Chem Catalysis
Volume 2, Issue 7, 21 July 2022, Pages 1793-1806
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Article
Photocatalytic fluoroalkylations of (hetero)arenes enabled by the acid-triggered reactivity umpolung of acetoxime esters

https://doi.org/10.1016/j.checat.2022.05.018Get rights and content
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Highlights

  • The unprecedented acid-triggered reactivity umpolung of acetoxime ester

  • Photocatalytic method for C–H fluoroalkylation of (hetero)arenes and olefines

  • Inexpensive and easily available fluoroalkyl carboxylic anhydrides

  • Simple acetoxime as an efficient activator to fluoroalkyl carboxylic anhydrides

The bigger picture

Over the past decades, considerable efforts have been devoted toward exploring readily available trifluoroacetic acid or its anhydride as a CF3 source for trifluoromethylation reactions. Herein, a general photocatalytic method was developed for fluoroalkylation of arenes and aromatic heterocycles with fluoroalkyl carboxylic anhydrides using simple acetoxime as the activator. The established conditions were also applicable to oxytrifluoromethylation and intramolecular carbotrifluoromethylation of alkenes, and the modification of biologically active molecules and gram-scale synthesis further highlighted its potential utility. Compared with the fact that single-electron transfer (SET) reduction of oxime trifluoroacetate esters generates preferentially iminyl radical and stable trifluoroacetate anions, our work discovered the unprecedented acid-triggered reactivity umpolung of acetoxime ester toward delivering a CF3 radical.

Summary

The importance of trifluoromethyl (CF3) group-containing compounds in pharmaceuticals, agrochemicals, and materials has spurred tremendous efforts devoted to the development of methods for incorporation of the trifluoromethyl group into molecular frameworks and discoveries of trifluoromethylating reagents. In this paper, we report a general photocatalytic method for regioselective C–H fluoroalkylation of (hetero)arenes and olefines that uses readily available fluoroalkyl carboxylic anhydrides as fluoroalkylating reagents in the presence of simple acetoxime as an activator. The success achieved in the development of such a photocatalytic C–H fluoroalkylation method is attributed to discovery of the unprecedented acid-triggered reactivity umpolung of acetoxime ester toward single-electron reduction-induced cleavage of N–O σ bond. Such a new reactivity mode of oxime esters will stimulate efforts to expand the synthetic applications of readily available oxime esters.

Keywords

photoredox catalysis
fluoroalkylation
radical
trifluoroacetic anhydride
acetoxime

UN sustainable development goals

SDG3: Good health and well-being

Data and code availability

Data relating to the materials and methods, experimental procedures, nuclear magnetic resonance (NMR) spectra, and analytical data of the compounds generated in this study are provided in the supplemental information.

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