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Hypervalent iodine-mediated gem-difluorination of vinyl halides enabled by exclusive 1,2-halo migration

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Abstract

β-Difluorinated alkyl halides are of significant value in the modular synthesis of gem-difluorinated molecules. An exclusive 1,2-halo migratory gem-difluorination of vinyl halides with in situ-generated PhIF2·HF is described. This protocol provides a general and practical approach towards a wide variety of β-difluorinated alkyl bromides. Both α- and β-bromoalkyl alkenes are suitable substrates, leading to two distinct types of products. The extension of this protocol to vinyl chloride and iodide are also feasible. The synthetic versatility of this method has been highlighted by the late-stage modification of complex small molecules and further transformations of the β-difluorinated alkyl halides to valuable CF2-containing compounds.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21961047, 21901266, 21971261, 22022114).

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Authors and Affiliations

  1. Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi, 563000, China

    Chenglong Li, Yangzhen Liao, Xuemei Tan, Xiaozu Liu & Peijun Liu

  2. Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China

    Xiaozu Liu & Peijun Liu

  3. Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, China

    Wen-Xin Lv & Honggen Wang

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  1. Chenglong Li
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  2. Yangzhen Liao
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  4. Xiaozu Liu
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  5. Peijun Liu
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  7. Honggen Wang
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Correspondence to Peijun Liu or Honggen Wang.

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Li, C., Liao, Y., Tan, X. et al. Hypervalent iodine-mediated gem-difluorination of vinyl halides enabled by exclusive 1,2-halo migration. Sci. China Chem. 64, 999–1003 (2021). https://doi.org/10.1007/s11426-021-9965-9

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  • DOI: https://doi.org/10.1007/s11426-021-9965-9

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