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

Abstract

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.