Synthesis of 3-Methyleneisoindolin-1-ones and Isoquinolinium Salts via Exo and Endo Selective Cyclization of 2-(1-Alkynyl)benzaldimines

Coinage metal-promoted 5-exo and 6-endo selective cyclization of 2-(1-alkynyl)benzaldimines has been studied. It was found that, under gold catalysis, 2-(1-alkynyl)benzaldimines exclusively underwent 5-exo-dig cyclization processes, followed by oxidation to form N-aryl 3-methyleneisoindolin-1-ones. In contrast, in the presence of base and under activation of AgOTf, switching of 5-exo to 6-endo cyclizations of 2-(1-alkynyl)benzaldimines was observed, exclusively giving N-aryl or N-alkyl substituted isoquinolinium salts. The two key reaction intermediates, exocyclic vinyl-Au and the endocyclic vinyl-Ag species have been isolated and characterized, and a study of their reactivities confirms the plausible mechanisms. Reactions of the resultant 3-methyleneisoindolin-1-ones with benzyne afforded structurally important isoindolinone-based benzocyclobutenes. Additionally, several interesting transformations of the resultant isoquinolinium salts have been investigated.