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 pi -bond, and this was followed by reaction o f the in situ generated acyl chloride with 3,4-dimethoxyphenethyl amine. Th e silicon-induced Pummerer reaction of these amidosulfoxides was carried ou t 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 fo rmation of 2-thiophenyl substituted lactams. Iminium ion-aromatic pi -cycli zation was accomplished by treatment of the initially formed thiophenyl lac tams with BF3.2AcOH which resulted in the generation of an N-acyliminium io n. Cyclization of the iminium ion onto the tethered aromatic ring led to va rious azapolycyclic ring systems. A related cyclization sequence also occur red with amidosulfoxides that possess simple olefinic tethers. The method w as applied toward the synthesis of a member of the protoberberine alkaloid family. (C) 2000 Elsevier Science Ltd. All rights reserved.