Batch vs Continuous‐Flow Method to Synthesize N‐(3‐Acylamidopropyl)Lactams Through N−C Bond Cleavage in Amides with Amidines

Abstract

The selective N‐C bond cleavage of amides to create value‐added products through a transition metal‐free approach has become a significant challenge. Here, we present a method to convert amides into N‐(3‐acylamidopropyl)lactams through sequential amide chemoselective N‐C bond cleavage and amidine ring opening under mild conditions, applicable in batch and continuous flow processes. These methods utilize bench‐stable reagents and are operationally straightforward and mild, enabling synthesis on a gram scale with excellent functional group tolerance. Additionally, the synthetic feasibility of these reactions under flow conditions has proven to be highly efficient, providing N‐(3‐acylamidopropyl)lactam derivatives with improved yields and shorter reaction time.