Abstract
The incorporation of deuterium to organic molecules has widespread applications in medicinal chemistry and material science1,2. For example, deuterated drugs e.g. Austedo3, Donafenib4 and Sotyktu5 were recently approved. There are various methods for the synthesis of deuterated compounds with high deuterium incorporation6. 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 D2O, 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 D2O 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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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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