Cyclic sulfones play an important role in the field of drug discovery and design due to their valuable properties and their broad range of applications. Herein, we report an efficient cerium(IV)-catalyzed allylic oxidation of a simple 3-sulfolene. This process provides a straightforward and facile approach to sulfol-2-en-4-one, a versatile synthetic intermediate. Notably, this study represents the first instance of cerium catalysis employed in allylic oxidation. Furthermore, we demonstrated the transformation of sulfol-2-en-4-one into 4-substituted sulfol-2-enes with therapeutic applications. In silico analysis performed using the SwissAdme tool indicated that the obtained 4-amine (7 a-7 d) and 4-carbamate (9 a and 9 b) derivatives of sulfol-2-en-4-one met the rules imposed on small-molecule drugs. Moreover, these compounds inhibited the proliferation (MTT assay) of colon cancer and osteosarcoma cells. Notably, compounds 7 b and 7 c, which exhibited the best selectivity index (ratio of IC