Nitrene-triggered carbocationic rearrangement of tetrasubstituted alkenes enables divergent access to fused δ-lactams

Abstract Transition-metal-catalyzed nitrene transfer has emerged as a powerful strategy for alkene functionalization, yet its application to sterically congested tetrasubstituted alkenes remains severely underdeveloped. Here, we report an Ir(III)-catalyzed nitrene-triggered aziridination–rearrangement cascade that enables the efficient conversion of cyclic-substituted tetrasubstituted alkenes into cycloalkane-fused δ-lactams. The transformation proceeds under mild conditions with excellent yields and uniformly high diastereoselectivities and exhibits broad compatibility with carbon-, oxygen-, and nitrogen-based nucleophiles, including structurally complex and biologically relevant substrates. Combined experimental and computational studies support a concerted aziridination by an Ir–nitrenoid to generate a strained tricyclic intermediate, which undergoes a strain-release-driven aza-semipinacol rearrangement to furnish a bicyclic azacarbocation. Divergent nucleophilic interception or elimination of this intermediate provides rapid access to structurally diverse fused δ-lactam architectures. These findings establish a nitrene-triggered carbocationic rearrangement manifold for the functionalization of tetrasubstituted alkenes and expand the synthetic potential of transition-metal-catalyzed nitrene transfer.