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Electrochemical oxidative C(sp3)–H cross-coupling with hydrogen evolution

Nature Synthesis volume 2, pages 217–230 (2023)Cite this article

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Abstract

Oxidative C(sp3)–H bond functionalization is a powerful tool in organic synthesis, but the stoichiometric oxidants required for bond formation raise environmental concerns. Electrochemical synthesis is typically carried out under environmentally benign conditions and hence is increasingly used in organic reactions. Recent advances revealed that electrochemical oxidative cross-coupling reactions employing either free radicals or carbocations can be conducted in the absence of external oxidants. In this Review, we outline the electrochemical oxidative C(sp3)–H cross-coupling to C(sp3)–C(X) (X = N, O, S, P, F, I and Br) bonds with hydrogen evolution under external oxidant-free conditions. Two commonly used electrochemical methods, namely direct and indirect oxidation electrolysis, are discussed for C(sp3)–H activation. The outline of electrochemical oxidative C(sp3)–H cross-coupling is organized based on the reactive intermediates (C(sp3)–M, a C(sp3) radical or a C(sp3) cation). Electrochemical asymmetric C(sp3)–H cross-coupling and late-stage functionalization of C(sp3)–H bonds in complex molecules are included to demonstrate the utility. Future perspectives for the development of electrochemical C(sp3)–H bond functionalization are proposed.

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Fig. 1: Oxidative C(sp3)–H cross-coupling.
Fig. 2: Pathway for activated C(sp3)–H bonds and unactivated C(sp3)–H bonds in electrochemical oxidative C(sp3)–H cross-couplings.
Fig. 3: ET to afford a C(sp3) radical through SET.
Fig. 4: HAT process in electrocatalytic C(sp3)–H cross-coupling.
Fig. 5: C(sp3)–H functionalization involving C(sp3) carbocation.
Fig. 6: Electrochemical palladium-catalysed oxidative C(sp3)–H functionalization.
Fig. 7: Electrochemical asymmetric functionalization of C(sp3)–H.
Fig. 8: LSF of C C(sp3)–H bonds by electrocatalysis.

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Acknowledgements

This work was supported by the National Key R&D Program of China (no. 2022YFA1505100 and 2021YFA1500100), National Natural Science Foundation of China (22031008) and Science Foundation of Wuhan (2020010601012192). This research work was funded by the Institution Fund Projects under grant IFPRP 263-135-1442. Also, we gratefully acknowledge technical and financial support from the Ministry of Education and Deanship of Scientific Research (DSR), King Abdulaziz University, Jeddah, Saudi Arabia

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

    Zhaoliang Yang, Wenyan Shi, Hong Yi & Aiwen Lei

  2. Department of Chemical and Materials Engineering, Center of Research Excellence in Renewable Energy and Power Systems, King Abdulaziz University, Jeddah, Saudi Arabia

    Hesham Alhumade

Authors
  1. Zhaoliang Yang
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  2. Wenyan Shi
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  3. Hesham Alhumade
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  4. Hong Yi
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  5. Aiwen Lei
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Contributions

A.L. and H.Y. designed and directed the investigations and composed the manuscript with revisions provided by the other authors.. Z.Y., H.A. and W.S. completed the full text of the writing.

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Correspondence to Hong Yi or Aiwen Lei.

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Nature Synthesis thanks the anonymous reviewers for their contribution to the peer review of this work. Primary Handling Editor: Alison Stoddart, in collaboration with the Nature Synthesis team.

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Yang, Z., Shi, W., Alhumade, H. et al. Electrochemical oxidative C(sp3)–H cross-coupling with hydrogen evolution. Nat. Synth 2, 217–230 (2023). https://doi.org/10.1038/s44160-022-00221-2

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