可见光诱导的1,2,4-三嗪-3,5(2,4)-二酮通过罕见的1,2-氢原子转移进行C-H烷基化反应

Visible-Light-Induced C-H Alkylation of 1,2,4-Triazine-3,5(2,4)-diones via Infrequent 1,2-Hydrogen-Atom Transfer.

作者信息

Wang Mi, Wang Yangyang, Wang Jie, Zhu Yafei, Zhang Penghua, Zhang Cuimei, Chen Jian, Guo Li, Lv Guanghui, Wu Yong

机构信息

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, No. 17 Southern Renmin Road, Chengdu, Sichuan 610041, China.

Department of Pharmacy, Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, China.

出版信息

J Org Chem. 2025 May 30;90(21):7049-7061. doi: 10.1021/acs.joc.5c00635. Epub 2025 May 19.

DOI:10.1021/acs.joc.5c00635

PMID:40388596

Abstract

1,2,4-Triazine-3,5(2,4-diones are widely present in various drug molecules and bioactive molecules. A visible-light-driven C-H alkylation of 1,2,4-triazine-3,5(2,4)-diones via 1,2-hydrogen-atom transfer (1,2-HAT) of amide radicals is first reported, providing an environmentally friendly and sustainable pathway to enrich the structural and functional diversity of 1,2,4-triazine-3,5(2,4)-diones. This novel protocol is characterized by mild and metal-free reaction conditions, an operationally simple method, and good functional group tolerance. To our delight, other heterocycles, such as isoquinoline and coumarin, also undergo alkylation reactions to construct C(sp)-C(sp) bonds via infrequent 1,2-HAT under current conditions.

摘要

1,2,4-三嗪-3,5(2,4)-二酮广泛存在于各种药物分子和生物活性分子中。首次报道了通过酰胺自由基的1,2-氢原子转移（1,2-HAT）实现可见光驱动的1,2,4-三嗪-3,5(2,4)-二酮的C-H烷基化反应，为丰富1,2,4-三嗪-3,5(2,4)-二酮的结构和功能多样性提供了一条环境友好且可持续的途径。这一新颖的方法具有反应条件温和、无金属、操作简便以及官能团耐受性良好的特点。令人高兴的是，在当前条件下，其他杂环化合物，如异喹啉和香豆素，也能通过罕见的1,2-HAT发生烷基化反应以构建C(sp)-C(sp)键。