Ring Expansion of Bicyclic Methyleneaziridines via Concerted, Near-Barrierless [2,3]-Stevens Rearrangements of Aziridinium Ylides

Abstract

The synthesis of densely functionalized azetidinesin a highly stereocontrolled manner is challenging, but interest in the bioactivities of these small heterocycles has stimulated methods for their preparation. We recently reported a one-carbon ring expansion of bicyclic methylene aziridines under dirhodium catalysis capable of delivering enantioenriched azetidines. This work explores this ring expansion using computational and experimental studies. DFT computations indicate that the reaction proceeds through formation of an aziridinium ylide, which is precisely poised for concerted, asynchronous ring-opening/closing to deliver the azetidines in a [2,3]-Stevens-type rearrangement. The concerted nature of this rearrangement is responsible for the stereospecificity of the reaction, where axial chirality from the initial allene substrate is transferred to the azetidine product with complete fidelity. The computed mechanistic pathway highlights the key roles of the olefin and the rigid structure of the methylene aziridine in differentiating our observed ring expansion from competing cheletropic elimination pathways noted with ylides derived from typical aziridines.

Graphical Abstract