Ir(III) nitrene cascade turns tetrasubstituted alkenes into δ-lactams

Researchers at the State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University (Tianjin, China), have described a way to convert sterically congested tetrasubstituted alkenes into cycloalkane-fused δ-lactams. The work was published on 4 November 2026 in Nature Communications; the corresponding author is Hao Wang. doi.org

Transition-metal-catalyzed nitrene transfer is an established strategy for alkene functionalization. According to the authors, its use on tetrasubstituted alkenes has remained severely underdeveloped. doi.org

Ir(III)-catalyzed cascade

The team reports an Ir(III)-catalyzed aziridination–rearrangement cascade triggered by a nitrene. It converts cyclic-substituted tetrasubstituted alkenes into cycloalkane-fused δ-lactams. doi.org

The reaction runs under mild conditions. The authors report excellent yields and uniformly high diastereoselectivities. doi.org

The method is compatible with carbon-, oxygen- and nitrogen-based nucleophiles. According to the authors, the substrates include structurally complex and biologically relevant ones. doi.org

Mechanism: aziridination and aza-semipinacol rearrangement

Experimental and computational studies, the authors say, support the following sequence. An Ir–nitrenoid performs a concerted aziridination of the alkene and generates a strained tricyclic intermediate. doi.org

This intermediate then undergoes an aza-semipinacol rearrangement driven by strain release. The rearrangement gives a bicyclic azacarbocation. doi.org

The azacarbocation can be intercepted by a nucleophile or can undergo elimination. These two routes lead to structurally diverse fused δ-lactam architectures, and the authors describe the access as rapid. doi.org

The authors present the result as a nitrene-triggered carbocationic rearrangement manifold for functionalizing tetrasubstituted alkenes. They state that it expands the synthetic potential of transition-metal-catalyzed nitrene transfer. doi.org

The study is a synthetic-chemistry method developed in the laboratory. The material does not describe applications of the products.

Nankai University chemists convert tetrasubstituted alkenes into fused δ-lactams with an Ir(III) catalyst

Ir(III)-catalyzed cascade

Mechanism: aziridination and aza-semipinacol rearrangement

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