The Thionium/N-Acyliminium Ion Cyclization Cascade as a Strategy for the Synthesis of Azapolycyclic Ring Systems

A series of amidosulfoxides were prepared by the addition of thiophenol to the appropriate alkenoic acid π-bond, and this was followed by reaction of the in situ generated acyl chloride with 3,4-dimethoxyphenethyl amine. The silicon-induced Pummerer reaction of these amidosulfoxides was carried out using 1-(dimethyl-tert-butylsiloxy)-1-methoxyethylene in dry acetonitrile in the presence of a catalytic amount of ZnI2 and led to the very clean formation of 2-thiophenyl substituted lactams. Iminium ion-aromatic π-cyclization was accomplished by treatment of the initially formed thiophenyl lactams with BF3·2AcOH which resulted in the generation of an N-acyliminium ion. Cyclization of the iminium ion onto the tethered aromatic ring led to various azapolycyclic ring systems. A related cyclization sequence also occurred with amidosulfoxides that possess simple olefinic tethers. The method was applied toward the synthesis of a member of the protoberberine alkaloid family.