Feng Lili, Ni Shao-Fei, Lai Yunfei, Zhang Xiaoying, Lu Zheng-Xuan, Xiong Heng-Ying, Zhang Guangwu, Wang Teng
College of Chemistry and Chemical Engineering, Henan University, Kaifeng, Henan 475004, China.
Department of Chemistry, Shantou University, Shantou, Guangdong 515063, China.
Precis Chem. 2025 Jun 5;3(7):365-371. doi: 10.1021/prechem.5c00037. eCollection 2025 Jul 28.
Six-membered -heterocycles, such as 2-pyridones, are crucial in bioactive compounds and prevalent in natural products and pharmaceuticals, necessitating innovative synthesis approaches. Traditional methods, typically reliant on the transition-metal-catalyzed direct cyclization of alkynes, face limitations in product complexity. This study introduces a [1 + 2 + 3] annulation strategy for synthesizing 2-pyridones, employing anilines and CF-ynones through a base-promoted metal-free catalytic system. This method offers a more streamlined approach to generating polysubstituted 2-pyridones, demonstrating enhanced functional group compatibility across substrates compared with existing transformations. The anilines' adjacent dialkyl amino groups significantly contribute to the reaction, serving as both proton reservoirs and directing groups, facilitating the formation of 2-pyridones. This reaction involves a ring closure/opening sequence, followed by aza-6π-electrocyclization and a C-C bond cleavage-driven aromatization process. The method's synthetic utility is further validated by its applicability in subsequent transformations, marking an advancement in the synthesis of complex -heterocyclic compounds.
六元杂环，如2-吡啶酮，在生物活性化合物中至关重要，在天然产物和药物中普遍存在，因此需要创新的合成方法。传统方法通常依赖于过渡金属催化的炔烃直接环化，在产物复杂性方面存在局限性。本研究介绍了一种通过碱促进的无金属催化体系，利用苯胺和CF-炔酮合成2-吡啶酮的[1 + 2 + 3]环化策略。该方法为生成多取代2-吡啶酮提供了一种更简化的途径，与现有转化相比，在底物间展现出更强的官能团兼容性。苯胺的邻位二烷基氨基对反应有显著贡献，既作为质子库又作为导向基团，促进了2-吡啶酮的形成。该反应涉及一个闭环/开环序列，随后是氮杂-6π-电环化和由碳-碳键断裂驱动的芳构化过程。该方法在后续转化中的适用性进一步验证了其合成效用，标志着复杂杂环化合物合成方面的一项进展。
