胺化
亲核取代
化学
替代(逻辑)
氢
组合化学
取代反应
有机化学
催化作用
计算机科学
程序设计语言
作者
Hoonchul Choi,Won Seok Ham,Pit van Bonn,Jianbo Zhang,Dongwook Kim,Sukbok Chang
标识
DOI:10.1002/anie.202401388
摘要
The development of site‐selective functionalization of N‐heteroarenes is highly desirable in streamlined synthesis. In this context, direct amination of pyridines stands as an important synthetic methodology, with particular emphasis on accessing 4‐aminopyridines, a versatile pharmacophore in medicinal chemistry. Herein, we report a reaction manifold for the C4‐selective amination of pyridines by employing nucleophilic substitution of hydrogen (SNH). Through 4‐pyridyl pyridinium salt intermediates, 4‐aminopyridine products are obtained in reaction with aqueous ammonia without intermediate isolation. The notable regioselectivity was achieved by the electronic tuning of the external pyridine reagents along with maximization of polarizability in the proton elimination stage. Further mechanistic investigations provided a guiding principle for the selective C–H pyridination of additional N‐heteroarenes, presenting a strategic avenue for installation of diverse functional groups.
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