A Multicomponent Strategy With Amines, Aldehydes, Carboxylic Acids, and Nucleophiles: A Modular Access to N ‐α‐Functionalized Amides

N ‐α‐functionalized amides are important structural motifs in drug discovery and organic synthesis. However, the direct and efficient multicomponent synthesis of N ‐α‐functionalized amides remains highly challenging. Herein, we report a novel N ‐acyliminium‐based four‐component reaction employing amines, aldehydes, carboxylic acids, and nucleophiles, which enables access to N ‐α‐functionalized amides with molecular diversity. This multicomponent reaction is characterized by the use of readily available starting materials, high atom and step economy, and operational simplicity. It also exhibits a good substrate scope and high functional group tolerance. The practical value of this method is highlighted by its utility in the facile synthesis of valuable bioactive molecules and the late‐stage functionalization of pharmaceuticals and complex compounds. Mechanistic studies revealed that the preferential reaction between aldehydes and amines is key to the success of this four‐component reaction.