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Updated: Sep 30, 2025

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Tunable Aziridinium Ylide Reactivity: Non-covalent Interactions Enable Divergent Product Outcomes
Kate A Nicastri1, Soren Zappia1, Jared C Pratt1
1Department of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706.
Abstract:
Methods for rapid preparation of densely functionalized and stereochemically complex N-heterocyclic scaffolds are in demand for exploring potential bioactive chemical space. This work describes experimental and computational studies to better understand the features of aziridinium ylides as intermediates for the synthesis of highly substituted dehydromorpholines. The development of this chemistry has enabled the extension of aziridinium ylide chemistry to the concomitant formation of both a C-N and a C-O bond in a manner that preserves the stereochemical information embedded in the substrate. Additionally, we have uncovered several key insights that describe the importance of steric effects, rotational barriers around the C-N bond of the aziridinium ylide, and non-covalent interactions (NCIs) on the ultimate reaction outcome. These critical insights will assist in the further development of this chemistry to generate N-heterocycles that will further expand complex amine chemical space.
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