Synthesis of Substituted 2-Pyridones via the Pummerer Cyclization−Deprotonation−Cycloaddition Cascade of Imidosulfoxides

1-Ethanesulfinylacetylpiperidin-2-one was prepared from δ-valerolactam in two steps by heating with ethylsulfenylacetyl chloride followed by sodium periodate oxidation. Slow addition of the imidosulfoxide to a refluxing mixture of toluene, acetic anhydride (10 equiv), and p-toluenesulfonic acid (1 mol %) resulted in the formation of an isomünchnone dipole which underwent bimolecular trapping in good yield. The stereochemical assignment of the cycloadduct was made on the basis of X-ray crystallography and is the consequence of an endo cycloaddition with respect to the dipole. The regiochemistry of the cycloaddition is consistent with a HOMO-dipole controlled process. Several related imidosulfoxides containing a tethered alkenyl group were prepared and subjected to the Pummerer reaction conditions. The resulting mesoionic dipoles formed by the cyclization−deprotonation sequence undergo ready dipolar cycloaddition across the pendant olefin to afford intramolecular cycloadducts in high yield. Exposure of these cycloadducts to acetic anhydride in the presence of a trace of p-toluenesulfonic acid results in ring opening to give 5-acetoxy-substituted 2-pyridones. The lone pair of electrons on the amide nitrogen assists in opening the oxy bridge to generate a transient N-acyliminium ion, which subsequently loses a proton. In certain cases, the amide electron pair with the oxy bridge is partially twisted from an antiperiplanar arrangement and a competive ring cleavage also occurs to give 5-thioethyl-substituted 2-pyridones.