Tunable Aziridinium Ylide Reactivity: Noncovalent Interactions Enable Divergent Product Outcomes

Methods for rapid preparation of densely functionalized and stereochemically complex N-heterocyclic scaffolds are in demand for exploring the 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 C–O bond in a manner that preserves 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 noncovalent interactions on the ultimate reaction outcome. These critical insights will assist in the development of this chemistry to generate N-heterocycles that will further expand the complex amine chemical space.