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

Abstract

The report describes a convenient method for the Cu(I)-catalyzed tandem synthesis of dihydrophenanthridine-diones 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 achieve a high-to-excellent yield of biologically relevant heterocyclic scaffolds. 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 via CuI/DIPEA mediated regioselective CuAAC click tool. There are some notable features of the method, including low catalytic loading, the cost-effective and biocompatible nature of ligands, high reaction yield, and easily accessible starting materials that make the protocol more versatile.