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Alkene 1,1-difunctionalizations via organometallic-radical relay

Nature Catalysis volume 6, pages 1030–1041 (2023)Cite this article

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Abstract

Radical reactions play an important role in modern organic synthetic chemistry. The generation of carbon radicals from the homolytic cleavage of carbon–metal bonds has been widely studied as a fundamental step in organometallic chemistry. However, the implementation of this phenomenon in catalysed cascade reactions, that is, an organometallic-radical relay, is a highly challenging undertaking due to transient radicals generated from these thermodynamically disfavoured endergonic processes. Here we disclose a set of catalytic alkene 1,1-difunctionalization reactions conceptually based on an organometallic-radical relay. This strategy enables a diversity of sp3/sp2 fragments and aryl groups to be simultaneously introduced to the same carbon of both terminal and internal alkenes with outstanding chemo- and regioselectivity. This study provides a concept for the generation of functionalized benzylic radicals, which are difficult to access by classical protocols, from non-radical feedstock alkenes and arylboronic acids.

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Fig. 1: Radical generation and alkene 1,1-bisfunctionalizations.
Fig. 2: Reaction discovery and scope of radical acceptors.
Fig. 3: Scope of alkenes.
Fig. 4: Substrate scope and synthetic applications.
Fig. 5: Mechanistic studies.
Fig. 6: DFT calculations.
Fig. 7: DFT calculations for alkene competition.

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Data availability

All information relating to optimization studies, experimental procedures, mechanistic studies, DFT calculations, NMR spectra and high-resolution mass spectrometry are available in the Supplementary Information. All other data are available from the corresponding authors upon request.

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Acknowledgements

The National Nature Science Foundation of China (22122107), the Fundamental Research Funds for Central Universities (2042022kf0026) and the Shanghai Committee of Science and Technology (grant number 21DZ1100100) are acknowledged for financial support. Y. Tong (Wuhan University) is kindly acknowledged for HRMS analysis. The numerical calculations in this paper were performed on the supercomputing system of the Super-computing Center of Wuhan University.

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Authors and Affiliations

  1. The Institute for Advanced Studies, Wuhan University, Wuhan, Hubei, China

    Dong Wu, Weiyu Kong, Yang Bao, Dengyang Zhao & Guoyin Yin

  2. Shanghai AI Laboratory, Shanghai, China

    Yuqiang Li

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Contributions

G.Y. designed the project and directed the work. D.W., W.K., Y.B. and D.Z. performed all the synthetic experiments. Y.L. performed all the DFT calculations. G.Y. and D.W. wrote the manuscript.

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Correspondence to Yuqiang Li or Guoyin Yin.

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Nature Catalysis thanks Mingbin Yuan and the other, anonymous, reviewers for their contribution to the peer review of this work.

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DFT coordinates for optimized structures.

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Wu, D., Kong, W., Bao, Y. et al. Alkene 1,1-difunctionalizations via organometallic-radical relay. Nat Catal 6, 1030–1041 (2023). https://doi.org/10.1038/s41929-023-01032-0

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