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Precise electro-reduction of alkyl halides for radical defluorinative alkylation

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Abstract

Reported here is a precise electro-reduction strategy for radical defluorinative alkylation towards the synthesis of gem-difluoroalkenes from α-trifluoromethylstyrenes. According to the redox-potential difference of the radical precursors, direct or indirect electrolysis is respectively adopted to realize the precise reduction. An easy-to-handle, catalyst- and metal-free condition is developed for the reduction of alkyl radical precursors that are generally easier to be reduced than α-trifluoromethylstyrenes, while a novel electro-Ni-catalytic system is established for the electro-reduction of alkyl bromides or chlorides towards the electrochemical synthesis of gem-difluoroalkenes. The merit of this protocol is exhibited by its mild conditions, wide substrate scope, and scalable preparation. Mechanistic studies and DFT calculations proved that the coordination of α-trifluoromethylstyrenes to Ni-catalyst prevents the direct reduction of the alkene and, in turn, promotes the activation of alkyl bromide through halogen atom transfer mechanism.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (2021YFA1500100), the National Natural Science Foundation of China (22031008) and the Science Foundation of Wuhan (2020010601012192). The theoretical calculations were performed on the supercomputing system in the Supercomputing Center of Wuhan University.

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Advanced Studies (IAS) and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072, China

    Xingxiu Yan, Shengchun Wang, Zhao Liu, Yujie Luo, Pengjie Wang, Wenyan Shi, Xiaotian Qi, Zhiliang Huang & Aiwen Lei

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  1. Xingxiu Yan
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  2. Shengchun Wang
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  3. Zhao Liu
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  4. Yujie Luo
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  7. Xiaotian Qi
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  8. Zhiliang Huang
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Correspondence to Xiaotian Qi, Zhiliang Huang or Aiwen Lei.

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Supporting information The supporting information is available online at http://chem.scichina.com and http://link.springer.com/journal/11426. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.

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Yan, X., Wang, S., Liu, Z. et al. Precise electro-reduction of alkyl halides for radical defluorinative alkylation. Sci. China Chem. 65, 762–770 (2022). https://doi.org/10.1007/s11426-021-1210-y

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  • DOI: https://doi.org/10.1007/s11426-021-1210-y

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