武汉大学雷爱文团队报道了芳烃和杂芳烃的电催化还原氘化反应。相关研究成果发表在2024年8月29日出版的《自然》。

氘与有机分子的结合在药物化学和材料科学中具有广泛的应用。例如，氘代药物，如最近获得批准的Austedo、Donafenib和Sotyktu。有多种方法可以合成氘含量高的氘化化合物。然而，芳香烃（普遍存在的化学原料）还原氘化为饱和环状化合物的方法很少实现。

该文中，研究人员描述了一种可扩展的通用电催化方法，使用制备的氮掺杂电极和D₂O对（杂）芳烃进行还原氘化和氘化脱氟，得到全氘化和饱和氘化产物。该方案已成功应用于13种高度氘化药物分子的合成。机理研究表明，在氮掺杂Ru电极存在下，D₂O电解产生的Ru-D物种是直接还原芳香族化合物的关键中间体。

这种快速且经济高效的方法用于制备高度D-标记的饱和（杂环）化合物，可应用于药物开发和代谢研究。

附：英文原文

Title: Electrocatalytic reductive deuteration of arenes and heteroarenes

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

Issue&Volume: 2024-08-29

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.

DOI: 10.1038/s41586-024-07989-7

Source: https://www.nature.com/articles/s41586-024-07989-7