Glycosyl Triazole Based Pyridinamide/CuI-Catalyzed Coupling of 2-Halobenzamides with Active Methylene Compounds

Abstract

This report describes a convenient method for the Cu(I)- catalyzed tandem synthesis of dihydrophenanthridinediones and substituted isoquinolinones with the assistance of efficient glycosyl 1,2,3-triazole-based pyridinamide ligands. The catalytic system effectively works for the coupling of N-substituted 2-halobenzamides with various active methylene compounds to form biologically relevant heterocyclic scaffolds in high to excellent yields. The consecutive path of the reaction including intermolecular C C cross-coupling followed by intramolecular cyclization efficiently takes place at low catalytic loading. These glycosyl triazole-appended pyridinamides were synthesized in good yields by a CuI/DIPEA-mediated regioselective CuAAC click reaction. The notable features of the method include low catalytic loading, the use of cost-effective and biocompatible ligands, high reaction yield, and easily accessible starting materials that make the protocol more versatile. © 2023 Georg Thieme Verlag. All rights reserved.