1,2-Aryl Migration Induced by Amide C-N Bond-Formation: Reaction of Alkyl Aryl Ketones with Primary Amines Towards α,α-Diaryl β,γ-Unsaturated γ-Lactams

Rearrangement reactions incorporated into cascade reactions play an important role in rapidly increasing molecular complexity from readily available starting materials. Reported here is a Cu-catalyzed cascade reaction of alpha-(hetero)aryl-substituted alkyl (hetero)aryl ketones with primary amines that incorporates an unusual 1,2-aryl migration induced by amide C-N bond formation to produce a class of structurally novel alpha,alpha-diaryl beta,gamma-unsaturated gamma-lactams in generally good-to-excellent yields. This cascade reaction has a broad substrate scope with respect to primary amines, allows a wide spectrum of (hetero)aryl groups to smoothly undergo 1,2-migration, and tolerates electronically diverse alpha-substituents on the (hetero)aryl ring of the ketones. Mechanistically, this 1,2-aryl migration may stem from the intramolecular amide C-N bond formation which induces nucleophilic migration of the aryl group from the acyl carbon center to the electrophilic carbon center that is conjugated with the resulting iminium moiety.

Automated summary

In this study, a copper-catalyzed cascade reaction was reported, which produced novel γ-lactams through 1,2-aryl migration with a broad substrate scope and high yields. Mechanistically, the 1,2-aryl migration may be derived from the intramolecular amide C-N bond formation.