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- W2901414930 abstract "Abstract The selective incorporation of gem -difluoroalkyl groups into biologically active molecules has long been used as an efficient strategy for drug design and discovery. However, the catalytic C(sp 3 )-CF 2 bond-forming cross-coupling reaction for selective incorporation of difluoromethylene group into diverse alkyl chains, especially more sterically demanding secondary and tertiary functionalized alkanes, still remains as a major challenge. Herein, we describe a cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides, which exhibited high efficiency, broad scope and mild conditions. The synthetic utility of this method is demonstrated by late-stage difluoroalkylation of donepezil, a well-known acetylcholinesterase inhibitor used to treat the Alzheimer’s disease. Preliminary mechanistic investigations indicate that a difluoroalkyl radical is involved in a Co(I)/Co(III) catalytic cycle. This cobalt-catalyzed fluoroalkylation thus offers insights into an efficient way for the synthesis of fluoroalkylated bioactive molecules for drug discovery." @default.
- W2901414930 created "2018-11-29" @default.
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- W2901414930 date "2018-11-23" @default.
- W2901414930 modified "2023-10-11" @default.
- W2901414930 title "Cobalt-catalyzed difluoroalkylation of tertiary aryl ketones for facile synthesis of quaternary alkyl difluorides" @default.
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- W2901414930 doi "https://doi.org/10.1038/s41467-018-07525-y" @default.
- W2901414930 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6251884" @default.
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