Du Hai-Wu, Jia Jun-Song, Chen Xiao-Yi, Yuan Zhang-Yin, Lin Jia-Ni, Li Yu-Long, Yu Qiong, Shu Wei
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Shenzhen Grubbs Institute, Guangming Advanced Research Institute, Department of Chemistry, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology Shenzhen 518055 Guangdong P. R. China
College of Chemistry and Environmental Engineering, Innovation Center for Chenguang High Performance Fluorine Material, Key Laboratory of Green Catalysis of Higher Education Institutes of Sichuan, Sichuan University of Science and Engineering Zigong 643000 P. R. China
Chem Sci. 2025 May 22. doi: 10.1039/d5sc00665a.
Dihydroisoquinolinediones are ubiquitous nitrogen-containing fused heterocyclic units in natural products, drug molecules, and functional materials. However, straightforward synthesis of dihydroisoquinolinediones from simple and readily available precursors remains challenging and underdeveloped. Herein, we developed an unprecedented photocatalytic [4 + 2] skeleton-editing strategy enabled direct synthesis of dihydroisoquinoline-1,4-diones from vinyl azides and carboxylic NHPI esters. The key to success is the use of NHPIs as bifunctional reagents and in the skeleton-edit enabled [4 + 2] cyclization cascade. Notably, vinyl azides serve as α-primary amino alkyl radicals followed by a radical initiated ring-enlargement event. Impressively, the reaction provides convergent access to identical dihydroisoquinolinedione from different NHPIs and divergent access to different dihydroisoquinolinediones from identical NHPI. The reaction cleaves two C-N bonds and forges one C-N bond, two C-C bonds and a ring.
二氢异喹啉二酮是天然产物、药物分子和功能材料中普遍存在的含氮稠合杂环单元。然而，从简单易得的前体直接合成二氢异喹啉二酮仍然具有挑战性且发展不足。在此，我们开发了一种前所未有的光催化[4 + 2]骨架编辑策略，能够从乙烯基叠氮化物和羧酸NHPI酯直接合成二氢异喹啉-1,4-二酮。成功的关键是使用NHPI作为双功能试剂，并参与骨架编辑的[4 + 2]环化级联反应。值得注意的是，乙烯基叠氮化物作为α-伯氨基烷基自由基，随后发生自由基引发的扩环反应。令人印象深刻的是，该反应能从不同的NHPI收敛合成相同的二氢异喹啉二酮，也能从相同的NHPI发散合成不同的二氢异喹啉二酮。该反应断裂两个C-N键，形成一个C-N键、两个C-C键和一个环。
