Wei Siqi, Zhang Guocong, Wang Yahui, You Mengwei, Wang Yanan, Zhou Liejin, Zhang Zuxiao
Key Laboratory of the Ministry of Education for Advanced Catalysis Materials, Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua, China.
iScience. 2023 Feb 9;26(3):106137. doi: 10.1016/j.isci.2023.106137. eCollection 2023 Mar 17.
The unsaturated aza-heterocycles such as tetrahydropyridines pose significant applications in both drug discovery and development. However, the methods to construct polyfunctionalized tetrahydropyridines are still limited. Herein, we report a modular synthesis of tetrahydropyridines via copper catalyzed multicomponent radical cascade reaction. The reaction features mild conditions and broad substrate scope. In addition, the reaction could scale up to gram scale with similar yield. A variety of 1,2,5,6-tetrahydropyridines with C3 and C5 substituents could be assembled from simple starting materials. More importantly, the products could serve as versatile intermediate to access various functionalized aza-heterocycles which further demonstrates its utility.
不饱和氮杂环如四氢吡啶在药物研发中具有重要应用。然而，构建多官能化四氢吡啶的方法仍然有限。在此，我们报道了一种通过铜催化的多组分自由基串联反应模块化合成四氢吡啶的方法。该反应条件温和，底物范围广泛。此外，该反应可以放大到克级规模且产率相似。各种具有C3和C5取代基的1,2,5,6-四氢吡啶可以由简单的起始原料组装而成。更重要的是，这些产物可以作为通用中间体用于合成各种官能化氮杂环，这进一步证明了其实用性。
