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Boron clusters as efficient shuttles for electrocatalytic deuterium labelling via radical H/D exchange

Nature Catalysis volume 8, pages 784–793 (2025)Cite this article

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Abstract

Deuterium labelling has widespread applications in medicinal chemistry, chemical science and materials science. Hydrogen isotope exchange for deuterium labelling of C(sp3)–H bonds under mild conditions remains a key challenge in labelling reactions. Here we show an electrocatalytic strategy enabling rapid (<10 min) deuteration of natural products and pharmaceuticals. Using clusters containing boron, (TBA)2B10H10, as the electrocatalyst, anodically generated [B10H10]•− intermediates undergo hydrogen-atom transfer with C(sp3)–H/D bonds, forming stabilized [B10H10H/D]− species. Cathodic reduction then triggers selective H/D exchange with carbon radicals, regenerating the catalyst. The boron cluster modulates reactive H/D radicals via reversible electron transfer, balancing radical activity and stability to enable efficient labelling without harsh reagents. This method achieves broad substrate compatibility and high deuterium incorporation and is demonstrated using complex drug molecules. By integrating electrocatalysis with boron cluster-mediated hydrogen-atom transfer, we provide a general platform for C(sp3)–H deuteration, advancing isotope-labelling applications in synthetic and medicinal chemistry.

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Fig. 1: Deuteration of C(sp3)–H bonds via radical coupling.
Fig. 2: Mechanistic investigations.
Fig. 3: Control experiments and substrate scope.
Fig. 4: Substrate scope.

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All relevant data are included in the Article and its Supplementary Information or are available from the corresponding authors upon reasonable request.

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Acknowledgements

This work was supported by the National Key R&D Program of China (grant no. 2021YFA1500104, A.L.), the National Natural Science Foundation of China (grant no. 22031008, A.L.; 212200007, W.L.; 22371214, 22179100, H.Z.). The numerical calculations in this paper were done on the supercomputing system in the Supercomputing Center of Wuhan University. We thank Q. Lu, W. Liu, X. Dong, H. Wang, Y. Liu and L. Zeng for their help with this work.

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  1. These authors contributed equally: Meng He, Xuefan Deng, Fengze Yao.

Authors and Affiliations

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

    Meng He, Xuefan Deng, Fengze Yao, Yachun Wang, Yuan Gao, Pengjie Wang, Qiongqiong Wan, Kaixiang Chen, Liwei Wang, Hong Yi, Haibo Zhang, Wu Li & Aiwen Lei

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Contributions

M.H., X.D. and F.Y. contributed equally to this work. A.L. and W.L. supervised the project and provided guidance on the project. A.L., W.L. and M.H. conceived and designed the study. M.H., X.D., F.Y., Y.W. and Y.G. performed the experiments. P.W. performed the EPR studies. Q.W. and K.C. performed the in situ mass spectrometry studies. M.H., X.D., H.Y., H.Z., W.L. and A.L. wrote and revised the paper. All authors contributed to the analysis.

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Correspondence to Haibo Zhang, Wu Li or Aiwen Lei.

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Nature Catalysis thanks Gunnar Jeschke and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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He, M., Deng, X., Yao, F. et al. Boron clusters as efficient shuttles for electrocatalytic deuterium labelling via radical H/D exchange. Nat Catal 8, 784–793 (2025). https://doi.org/10.1038/s41929-025-01379-6

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