Issue 11, 2019

Catalytic radical difluoromethoxylation of arenes and heteroarenes


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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Article information

Article type
Edge Article
03 Dec 2018
04 Feb 2019
First published
11 Feb 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 3217-3222

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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