Four-Component Reactions for the Synthesis of Perfluoroalkyl Isoxazoles

A four-component strategy for the synthesis of the isoxazole skeleton is developed. The approach achieves the synthesis of perfluoroalkyl isoxazoles by using simple perfluoroalkyl reagents. In addition, the unprecedented 3-azido-5-arylisoxazole formation demonstrates Togni’s reagent as a C-1 unit to be used in the isoxazole formation. The advantages of the method include readily available starting materials, structural diversity, and late-stage functionalization. Mechanistic studies support that the transformation includes a tandem process of perfluoroalkylation–peroxidation of alkene, Kornblum–DeLaMare rearrangement, elimination, substitution, and N–O bond formation to give the isoxazoles.