DOI: 10.1002/ange.202309572 ISSN:
Direct Acylation of Unactivated Alkyl Halides with Aldehydes through N‐Heterocyclic Carbene Organocatalysis
Qing‐Zhu Li, Rong Zeng, Peng‐Shuai Xu, Xin‐Hang Jin, Chuan Xie, Qi‐Chun Yang, Xiang Zhang, Jun‐Long Li- General Medicine
Abstract
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.