Ma Yangyang, Zhang Hua, Zhou Zhonghao, Yang Chenyang, Chang Wenxiao, Li Mohan, Zheng Yapei, Zhang Weizhuang, Yue Huan, Chen Changdong, La Ming, Han Yongjun
School of Chemical & Environmental Engineering, Pingdingshan University, Pingdingshan 467000, China.
College of Medicine, Pingdingshan University, Pingdingshan 467000, China.
Int J Mol Sci. 2025 Jul 23;26(15):7105. doi: 10.3390/ijms26157105.
Our work introduces a facile and efficient metal-free [3+3] annulation approach for the synthesis of polysubstituted pyridines via the reaction between β-enaminonitriles and β,β-dichloromethyl peroxides. This strategy operates under mild conditions, demonstrating broad substrate scope and excellent functional group tolerance. Mechanistic investigations suggest that the reaction proceeds through a Kornblum-De La Mare rearrangement followed by SV-type C-Cl bond cleavage and intramolecular cyclization/condensation. By circumventing the need for transition metal catalysts or radical initiators, our method offers practical utility in organic synthesis and provides a new avenue for the rapid construction of complex pyridine scaffolds.
我们的工作引入了一种简便高效的无金属[3+3]环化方法，通过β-烯胺腈与β,β-二氯甲基过氧化物之间的反应来合成多取代吡啶。该策略在温和条件下进行，展现出广泛的底物范围和出色的官能团耐受性。机理研究表明，反应通过Kornblum-De La Mare重排，随后进行SV型C-Cl键裂解和分子内环化/缩合。通过避免使用过渡金属催化剂或自由基引发剂，我们的方法在有机合成中具有实际应用价值，并为快速构建复杂吡啶骨架提供了一条新途径。
