sci., 2019, 10, 3217
    DOI: 10.1039/C8SC05390A

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