Reductive Coupling of Carbonyl Compounds with Primary Amides for the Synthesis of N -Alkyl Amides

The construction of N-alkyl amides from readily available feedstocks represents an attractive strategy for facile and sustainable synthesis. The N-alkylation of primary amides with aldehydes or ketones provides an available protocol. However, this method remains challenging because of the low nucleophilicity of amides and the need for metal reagents. Herein, we report a metal-free reductive protocol that enables the direct coupling of primary amides with aldehydes or ketones. The reaction has features such as operational simplicity, good functional group tolerance, high yields, and scalability, making it suitable for practical synthesis and providing efficient access to a broad range of N-alkyl amides.