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Carbodefluorination of fluoroalkyl ketones via a carbene-initiated rearrangement strategy

Author

Listed:
  • Linxuan Li

    (Northeast Normal University)

  • Xinyu Zhang

    (Northeast Normal University)

  • Yongquan Ning

    (Northeast Normal University)

  • Xiaolong Zhang

    (Northeast Normal University)

  • Binbin Liu

    (Northeast Normal University)

  • Zhansong Zhang

    (Northeast Normal University)

  • Paramasivam Sivaguru

    (Northeast Normal University)

  • Giuseppe Zanoni

    (University of Pavia)

  • Shuang Li

    (Northeast Normal University)

  • Edward A. Anderson

    (University of Oxford)

  • Xihe Bi

    (Northeast Normal University
    Nankai University)

Abstract

The C–F bond cleavage and C–C bond formation (i.e., carbodefluorination) of readily accessible (per)fluoroalkyl groups constitutes an atom-economical and efficient route to partially fluorinated compounds. However, the selective mono-carbodefluorination of trifluoromethyl (CF3) groups remains a challenge, due to the notorious inertness of C–F bond and the risk of over-defluorination arising from C–F bond strength decrease as the defluorination proceeds. Herein, we report a carbene-initiated rearrangement strategy for the carbodefluorination of fluoroalkyl ketones with β,γ-unsaturated alcohols to provide skeletally and functionally diverse α-mono- and α,α-difluoro-γ,δ-unsaturated ketones. The reaction starts with the formation of silver carbenes from fluoroalkyl N-triftosylhydrazones, followed by nucleophilic attack of a β,γ-unsaturated alcohol to form key silver-coordinated oxonium ylide intermediates, which triggers selective C–F bond cleavage by HF elimination and C–C bond formation through Claisen rearrangement of in situ generated difluorovinyl ether. The origin of chemoselectivity and the reaction mechanism are determined by experimental and DFT calculations. Collectively, this strategy by an intramolecular cascade process offers significant advances over existing stepwise strategies in terms of selectivity, efficiency, functional group tolerance, etc.

Suggested Citation

  • Linxuan Li & Xinyu Zhang & Yongquan Ning & Xiaolong Zhang & Binbin Liu & Zhansong Zhang & Paramasivam Sivaguru & Giuseppe Zanoni & Shuang Li & Edward A. Anderson & Xihe Bi, 2022. "Carbodefluorination of fluoroalkyl ketones via a carbene-initiated rearrangement strategy," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31976-z
    DOI: 10.1038/s41467-022-31976-z
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    References listed on IDEAS

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    1. Xiao-Si Hu & Jun-Xiong He & Su-Zhen Dong & Qiu-Hua Zhao & Jin-Sheng Yu & Jian Zhou, 2020. "Regioselective Markovnikov hydrodifluoroalkylation of alkenes using difluoroenoxysilanes," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
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