{"title":"Ni/Cu Dual-Catalyzed Propargylation for the Stereodivergent Synthesis of Methohexital.","authors":"Xihao Chang, Jiayin Zhang, Xiang Cheng, Xianhai Lv, Chang Guo","doi":"10.1002/advs.202406764","DOIUrl":null,"url":null,"abstract":"<p><p>The development of efficient methodologies for the controlled manufacture of specific stereoisomers bearing quaternary stereocenters has prompted advances in a variety of scientific disciplines including pharmaceutical chemistry, materials science, and chemical biology. However, complete control of the absolute and relative stereochemical configurations of alkyne derivatives remains an unmet synthetic challenge. Herein, a Ni/Cu dual-catalyzed asymmetric propargylic substitution reaction is presented to produce propargylated products with all-carbon quaternary stereocenters in high yields with significant diastereo- and enantioselectivities (up to >20:1 dr, >99% ee). The synthesis of all stereochemical variants of methohexital, a widely used sedative-hypnotic drug, exemplifies the efficacy of dual-catalyzed stereodivergent propargylation.</p>","PeriodicalId":117,"journal":{"name":"Advanced Science","volume":null,"pages":null},"PeriodicalIF":14.3000,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advanced Science","FirstCategoryId":"88","ListUrlMain":"https://doi.org/10.1002/advs.202406764","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
The development of efficient methodologies for the controlled manufacture of specific stereoisomers bearing quaternary stereocenters has prompted advances in a variety of scientific disciplines including pharmaceutical chemistry, materials science, and chemical biology. However, complete control of the absolute and relative stereochemical configurations of alkyne derivatives remains an unmet synthetic challenge. Herein, a Ni/Cu dual-catalyzed asymmetric propargylic substitution reaction is presented to produce propargylated products with all-carbon quaternary stereocenters in high yields with significant diastereo- and enantioselectivities (up to >20:1 dr, >99% ee). The synthesis of all stereochemical variants of methohexital, a widely used sedative-hypnotic drug, exemplifies the efficacy of dual-catalyzed stereodivergent propargylation.
期刊介绍:
Advanced Science is a prestigious open access journal that focuses on interdisciplinary research in materials science, physics, chemistry, medical and life sciences, and engineering. The journal aims to promote cutting-edge research by employing a rigorous and impartial review process. It is committed to presenting research articles with the highest quality production standards, ensuring maximum accessibility of top scientific findings. With its vibrant and innovative publication platform, Advanced Science seeks to revolutionize the dissemination and organization of scientific knowledge.