Zhang Yun, Zhang Zheng-Qian, Du Yao, Nie Jia-Huan, Wang Yan, Cui Bao-Dong, Mou Xue-Qing, Zhou Ming-Qiang, Chen Yong-Zheng
Key Laboratory of Biocatalysis & Chiral Drug Synthesis of Guizhou Province, Generic Drug Research Center of Guizhou Province, Green Pharmaceuticals Engineering Research Center of Guizhou Province, School of Pharmacy, Zunyi Medical University, Zunyi 563006, P. R. China.
Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563006, P. R. China.
J Org Chem. 2024 Aug 16;89(16):11513-11524. doi: 10.1021/acs.joc.4c01229. Epub 2024 Jul 25.
-Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access -acyl/sulfonyl-α-functionalized THIQs. This method features the use of oxygen (from air) as the green oxidant, high atom and step economy, and decent structural diversity. The synthetic applicability of the method was further demonstrated via the facile construction of valuable bioactive molecules. Mechanistic studies indicated that oxidation with singlet oxygen and the acceptor-less dehydrogenation were involved in the photoredox process.
酰基/磺酰基-α-官能化的1,2,3,4-四氢异喹啉（THIQs）是有机合成和药物发现中重要的结构基序。然而，实现THIQs直接双官能化的一锅法仍然具有挑战性。在此，我们报道了一种光介导的一锅三组分策略来合成酰基/磺酰基-α-官能化的THIQs。该方法的特点是使用氧气（来自空气）作为绿色氧化剂，具有高原子经济性和步骤经济性，以及良好的结构多样性。通过简便构建有价值的生物活性分子，进一步证明了该方法的合成适用性。机理研究表明，单线态氧氧化和无受体脱氢参与了光氧化还原过程。
