Wu Jiahao, Tan Xiangwen, Wu Wanqing, Jiang Huanfeng
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510641, China.
Nat Commun. 2024 Aug 8;15(1):6776. doi: 10.1038/s41467-024-51173-4.
Palladium catalyzed tandem reaction represents a one-pot synthetic approach to efficiently synthesize complex functionalized molecules while reducing synthetic steps, aligning with the principles of green chemistry. However, achieving a direct cascade of the aza-Wacker and Povarov reactions in one-pot synthesis presents a challenge due to substrate compatibility issues between the two reactions. In this work, we describe an aza-Wacker/Povarov reaction employing a highly electrophilic palladium catalyst, which effectively converts anilines and 1,6-dienes into hexahydro-cyclopenta[b]quinolines. The optimized conditions yield up to 79%, with a diastereoselectivity > 20:1. Substrate range testing reveals compatibility with various sensitive functional groups, and successful late-stage modifications are performed on several natural products and drug molecules, demonstrating the versatility and practicality of the method. Additionally, a preliminary investigation into the reaction mechanism suggests an aza-Wacker process followed by a Povarov process.
钯催化串联反应是一种一锅法合成方法，能够在减少合成步骤的同时高效合成复杂的功能化分子，符合绿色化学的原则。然而，由于这两个反应之间的底物兼容性问题，在一锅合成中实现氮杂瓦克反应和波瓦罗夫反应的直接串联具有挑战性。在这项工作中，我们描述了一种使用高亲电钯催化剂的氮杂瓦克/波瓦罗夫反应，该反应能有效地将苯胺和1,6-二烯转化为六氢环戊并[b]喹啉。优化后的条件产率高达79%，非对映选择性大于20:1。底物范围测试表明该反应与各种敏感官能团具有兼容性，并且在几种天然产物和药物分子上成功进行了后期修饰，证明了该方法的通用性和实用性。此外，对反应机理的初步研究表明，反应过程为先进行氮杂瓦克反应，然后进行波瓦罗夫反应。
