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Cobalt-catalyzed decarboxylative difluoroalkylation of nitrophenylacetic acid salts
Tunge, Jon A. Smith, Ian Joseph, Ebbin
Tunge, Jon A.
Smith, Ian
Joseph, Ebbin
Abstract
The selective installation of fluorine-containing groups into biologically relevant molecules has been used as a common strategy for the development of pharmaceutically active molecules. However, the selective incorporation of gem-difluoromethylene groups next to sterically demanding secondary and tertiary alkyl groups remains a challenge. Herein, we report the first cobalt-catalyzed regioselective difluoroalkylation of carboxylic acid salts. The reaction allows for the facile construction of various difluoroalkylated products in good yields tolerating a wide range of functionalities on either reaction partner. The potential of the method is illustrated by the late-stage functionalization of molecules of biological relevance. Mechanistic studies support the in situ formation of a cobalt(i) species and the intermediacy of difluoroalkyl radicals, thus suggesting a Co(i)/Co(ii)/Co(iii) catalytic cycle.
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2023-11-16
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Chemical Science
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Joseph E, Smith I, Tunge JA. Cobalt-catalyzed decarboxylative difluoroalkylation of nitrophenylacetic acid salts. Chem Sci. 2023 Nov 16;14(47):13902-13907. doi: 10.1039/d3sc05583c. PMID: 38075641; PMCID: PMC10699560