Synthesis of 3-Acyl-isoxazoles and Δ²-Isoxazolines from Methyl Ketones, Alkynes or Alkenes, and <i>tert</i>-Butyl Nitrite via a Csp³–H Radical Functionalization/Cycloaddition Cascade

Abstract

A novel metal-free tandem Csp³-H bond functionalization of ketones and 1,3-dipolar cycloaddition has been developed. An efficient approach to a variety of oxazole and isoxazoline derivatives is demonstrated using the 1,3-dipolar cycloaddition of alkynes and alkenes to nitrile oxides generated by reactions of methyl ketones with tert-butyl nitrite. This new protocol provides access to a variety of isoxazolines with diverse functionalities. An isoxazole generated in this way was found to have significant antifungal activity.