Three-Component Reactions to Spirocyclic Pyrrolidinonylformimidamides: alpha-Isocyano Lactams as Two-Atom Unit in Silver-Catalyzed Formal [3+2] Cycloaddition Reactions

A facile approach to spirocyclic pyrrolidinonylformimidamides has been developed via three-component reactions of isocyanides, alkenes, and amines. The reaction proceeds through a sequence of two distinct reaction pathways; the base-catalyzed conjugate addition of alpha-isocyano lactams to electron-deficient alkenes and the Ag(I)-catalyzed amine insertion to the isocyanide moiety. Both reactions display markedly different reaction kinetics, allowing the one-pot three-component reactions to be performed in the presence of respective catalysts, a Bronsted base and a silver salt. The formation of spirocyclic pyrrolidin-2-ones represents an unusual use of alpha-isocyano lactam as a two-atom unit in a formal [3 + 2] cycloaddition reaction. The successful identification of ways to defy the typical three-atom unit role of alpha-isocyano carbonyl compounds in the [3 + 2] cycloaddition pathways manifests a rapid assembly of medicinally important spirocyclic scaffolds from readily available starting materials.