An amino-assisting [3+2] cycloaddition strategy of nitrile imines generated in situ with o-aminotrifluoroacetophenones under mild conditions has been constructed, in which a variety of 1,3,4-oxadiazolines bearing CF₃-quaternary centers can be obtained in good to excellent yields. The MTT assay shows that the resulting 1,3,4-oxadiazoline derivatives could be the potential candidates for the treatments of head and neck cancers.