Li Qing-Zhu, Zeng Rong, Xu Peng-Shuai, Jin Xin-Hang, Xie Chuan, Yang Qi-Chun, Zhang Xiang, Li Jun-Long
Anti-infective Agent Creation Engineering Research Centre of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, 610106, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Angew Chem Int Ed Engl. 2023 Oct 2;62(40):e202309572. doi: 10.1002/anie.202309572. Epub 2023 Aug 25.
Catalytic acylation of organohalides with aldehydes is an ideal strategy for the direct synthesis of ketones. However, the utilization of unactivated alkyl halides in such a transformation remains a formidable challenge. In this study, we developed a cross-coupling reaction of aldehydes with unactivated alkyl halides through N-heterocyclic carbene catalysis. With this protocol, various ketones could be rapidly synthesized from readily available starting materials under mild conditions. This organocatalytic system was successfully applied in the late-stage functionalization of pharmaceutical derivatives. Mechanistic investigations suggest a closed-shell nucleophilic substitution mechanism for this reaction.
有机卤化物与醛的催化酰化反应是直接合成酮的理想策略。然而，在这种转化中使用未活化的烷基卤化物仍然是一项艰巨的挑战。在本研究中，我们通过N-杂环卡宾催化开发了醛与未活化烷基卤化物的交叉偶联反应。通过该方案，可以在温和条件下从容易获得的起始原料快速合成各种酮。该有机催化体系已成功应用于药物衍生物的后期官能团化。机理研究表明该反应为闭壳亲核取代机理。
