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Updated: Jul 4, 2025

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
Accessing Rare α-Heterocyclic Aziridines via Brønsted Acid-catalyzed Michael Addition/Annulation: Scope, Limitations,
Timothy A Hilton1, Andrew G Leach2, Aidan P McKay1
1EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, U.K.
Abstract:
We report an approach to the diastereoselective synthesis of 1,2-disubstituted heterocyclic aziridines. A Brønsted acid-catalyzed conjugate addition of anilines to trisubstituted heterocyclic chloroalkenes provides an intermediate 1,2-chloroamine. Diastereocontrol was found to vary significantly with solvent selection, with computational modelling confirming selective, spontaneous fragmentation in the presence of trace acids, proceeding through a pseudo-cyclic, protonated intermediate and transition state. These chloroamines can then be converted to the aziridine by treatment with LiHMDS with high stereochemical fidelity. This solvent-induced stereochemical enrichment thereby enables an efficient route to rare cis-aziridines with high dr. The scope, limitations, and mechanistic origins of selectivity are also presented.
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