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Electrocatalytic reductive deuteration of arenes and heteroarenes

Lei, Aiwen
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Nature ( 2024 ) Cite this article

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Abstract

The incorporation of deuterium to organic molecules has widespread applications in medicinal chemistry and material science 1,2 . For example, deuterated drugs e.g. Austedo 3 , Donafenib 4 and Sotyktu 5 were recently approved. There are various methods for the synthesis of deuterated compounds with high deuterium incorporation 6 . However, the reductive deuteration of aromatic hydrocarbons, ubiquitous chemical feedstocks, to saturated cyclic compounds has rarely been achieved. Here, we describe a scalable and general electrocatalytic method for the reductive deuteration and deuterodefluorination of (hetero)arenes using a prepared nitrogen doped electrode and D 2 O, giving perdeuterated and saturated deuterocarbon products. This protocol has been successfully applied to the synthesis of 13 highly deuterated drug molecules. Mechanistic investigations suggest that the Ru-D species, generated by electrolysis of D 2 O in the presence of nitrogen-doped Ru electrode, are key intermediates that directly reduce aromatic compounds. This quick and cost-effective methodology for the preparation of highly D-labeled saturated (hetero)cycles compounds could be applied in the drug development and metabolism studies.

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Author information

Author notes

  1. These authors contributed equally: Faxiang Bu, Yuqi Deng

Authors and Affiliations

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

    Faxiang Bu, Yuqi Deng, Jie Xu, Dali Yang, Yan Li, Wu Li & Aiwen Lei

Authors

  1. Faxiang Bu

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  2. Yuqi Deng

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  3. Jie Xu

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  4. Dali Yang

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  5. Yan Li

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  6. Wu Li

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  7. Aiwen Lei

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Corresponding authors

Correspondence to Wu Li or Aiwen Lei .

Supplementary information

Supplementary Information

This file contains Supplementary Sections 1–16 including Supplementary Figs. 1–28, Supplementary Data and Supplementary References – see Contents for details.

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Bu, F., Deng, Y., Xu, J. et al. Electrocatalytic reductive deuteration of arenes and heteroarenes. Nature (2024). https://doi.org/10.1038/s41586-024-07989-7

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  • DOI : https://doi.org/10.1038/s41586-024-07989-7

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