{"title":"铜催化的不对称环化亚胺化:锻造吲哚基立体硫(IV)中心和atrosomomer手性","authors":"Xiaowu Fang, , , Fengrui Xiang, , , Yue Zhao, , and , Zhuangzhi Shi*, ","doi":"10.1021/acscentsci.5c00909","DOIUrl":null,"url":null,"abstract":"<p >The structural prominence of indole-based sulfur-containing compounds in pharmacologically relevant substances stems from their versatile biofunctional capabilities. Despite their significance, the stereogenic elements embedded in these structures have frequently been overlooked in drug discovery endeavors primarily due to the absence of efficient synthetic methodologies. Here, we introduce a groundbreaking strategy for the enantioselective synthesis of indole-based sulfinamides via a copper-catalyzed asymmetric nucleophilic cyclization and sulfinamidation reaction. Utilizing <i>ortho</i>-alkynylanilines and sulfinylamines, this method achieves a broad spectrum of sulfinamides with complete atom economy, establishing a new paradigm in synthetic efficiency. Our approach not only facilitates the formation of S-chirogenic sulfinamides but also concurrently constructs products featuring both stereogenic sulfur and atropisomeric chirality. Comprehensive mechanistic investigations, complemented by density functional theory (DFT) calculations, provide deep insights into the reaction mechanism, particularly in elucidating the S-stereogenic and atropisomeric control during the cyclization and sulfinamidation processes.</p><p >A copper-catalyzed cyclizative sulfinamidation strategy enables facile synthesis of indole-based sulfinamides with simultaneous control of stereogenic sulfur and atropisomeric chirality.</p>","PeriodicalId":10,"journal":{"name":"ACS Central Science","volume":"11 9","pages":"1762–1772"},"PeriodicalIF":10.4000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00909","citationCount":"0","resultStr":"{\"title\":\"Copper-Catalyzed Asymmetric Cyclizative Sulfinamidation: Forging Indole-Based Stereogenic Sulfur(IV) Centers and Atropisomeric Chirality\",\"authors\":\"Xiaowu Fang, , , Fengrui Xiang, , , Yue Zhao, , and , Zhuangzhi Shi*, \",\"doi\":\"10.1021/acscentsci.5c00909\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >The structural prominence of indole-based sulfur-containing compounds in pharmacologically relevant substances stems from their versatile biofunctional capabilities. Despite their significance, the stereogenic elements embedded in these structures have frequently been overlooked in drug discovery endeavors primarily due to the absence of efficient synthetic methodologies. Here, we introduce a groundbreaking strategy for the enantioselective synthesis of indole-based sulfinamides via a copper-catalyzed asymmetric nucleophilic cyclization and sulfinamidation reaction. Utilizing <i>ortho</i>-alkynylanilines and sulfinylamines, this method achieves a broad spectrum of sulfinamides with complete atom economy, establishing a new paradigm in synthetic efficiency. Our approach not only facilitates the formation of S-chirogenic sulfinamides but also concurrently constructs products featuring both stereogenic sulfur and atropisomeric chirality. Comprehensive mechanistic investigations, complemented by density functional theory (DFT) calculations, provide deep insights into the reaction mechanism, particularly in elucidating the S-stereogenic and atropisomeric control during the cyclization and sulfinamidation processes.</p><p >A copper-catalyzed cyclizative sulfinamidation strategy enables facile synthesis of indole-based sulfinamides with simultaneous control of stereogenic sulfur and atropisomeric chirality.</p>\",\"PeriodicalId\":10,\"journal\":{\"name\":\"ACS Central Science\",\"volume\":\"11 9\",\"pages\":\"1762–1772\"},\"PeriodicalIF\":10.4000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://pubs.acs.org/doi/pdf/10.1021/acscentsci.5c00909\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Central Science\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acscentsci.5c00909\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Central Science","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acscentsci.5c00909","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
The structural prominence of indole-based sulfur-containing compounds in pharmacologically relevant substances stems from their versatile biofunctional capabilities. Despite their significance, the stereogenic elements embedded in these structures have frequently been overlooked in drug discovery endeavors primarily due to the absence of efficient synthetic methodologies. Here, we introduce a groundbreaking strategy for the enantioselective synthesis of indole-based sulfinamides via a copper-catalyzed asymmetric nucleophilic cyclization and sulfinamidation reaction. Utilizing ortho-alkynylanilines and sulfinylamines, this method achieves a broad spectrum of sulfinamides with complete atom economy, establishing a new paradigm in synthetic efficiency. Our approach not only facilitates the formation of S-chirogenic sulfinamides but also concurrently constructs products featuring both stereogenic sulfur and atropisomeric chirality. Comprehensive mechanistic investigations, complemented by density functional theory (DFT) calculations, provide deep insights into the reaction mechanism, particularly in elucidating the S-stereogenic and atropisomeric control during the cyclization and sulfinamidation processes.
A copper-catalyzed cyclizative sulfinamidation strategy enables facile synthesis of indole-based sulfinamides with simultaneous control of stereogenic sulfur and atropisomeric chirality.
期刊介绍:
ACS Central Science publishes significant primary reports on research in chemistry and allied fields where chemical approaches are pivotal. As the first fully open-access journal by the American Chemical Society, it covers compelling and important contributions to the broad chemistry and scientific community. "Central science," a term popularized nearly 40 years ago, emphasizes chemistry's central role in connecting physical and life sciences, and fundamental sciences with applied disciplines like medicine and engineering. The journal focuses on exceptional quality articles, addressing advances in fundamental chemistry and interdisciplinary research.