Accessing rare α-heterocyclic aziridines via Brønsted acid-catalyzed Michael addition/annulation: scope, limitations, and mechanism

Timothy A. Hilton, Andrew Leach, Aiden P McKay, Allan J. B. Watson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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
Original languageEnglish
Article numbere202303993
JournalChemistry - A European Journal
VolumeIn press
DOIs
Publication statusAccepted/In press - 5 Feb 2024

Keywords

  • Annulation
  • Aziridine
  • Diastereoselectivity
  • Heterocycles
  • Mechanism

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