School of Pharmaceutical Science and Technology, Tianjin University, 92 Weijin Road, Nankai District, Tianjin 300072, China.
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, China.
Org Biomol Chem. 2022 Feb 16;20(7):1339-1359. doi: 10.1039/d1ob02146j.
N-Heterocycles can be found in natural products and drug molecules and are indispensable components in the area of organic synthesis, medicinal chemistry and materials science. The construction of these N-containing heterocycles by traditional methods usually requires the preparation of reactive intermediates. In the past decades, with the rapid growth of transition metal catalysed coupling reactions, syntheses of heterocycles from precursors with inert chemical bonds have become a challenge. More recently, in the field of transition metal associated C-H direct functionalization, efficient methods have been developed for the syntheses of N-heterocyclic compounds such as aziridines, azetidines, indoles and quinolines under the click type of reaction mode. In this review, representative synthetic methodologies developed in the recent 10 years for the preparation of this small class of N-heterocycles the Pd-catalysed C-H activation and C-N bond formation pathway are discussed. We hope this article will provide new insights from the strategies highlighted into future molecular design, synthesis and applications in medical and materials sciences.
杂环化合物存在于天然产物和药物分子中，是有机合成、药物化学和材料科学领域不可或缺的组成部分。传统方法构建这些含氮杂环化合物通常需要制备反应性中间体。在过去的几十年中，随着过渡金属催化偶联反应的快速发展，从具有惰性化学键的前体合成杂环化合物已成为一项挑战。最近，在过渡金属相关的 C-H 直接官能化领域，已经开发出了在点击反应模式下高效合成氮杂环化合物（如氮丙啶、氮杂环丁烷、吲哚和喹啉）的方法。在本文中，我们讨论了近 10 年来发展起来的用于制备这一小类氮杂环化合物的代表性合成方法学，即钯催化的 C-H 活化和 C-N 键形成途径。我们希望本文能够从所强调的策略中为未来的分子设计、合成以及在医学和材料科学中的应用提供新的见解。
