Hengzhao Li, Kemeng Wang, Wangyu Zhao, Xinxin Li, Yijing Fu, Hainam Do, Jie An, Zhaonong Hu
{"title":"Highly Chemoselective Synthesis of α, α-Dideuterio Amines by the Reductive Deuteration of Thioamides Using Mild SmI2–D2O","authors":"Hengzhao Li, Kemeng Wang, Wangyu Zhao, Xinxin Li, Yijing Fu, Hainam Do, Jie An, Zhaonong Hu","doi":"10.1021/acs.orglett.4c03434","DOIUrl":null,"url":null,"abstract":"An efficient and chemoselective protocol for the single-electron-transfer (SET) reductive deuteration of thioamides using SmI<sub>2</sub> and D<sub>2</sub>O is reported. This method uniquely produces α,α-dideuterio amines via a thio-ketyl radical intermediate without generating alcohol byproducts, distinguishing it from the SET reduction of amides. The inherent high reactivity of thioamides obviates the need for ligands like Et<sub>3</sub>N to improve the reducing power of SmI<sub>2</sub>, thereby enabling milder reaction conditions that are compatible with a broad range of sensitive functional groups. This protocol tolerates both primary and secondary aliphatic and aromatic thioamides, leading to the synthesis of 27 α,α-dideuterio amines and valuable deuterated nitrogen heterocycles with >95% deuterium incorporations.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Letters","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.orglett.4c03434","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
An efficient and chemoselective protocol for the single-electron-transfer (SET) reductive deuteration of thioamides using SmI2 and D2O is reported. This method uniquely produces α,α-dideuterio amines via a thio-ketyl radical intermediate without generating alcohol byproducts, distinguishing it from the SET reduction of amides. The inherent high reactivity of thioamides obviates the need for ligands like Et3N to improve the reducing power of SmI2, thereby enabling milder reaction conditions that are compatible with a broad range of sensitive functional groups. This protocol tolerates both primary and secondary aliphatic and aromatic thioamides, leading to the synthesis of 27 α,α-dideuterio amines and valuable deuterated nitrogen heterocycles with >95% deuterium incorporations.
期刊介绍:
Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.