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Electrocatalytic reductive deuteration of arenes and heteroarenes.

Faxiang BuYuqi DengJie XuDali YangYan LiWu LiAiwen Lei
Published in: Nature (2024)
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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