Synthesis of S-Glycosides via Cross-Coupling Reactions

Abstract

Thioglycosides (S-glycosides) are an important class of sulfur-linked carbohydrate derivatives with widespread applications in carbohydrate synthesis and medicinal chemistry. Their enhanced hydrolytic stability and distinctive electronic characteristics, resulting from the replacement of the anomeric oxygen with sulfur, lead to altered biological recognition and make them attractive synthetic targets. Traditional methods for thioglycoside synthesis, however, often rely on harsh reaction conditions and suffer from limited stereocontrol and poor functional-group tolerance. The emergence of 1-thiosugars as stable and highly nucleophilic synthons has transformed the field, enabling mild, efficient, and versatile construction of thioglycosides through transition-metal-mediated cross-coupling reactions. This chapter provides an overview of modern strategies for synthesizing S-aryl, S-alkyl, S-alkenyl, and S-alkynyl glycosides using copper-, palladium-, and nickel-catalyzed methods. In addition, emerging approaches based on visible-light photoredox catalysis and electrochemical activation are highlighted as sustainable and powerful tools for advancing the construction of thioglycosides.