Photoinduced, Pd-Catalyzed Glycosyl Three-Component Reaction: Access to C -Alkyl Glycoside via 1,4-Glycosylamination of 1,3-Butadiene

Abstract

The synthesis of diverse functionalized carbohydrate derivatives holds great importance for advancing carbohydrate-based drug development. By integrating an atom-economic multicomponent reaction (MCR) strategy, in this work, we report a visible-light-induced, palladium-catalyzed radical three-component reaction involving glycosyl halides, achieving efficient access to C-alkyl glycosides containing a crotonamide scaffold. Moreover, starting directly from glycosyl hemiacetal, the same MCR transformation was achieved in a convenient, one-pot procedure. Leveraging the highly efficient radical trapping ability of 1,3-butadiene, this approach demonstrates broad substrate compatibility across a diverse range of carbohydrate substrates and various aliphatic amine partners including several approved drug molecules containing amine functional groups.