Development of a copper(II)-catalyzed three-component tandem synthesis of isoindolinone derivatives

Isoindolinone derivatives are important pharmaceutical building blocks in medicinal chemistry. Isoindolo[2,1-a]quinolines are a class of interesting compounds that possess protective effects against N ₂-induced hypoxia and inhibitory activities against human topoisomerase II and bacterial DNA-gyrase. The conventional methods for synthesizing these compounds are unsatisfactory because of their harsh reaction conditions, complex starting materials, and multistaged purification procedures. This synthesis of the propargyl-isoindolinone core features an aldehyde-alkyne-amine (A ³) coupling-based tandem strategy using methyl 2-formylbenzoate, primary aryl amine, and terminal alkyne under Cu(OTf) ₂ catalysis.