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

A novel metal-free tandem Csp(3)-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 tent-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.