Herein, we report a strategically novel synthetic protocol for the efficient construction of α-trifluoromethyl-β-amino ketone and α-sulfonyl-β-amino ketone derivatives. 4-Isoxazoline is introduced, for the first time, as a class of effective nucleophilic SOMOphile (SOMO, single occupied molecular orbital) that readily reacts with electrophilic open-shell species such as trifluoromethyl radical and sulfonyl radical through a cascade of the homolytic addition/β-fragmentation manifold. The underlying polar effect is ascribed as the dominant factor that guarantees the cascade process both in high reaction efficiency and regioselectivity. This protocol is characterized by its mild reaction conditions and broad substrate scope, whereas the ease of acquiring enantiopure α-polyfluoroalkyl-β-amino ketone derivatives with readily accessed chiral 4-isoxazolines adds extra merit to this reaction.