Factors Influencing the Product Selectivity of Rh₂(OAc)₄-Catalyzed Reactions of Diazoketones with Aziridines

Rigid bicyclic aziridines enable the stereoselective formation of aziridinium ylides that lead to diverse <i>N</i>-heterocycles, but their ring strain can have a significant impact on their reactivity and product outcomes. In this study, we investigate the mechanism of Rh₂(OAc)₄-catalyzed reactions between diazoketones and aziridines using DFT calculations, focusing on how substituents on diazoketone affect product selectivity. Four possible products were examined: [3,9]-fused-ring aziridine, [6,6]-fused-ring oxazine, [6,7]-fused-ring oxazine, and ring-opened products. Our results reveal that the [3,9]-fused-ring aziridine is the kinetic product, while the desired [6,7]-fused-ring oxazine product was found to be kinetically inaccessible. Product selectivity was primarily determined by the ease of conversion of the intermediate aziridinium ylide to other products. These insights provide a mechanistic framework for controlling product formation in aziridine-based transformations.