1- and 2-Azetines via Visible Light-Mediated [2 + 2]-Cycloadditions of Alkynes and Oximes

J Am Chem Soc. 2021 Oct 6;143(39):16235-16242. doi: 10.1021/jacs.1c07523. Epub 2021 Sep 27.

Abstract

Azetines, four-membered unsaturated nitrogen-containing heterocycles, hold great potential for drug design and development but remain underexplored due to challenges associated with their synthesis. We report an efficient, visible light-mediated approach toward 1- and 2-azetines relying on alkynes and the unique triplet state reactivity of oximes, specifically 2-isoxazolines. While 2-azetine products are accessible upon intermolecular [2 + 2]-cycloaddition via triplet energy transfer from a commercially available iridium photocatalyst, the selective formation of 1-azetines proceeds upon a second, consecutive, energy transfer process. Mechanistic studies are consistent with a stepwise reaction mechanism via N-O bond homolysis following the second energy transfer event to result in the formation of 1-azetine products. Characteristic for this method is its operational simplicity, mild conditions, and modular approach that allow for the synthesis of functionalized azetines and tetrahydrofurans (via in situ hydrolysis) from readily available precursors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry*
  • Azetines / chemical synthesis*
  • Cycloaddition Reaction / methods*
  • Light
  • Molecular Structure
  • Oximes / chemistry*
  • Photochemical Processes*

Substances

  • Alkynes
  • Azetines
  • Oximes