Faxiang Bu, Yuqi Deng, Jie Xu, Dali Yang, Yan Li, Wu Li, Aiwen Lei
{"title":"炔和杂环烯的电催化还原脱氘反应","authors":"Faxiang Bu, Yuqi Deng, Jie Xu, Dali Yang, Yan Li, Wu Li, Aiwen Lei","doi":"10.1038/s41586-024-07989-7","DOIUrl":null,"url":null,"abstract":"<p>The incorporation of deuterium to organic molecules has widespread applications in medicinal chemistry and material science<sup>1,2</sup>. For example, deuterated drugs e.g. Austedo<sup>3</sup>, Donafenib<sup>4</sup> and Sotyktu<sup>5</sup> were recently approved. There are various methods for the synthesis of deuterated compounds with high deuterium incorporation<sup>6</sup>. 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<sub>2</sub>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<sub>2</sub>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.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":null,"pages":null},"PeriodicalIF":50.5000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Electrocatalytic reductive deuteration of arenes and heteroarenes\",\"authors\":\"Faxiang Bu, Yuqi Deng, Jie Xu, Dali Yang, Yan Li, Wu Li, Aiwen Lei\",\"doi\":\"10.1038/s41586-024-07989-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The incorporation of deuterium to organic molecules has widespread applications in medicinal chemistry and material science<sup>1,2</sup>. For example, deuterated drugs e.g. Austedo<sup>3</sup>, Donafenib<sup>4</sup> and Sotyktu<sup>5</sup> were recently approved. There are various methods for the synthesis of deuterated compounds with high deuterium incorporation<sup>6</sup>. 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<sub>2</sub>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<sub>2</sub>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.</p>\",\"PeriodicalId\":18787,\"journal\":{\"name\":\"Nature\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":50.5000,\"publicationDate\":\"2024-08-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41586-024-07989-7\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41586-024-07989-7","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
Electrocatalytic reductive deuteration of arenes and heteroarenes
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.
期刊介绍:
Nature is a prestigious international journal that publishes peer-reviewed research in various scientific and technological fields. The selection of articles is based on criteria such as originality, importance, interdisciplinary relevance, timeliness, accessibility, elegance, and surprising conclusions. In addition to showcasing significant scientific advances, Nature delivers rapid, authoritative, insightful news, and interpretation of current and upcoming trends impacting science, scientists, and the broader public. The journal serves a dual purpose: firstly, to promptly share noteworthy scientific advances and foster discussions among scientists, and secondly, to ensure the swift dissemination of scientific results globally, emphasizing their significance for knowledge, culture, and daily life.