Tunable aziridinium ylide reactivity: non-covalent interactions enable divergent product outcomes

26 November 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Methods for rapid preparation of densely functionalized and stereochemically complex N-heterocyclic scaffolds are in demand for exploring potential new 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. The chemistry is tolerant of a wide range of functionalities that can be employed for DNA-encoded library (DEL) synthesis to prepare diverse libraries of heterocycles with potential bioactivity. In addition, 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 novel and complex N-heterocycles that will further expand complex amine chemical space.


aziridinium ylide
non-covalent interactions

Supplementary materials

SI for Tunable aziridinium ylide reactivity: non-covalent interactions enable divergent product outcomes
Experimental procedures and spectroscopic data for all new compounds.


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