Batch vs Continuous-Flow Method to Synthesize N-(3-acylamidopropyl)lactams through N-C Bond Cleavage in Amides with Amidines

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.