ADDITIVE AND VINYLOGOUS PUMMERER REACTIONS OF AMIDO SULFOXIDES AND THEIR USE IN THE PREPARATION OF NITROGEN-CONTAINING HETEROCYCLES

The alpha-thiocarbocation generated from the Pummerer re action of N-p henyl-2-[2-(toluene-4-sulfinyl)phenyl]acetamide undergoes Friedel-Craf ts reaction at the gamma-carbon with the tethered aromatic ring. Reduc tive removal of the phenylthio group from the resulting product using Raney nickel occurs in high yield, and the overall reaction represents a new method for the synthesis of a variety of 3-phenyl-substituted o xindoles. Treatment of the related N-benzyl-N-alkyl amido sulfoxide sy stem with trifluoroacetic anhydride affords tetrahydroisoquinolone der ivatives. The product distribution encountered coincides with the rota mer population of the starting amide. When the N-benzyl-N-methyl amide is used, only the normal Pummerer product is formed. In this case, th e thionium ion is generated in the wrong conformation for pi-cyclizati on to occur. The corresponding N-tert-butyl amido system, however, exi sts in a geometric orientation which places the benzylic group in the crucial conformation necessary for pi-cyclization, and consequently, t he reaction proceeds smoothly. Related cyclization reactions occur in good yield with the corresponding furanyl and cyclohexenyl N-tert-buty l amido sulfoxides. The additive Pummerer reaction of 3-phenylsulfinyl -N-benzyl-N-tert-butylacrylamide gave products derived from both 5- an d 6-exo trig cyclizations. Intramolecular electrophilic aromatic subst itution via six-membered ring closure ultimately afforded a dihydropyr idone. The competitive process involving ipso attack of the aromatic r ing on the thionium ion generates a spiro cyclohexadienyl cation that undergoes fragmentation of the adjacent a-bond. The resulting acyl imi nium ion is converted to N-tert-butyl-2-phenyl-3-phenylsulfinylacrylam ide upon aqueous workup. Only cyclizations leading to five-membered ri ngs occur with the corresponding indolyl and alkenyl N-tert-butyl amid o sulfoxides.