Regioselective Chalcogenation of Glycals: DBU and Iodine-Mediated, Transition-Metal-Free Synthesis of Heteroaryl Thio- and Seleno-Glycoconjugates

Abstract

We report a transition-metal-free approach of regioselective C-2 chalcogenation of glycals, employing 2-thio- and 2-selenocyanato-glycals as chalcogen sources. Synergistic combination of DBU and catalytic iodine promotes the in-situ generation of disulfenyl glycal intermediate, which on selective nucleophilic interception by heteroarenes, delivers the thio- and seleno-glycoconjugates in appreciable yields. This protocol exhibits promising substrate tolerance, accommodating imidazo[1,2-a]pyridines, indoles, azaindoles, imidazo[2,1-b]thiazoles, and benzo[d]imidazo[2,1-b]thiazoles bearing electron-rich and electron-deficient substituents. This sustainable transformation offers a platform for constructing chalcogen-linked carbohydrate frameworks, addressing the synthetic challenge of glycoscience and medicinal chemistry.