Unlocking redox-active reactivity of dearomatized pyridines with photochemistry toward meta-C–H functionalization of pyridines

IF 11.5 Q1 CHEMISTRY, PHYSICAL

Chem Catalysis Pub Date : 2025-03-17 DOI:10.1016/j.checat.2025.101326

Mingkai Yang, Mei Wang, Haiman Zhang, Shi Qin, Manzoor Zaman, Jiayu Luo, Shiping Zhan, Xu Wang, Cheng Zhang, Shengdong Wang, Hui Gao, Zhi Zhou, A. Stephen K. Hashmi, Wei Yi, Zhongyi Zeng

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Abstract

Selective meta-C–H functionalization of pyridines is particularly attractive in synthetic and medicinal chemistry but remains largely underdeveloped due to their intrinsic electronic nature. Therefore, temporary dearomatization has gradually evolved as a powerful tool for this selective transformation. However, established methods all utilized dearomatized pyridine intermediates as redox-inert π-electron donors to react with ionic or radical-type electrophiles. Herein, the redox-active reactivity of dearomatized oxazino-pyridines is unlocked by photochemistry, providing a unified and modular platform for meta-C–H sulfonylation, sulfamoylation, and trifluoromethylation of pyridines. Integrated experimental and computational mechanistic studies revealed the concurrent generation of oxazino-pyridine radicals and sulfonyl radicals as well as their polarity-matched radical-radical couplings. This mild protocol features complete regiocontrol, remarkable functional group compatibility, and practical applicability in late-stage modification of bioactive molecules.

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用光化学技术开启脱芳烃吡啶的氧化还原活性反应，实现吡啶的元-C-H 功能化

吡啶的选择性元-C-H 功能化在合成和药物化学中尤其具有吸引力，但由于其固有的电子性质，这种功能化在很大程度上仍未得到充分发展。因此，临时脱芳烃逐渐发展成为这种选择性转化的有力工具。然而，已有的方法都是利用脱芳烃吡啶中间体作为氧化还原惰性 π 电子供体，与离子型或自由基型亲电体发生反应。在这里，脱芳烃的噁嗪基吡啶的氧化还原活性通过光化学得以释放，为吡啶的元-C-H 磺酰化、氨基磺酰化和三氟甲基化提供了一个统一的模块化平台。综合实验和计算机理研究揭示了噁嗪吡啶自由基和磺酰自由基的同时生成及其极性匹配的自由基-自由基耦合。这种温和的方法具有完全的区域控制、显著的官能团兼容性和生物活性分子后期修饰的实用性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chem Catalysis

CiteScore

10.50

自引率

6.40%

发文量

期刊介绍： Chem Catalysis is a monthly journal that publishes innovative research on fundamental and applied catalysis, providing a platform for researchers across chemistry, chemical engineering, and related fields. It serves as a premier resource for scientists and engineers in academia and industry, covering heterogeneous, homogeneous, and biocatalysis. Emphasizing transformative methods and technologies, the journal aims to advance understanding, introduce novel catalysts, and connect fundamental insights to real-world applications for societal benefit.