Shi Qiu, Huang Xiaofeng, Yang Ruizhi, Liu Wenbo H
School of Chemistry, Sun Yat-sen University Guangzhou 510006 China
Chem Sci. 2024 Jul 4;15(31):12442-12450. doi: 10.1039/d4sc03739a. eCollection 2024 Aug 7.
C-H Functionalization of pyridines is an efficient strategy to access pyridine derivatives occurring in pharmaceuticals, agrochemicals, and materials. Nucleophilic additions to pyridiniums both ionic and radical species have proven particularly useful. However, these reactions suffer from poor regioselectivity. By identifying an enzyme-mimic pocket-type urea activation reagent, we report a general platform for pyridine C-4 functionalization. Both ionic and radical nucleophiles can be incorporated to achieve the alkylation and arylation. Notably, the highly regioselective C-4 radical arylation is disclosed for the first time. The broad scope of nucleophiles and pyridines renders this platform applicable to the late-stage functionalization of drug-like molecules and the preparation of complex biologically important molecules.
吡啶的C-H官能团化是一种获得存在于药物、农用化学品和材料中的吡啶衍生物的有效策略。事实证明，对吡啶鎓盐进行亲核加成（包括离子型和自由基型物种）特别有用。然而，这些反应的区域选择性较差。通过鉴定一种模拟酶口袋型尿素活化试剂，我们报道了一个用于吡啶C-4官能团化的通用平台。离子型和自由基型亲核试剂都可以引入以实现烷基化和芳基化。值得注意的是，首次公开了高度区域选择性的C-4自由基芳基化反应。亲核试剂和吡啶的广泛范围使得该平台适用于类药物分子的后期官能团化以及复杂生物重要分子的制备。
