Lewis Base-Catalyzed Three-Component Reaction of Amines, Isocyanates, and Morita–Baylis–Hillman Carbonates: Access to Fully Substituted 5-Methylenedihydrouracils

We reported a Lewis base-catalyzed one-pot, two-step, multicomponent reaction of readily available primary amines, isocyanates, and Morita-Baylis-Hillman (MBH) carbonates. The transformation proceeds via a cascade S_N2'/intramolecular cyclization of an in situ-generated urea intermediate with MBH carbonates, enabling efficient access to structurally diverse, fully substituted 5-methylenedihydrouracils. This methodology features a broad substrate scope and excellent functional group tolerance. Notably, unsymmetrical <i>N</i>-aryl, <i>N</i>'-alkyl urea intermediates react with complete regioselectivity, furnishing a single isomer exclusively. The synthetic utility is further demonstrated by successful gram-scale synthesis and late-stage functionalization of the products.