自由基介导的官能团迁移-环化构建含氮稠杂芳烃

doi:10.6023/cjoc202512005

摘要/Abstract

含氮杂环是药物及许多功能分子的核心骨架, 其高效合成始终是有机化学的关键问题. 自由基介导的官能团迁移(FGM)策略为烯烃的双官能团化提供了强大工具. 此文利用官能团迁移-环化串联策略, 发展一种步骤经济且条件温和的含氮稠杂环合成新方法. 基于我们前期对对接-迁移反应研究的积累, 通过对关键连接单元的理性设计, 成功开发了一类新型的基于亚砜的杂环化试剂. 在温和的可见光照射条件下, 该试剂能与多种烯烃发生高效的自由基对接-迁移反应, 并引发分子内的串联环化过程, 一步实现多种含氮稠杂芳烃的模块化构建. 反应可在温和的条件下进行, 底物普适性广、官能团兼容性优异, 为复杂药物活性分子的后期修饰提供了绿色、高效的合成工具.

关键词: 自由基反应, 含氮稠杂芳烃, 官能团迁移, 光催化, 环化反应

Nitrogen-containing heteroarenes constitute privileged scaffolds in pharmaceuticals and functional molecules, and their efficient synthesis remains a longstanding objective in organic chemistry. Over the past decade, radical-mediated functional group migration (FGM) has emerged as a powerful strategy for alkene functionalization. Herein, a step-economical and practical method for synthesizing N-heteroarenes directly from alkenes through a functional group migration-cyclization cascade is reported. A new class of heterocyclizing agents featuring a sulfoxide linkage has been designed for this transformation. Under visible-light irradiation, these reagents engage with various alkenes in a radical “dock-migration” process, followed by intramolecular cyclization, enabling the modular construction of diverse N-fused heteroarenes in a single operation. The reaction proceeds under mild conditions, exhibits broad substrate scope and excellent functional group tolerance, and offers a green, efficient synthetic tool for the late-stage modification of complex bioactive molecules.

Key words: radical reactions, N-fused heteroarenes, functional group migration, photocatalysis, cyclization reactions

引用此文

杨珊, 陈亚苏, 朱晨. 自由基介导的官能团迁移-环化构建含氮稠杂芳烃[J]. 有机化学, 2026, 46(4): 1739-1749.

Shan Yang, Yasu Chen, Chen Zhu. Construction of N-Fused Heteroarenes via Radical-Mediated Functional Group Migration-Cyclization[J]. Chinese Journal of Organic Chemistry, 2026, 46(4): 1739-1749.

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Entry	Photocatalyst	Base	Solvent	Yield^b/%
1	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	DMF	47
2	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	CH₃COCH₃	36
3	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	CH₃CN	20
4	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	DCM	45
5	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	EtOAc	49
6	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	THF	52
7	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	DMAc	56
8	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	1,4-Dioxane	0
9	Eosin Y	K₂HPO₄	DMAc	0
10	fac-Ir(ppy)₃	K₂HPO₄	DMAc	47
11	Ru(bpy)₃Cl₂•6H₂O	K₂HPO₄	DMAc	64
12	Ru(bpy)₃Cl₂•6H₂O	K₃PO₄	DMAc	30
13	Ru(bpy)₃Cl₂•6H₂O	Na₂HPO₄	DMAc	52
14^c	Ru(bpy)₃Cl₂•6H₂O	K₂HPO₄	DMAc	73
15^c	None	K₂HPO₄	DMAc	0
16^d	Ru(bpy)₃Cl₂•6H₂O	K₂HPO₄	DMAc	0

Entry	Photocatalyst	Base	Solvent	Yield^b/%
1	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	DMF	47
2	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	CH₃COCH₃	36
3	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	CH₃CN	20
4	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	DCM	45
5	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	EtOAc	49
6	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	THF	52
7	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	DMAc	56
8	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆	K₂HPO₄	1,4-Dioxane	0
9	Eosin Y	K₂HPO₄	DMAc	0
10	fac-Ir(ppy)₃	K₂HPO₄	DMAc	47
11	Ru(bpy)₃Cl₂•6H₂O	K₂HPO₄	DMAc	64
12	Ru(bpy)₃Cl₂•6H₂O	K₃PO₄	DMAc	30
13	Ru(bpy)₃Cl₂•6H₂O	Na₂HPO₄	DMAc	52
14^c	Ru(bpy)₃Cl₂•6H₂O	K₂HPO₄	DMAc	73
15^c	None	K₂HPO₄	DMAc	0
16^d	Ru(bpy)₃Cl₂•6H₂O	K₂HPO₄	DMAc	0

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