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Radical-triggered translocation of C–C double bond and functional group

Nature Chemistry volume 16, pages 1621–1629 (2024)Cite this article

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Abstract

Multi-site functionalization of molecules provides a potent approach to accessing intricate compounds. However, simultaneous functionalization of the reactive site and the inert remote C(sp3)–H poses a formidable challenge, as chemical reactions conventionally occur at the most active site. In addition, achieving precise control over site selectivity for remote C(sp3)–H activation presents an additional hurdle. Here we report an alternative modular method for alkene difunctionalization, encompassing radical-triggered translocation of functional groups and remote C(sp3)–H desaturation via photo/cobalt dual catalysis. By systematically combining radical addition, functional group migration and cobalt-promoted hydrogen atom transfer, we successfully effectuate the translocation of the carbon–carbon double bond and another functional group with precise site selectivity and remarkable E/Z selectivity. This redox-neutral approach shows good compatibility with diverse fluoroalkyl and sulfonyl radical precursors, enabling the migration of benzoyloxy, acetoxy, formyl, cyano and heteroaryl groups. This protocol offers a resolution for the simultaneous transformation of manifold sites.

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Fig. 1: Strategies for FG translocation.
Fig. 2: Mechanistic studies.
Fig. 3: DFT calculation and plausible mechanism.

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Data availability

Details about the materials and methods, experimental procedures, mechanistic studies, characterization data and NMR spectra are available in Supplementary Information. The authors declare that all the data supporting the findings of this study are available within the article and its Supplementary Information.

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Acknowledgements

This work was supported by the National Key R&D Program of China no. 2022YFA1505100 (H.Y.), no. 2023YFA1508600 (X.Q.) and no. 2021YFA1500104 (A.L.), National Natural Science Foundation of China no. 22031008 (A.L.) and no. 22201222 (X.Q.), Science Foundation of Wuhan no. 2020010601012192 (A.L.), and China Postdoctoral Science Foundation no. 2022M722455 (S.W.) and the supercomputing system in the Supercomputing Center of Wuhan University (X.Q.). We thank the Core Facility of Wuhan University for the measurement of TAS.

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Author notes

  1. These authors contributed equally: Shengchun Wang, Xu Luo, Yuan Wang.

Authors and Affiliations

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

    Shengchun Wang, Xu Luo, Yuan Wang, Zhao Liu, Yi Yu, Xuejie Wang, Demin Ren, Pengjie Wang, Yi-Hung Chen, Xiaotian Qi, Hong Yi & Aiwen Lei

  2. State Key Laboratory of Power Grid Environmental Protection, School of Electrical Engineering and Automation, Wuhan University, Wuhan, P. R. China

    Xiaotian Qi & Aiwen Lei

  3. National Engineering Research Center for Carbohydrate Synthesis, Jiangxi Normal University, Nanchang, P. R. China

    Aiwen Lei

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Contributions

A.L. and S.W. conceived the work. S.W., H.Y., X.L., Y.-H.C. and A.L. designed the experiments and analysed the data. X.L., Y.W., S.W., X.W. and D.R. performed the synthetic experiments. S.W. and P.W. contributed to EPR data. Z.L., Y.Y. and X.Q. contributed to the DFT calculation. S.W. wrote the original paper, which was revised by all authors.

Corresponding authors

Correspondence to Xiaotian Qi, Hong Yi or Aiwen Lei.

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Nature Chemistry thanks Chen Zhu and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Supplementary Information

Supplementary Figs. 1–23, Tables 1–6, Discussion for scope limitations and Product derivatization.

Supplementary Data 1

The computational structures used in this study.

Supplementary Data 2

NMR spectra of starting materials.

Supplementary Data 3

NMR spectra of products.

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Wang, S., Luo, X., Wang, Y. et al. Radical-triggered translocation of C–C double bond and functional group. Nat. Chem. 16, 1621–1629 (2024). https://doi.org/10.1038/s41557-024-01633-7

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