Oxidized isoquinolinoisoindolinone and benzazepinoisoindolinone alkaloids cores by convergent cyclisation processes: π-aromatic attack of thionium and oxonium species

Abstract

An efficient methodology for synthesis of isoindoloisoquinoline 5a and isoindolobenzazepine 5b in oxidized forms as tetracyclic alkaloids cores are reported from N-bromoethylphthalimide (6) or phthalic anhydride and 2-phenylthioethylamine (8) in a five- or six-step sequence, respectively, in overall very good yields. The key step of this methodology is based on an intramolecular π-cationic cyclization of the thionium ion species. Alternatively, another four-step route was explored and based in an ultimate step on the cyclodehydration of an aldehyde functionality, which used as intermediate in the latest strategy, via the oxonium ion cation.