Investigating the stereo-directing effect of remote participating groups on selectivity in the 2-deoxyglycosylation of galactal†

Abstract

Chemical glycosylation is arguably crucial for assembling the structurally defined polysaccharides and glycoconjugates of distinctive biological functions. Predicting and governing the stereochemical outcome in the glycosylation reaction is undoubtedly more challenging and influenced mainly by the configuration of protecting groups (PGs) and ring conformers. In this paper, we exploited the direct influence of stereoelectronically diverse PGs on the anomeric selectivity in 2-deoxyglycosylation. The galactal donors with C-4 O-pivaloyl as a higher electron density group ensured enhanced α-selectivity; practically, trichloroacetimidate (O-TCA) ensured optimal selectivity, affirming the covalent remote group participation (RGP) featuring distinctive ring-bridging oxazepine structures. Mechanistic investigations employing density functional theory (DFT) and experimental studies revealed the perspective of RGP by distal C-4 PGs, which facilitate the stabilization of ⁴H₃ and ³H₄ conformations of oxocarbenium ions via dioxolenium species.