深圳理工大学殷勤团队基于动态动力学拆分的外消旋2-取代喹啉不对称转移加氢反应。相关研究成果发表在2025年1月22日出版的《美国化学会杂志》。

手性四氢喹啉（THQs）的合成引起了药物化学家的极大兴趣，因为它们经常作为生物活性化合物中的药效团存在。虽然现有的合成方法主要集中在具有单个或多个内环手性中心的THQs上，但选择性构建具有内环和外环手性中心的THR仍然是一个需要进一步发展的重大挑战。

该研究介绍了一种基于动态动力学拆分（DKR）的外消旋2-取代喹啉转移氢化方法，该方法以优异的产率和立体选择性制备结构新颖的手性THQs，具有连续的内环和外环手性中心（59个例子，通常>20:1 dr和>90%ee，最多三个连续的立体中心）。

该方法为缺电子芳香族N-杂环的不对称转化提供了一种机械上新颖的方法，并为拓展药物化学的手性N-杂环化学空间提供了一条创新途径。

附：英文原文

Title: Dynamic Kinetic Resolution-Based Asymmetric Transfer Hydrogenation of Racemic 2-Substituted Quinolines

Author: Ming-Rong Liang, Xian Du, Jian Lin, Nianxin Rong, Xiaohang Zhan, Xinyue Mao, Haokun Zhuang, Tianyu Niu, Qin Yin

Issue&Volume: January 22, 2025

Abstract: The synthesis of chiral tetrahydroquinolines (THQs) has garnered significant interest from medicinal chemists due to their frequent presence as pharmacophores in bioactive compounds. While existing synthetic methods have primarily focused on THQs with single or multiple endocyclic chiral centers, the selective construction of THQs with both endo- and exo-cyclic chiral centers remains a significant challenge that requires further development. This study introduces a dynamic kinetic resolution (DKR)-based transfer hydrogenation of racemic 2-substituted quinolines, which yields structurally novel chiral THQs with consecutive endo- and exo-cyclic chiral centers in excellent yields and stereoselectivities (59 examples, with generally >20:1 dr and >90% ee, up to three consecutive stereocenters). Our approach offers a mechanistically novel method for the asymmetric transformation of electron-deficient aromatic N-heterocycles and presents an innovative way to expand the chiral N-heterocycle chemical space for medicinal chemistry.

DOI: 10.1021/jacs.4c14200

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c14200