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Updated: Jul 24, 2025

Preparation of Contiguous Bisaziridines for Regioselective Ring-Opening Reactions
Published on: July 28, 2022
[3+2]-Cycloaddition Reactions of gem-Difluorocyclopropenes with Azomethine Ylides - Access to Novel Fluorinated
Kian Donnelly1, Amritpal Singh2, Tell Tuttle2
1School of Chemistry, University College Dublin, Belfield, D04 N2E2, Ireland.
Abstract:
The introduction of fluorinated moieties into drugs as well as the increase of their overall three-dimensionality have become key strategies amongst medicinal chemists to generate sets of compounds with favorable drug-like properties. However, the introduction of fluorinated cyclopropane ring systems which combines both strategies is not widely exploited to date. This paper reports synthetic strategies exploiting the reactivity of gem-difluorocyclopropenes in dipolar cycloaddition reactions with azomethine ylides to afford sets of new fluorine-containing 3-azabicyclo[3.1.0]hexanes. In addition, the unexpected formation of complex trifluorinated scaffolds arising from proline esters and gem-difluorocyclopropenes is highlighted along with computational studies to elucidate the underlying mechanism. This study presents new avenues towards pharmaceutically relevant fluorinated 3-azabicyclo[3.1.0]hexanes that are accessible via robust and short synthetic sequences.
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