The Barbier‐Type Allylation/Lactamization Cascade Route to Isoindolinones and the Heck‐Type Annulation Route to Isoindolo[2,1‐ a ]quinolines

In this paper, we report the construction of pharmacologically relevant isoindolinones and isoindolo[2,1‐ a ]quinolines through the Zn‐mediated Barbier‐type allylation/lactamization sequential reactions and intramolecular Heck annulation reactions, respectively. The Zn‐mediated Barbier‐type allylation/lactamization sequential reactions of imine systems derived from alkyl 2‐formylbenzoates afforded a library of N ‐substituted 3‐allyl‐isoindolinone scaffolds. Then, this route was applied to assemble various N ‐(2‐haloaryl)‐3‐allyl‐isoindolinone derivatives, which were subsequently subjected to the Pd‐catalyzed intramolecular Heck‐type annulation reaction to afford the corresponding isoindolo[2,1‐ a ]quinoline frameworks. We have shown a formal synthesis of the bio‐active isoindolo[2,1‐ a ]quinoline system 1 g by synthesizing the dione system 12 , which was an intermediate in the Ishihara's scheme pertaining to the synthesis of the bio‐active isoindolo[2,1‐ a ]quinoline system 1 g .