Using the Pummerer cyclization-deprotonation-cycloaddition cascade of imidosulfoxides for alkaloid synthesis

The Pummerer reaction of imidosulfoxides bearing tethered alkenyl groups ha s been employed for the synthesis of several alkaloids. The required imidos ulfoxides necessary for the cascade sequence were easily obtained by heatin g the appropriate amide with (ethylsulfenyl)acetyl chloride followed by sod ium periodate oxidation. The initially formed thionium ion, obtained by tre ating the imidosulfoxide with acetic anhydride and p-toluenesulfonic acid, reacts with the neighboring imido group, and the resulting oxonium ion unde rgoes subsequent deprotonation to produce an isomunchnone dipole. This meso ionic betaine intermediate undergoes ready intramolecular dipolar cycloaddi tion across the neighboring ct-bond. Exposure of the resulting cycloadducts to additional acetic anhydride leads to ring opening and formation of a 5- acetoxy-substituted 2(1H)-pyridone. This six-ring heterocyclic system const itutes a valuable building block for the synthesis of a variety of pyridine , quinolizidine, and clavine alkaloids. The cyclization-deprotonation-cyclo addition cascade has been successfully applied to the synthesis of the natu rally occurring alkaloids onychnine, dielsiquinone, (+/-)-lupinine, (+/-)-a nagyrine, (+/-)-pumiliotoxin C, and (+/-)-costaclavine.