Metal-free and VOC-free O-glycosylation in supercritical CO2

Abstract

Supercritical carbon dioxide (scCO₂) is a suitable medium to perform transition metal-free glycosylation reactions in the absence of volatile organic solvents (VOCs) using glycosyl halides as glycosyl donors. The methodology described here can be applied for obtaining O-glycosides in a totally green reaction, as well as orthoesters, depending on the reaction conditions. The process is much more sensitive to temperature changes than to pressure modification, with glycosyl chlorides requiring higher temperatures to be activated than glycosyl bromides. Pivaloyl groups act as good CO₂-philic units and are shown to be the best choice to obtain good stereoselectivities. The relevance of the fluid nature and supercritical conditions was also evidenced.