新加坡国立大学赵宇团队报道了铱催化外消旋1,5-二醇合成哌啶和四氢异喹啉的对映收敛结构。相关研究成果于2024年12月17日发表于国际一流学术期刊《美国化学会杂志》。

该文中，研究人员报道了一种从现成的外消旋1,5-二醇，一步法合成有价值的富对映体哌啶和四氢异喹啉的方法。成功的关键是开发了新的环烯醚催化剂，该催化剂能够以对映体的方式在二醇和胺之间，高效地构建两个C-N键的氧化还原中性结构。

机理研究发现，铱环催化剂在二醇底物中对仲醇和伯醇进行了有趣的优先氧化，这使得芳基-烷基取代醇的分子间胺化，成为这种催化N-杂环合成的对映异构步骤。研究证明了这种催化方法，在制备重要药物和生物活性化合物中的应用。

附：英文原文

Title: Iridium-Catalyzed Enantioconvergent Construction of Piperidines and Tetrahydroisoquinolines from Racemic 1,5-Diols

Author: Huanlin Diao, Kexin Liu, Rong Yu, Jilin Chen, Yongbing Liu, Bin-Miao Yang, Yu Zhao

Issue&Volume: December 17, 2024

Abstract: We report herein a one-step synthesis of valuable enantioenriched piperidines and tetrahydroisoquinolines from readily available racemic 1,5-diols. Key to the success is the development of new iridacycle catalysts that enable  efficient redox-neutral construction of two C–N bonds between diols and amines in an enantioconvergent fashion. Mechanistic studies identified an intriguing preferential oxidation of secondary versus primary alcohol in the diol substrate by the iridacycle catalyst, which set a challenging intermolecular amination of aryl–alkyl-substituted alcohol as the enantiodetermining step for this catalytic N-heterocycle synthesis. Application of this catalytic method to the preparation of important drugs and bioactive compounds is also demonstrated.

DOI: 10.1021/jacs.4c12466

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c12466