Metal-free glycosylation with glycosyl fluorides in liquid SO₂.

ABSTRACT: Liquid SO₂ is a polar solvent that dissolves both covalent and ionic compounds. Sulfur dioxide possesses also Lewis acid properties, including the ability to covalently bind Lewis basic fluoride ions in a relatively stable fluorosulfite anion (FSO₂ ^-). Herein we report the application of liquid SO₂ as a promoting solvent for glycosylation with glycosyl fluorides without any external additive. By using various temperature regimes, the method is applied for both armed and disarmed glucose and mannose-derived glycosyl fluorides in moderate to excellent yields. A series of pivaloyl-protected O- and S-mannosides, as well as one example of a C-mannoside, are synthesized to demonstrate the scope of the glycosyl acceptors. The formation of the fluorosulfite species during the glycosylation with glycosyl fluorides in liquid SO₂ is proved by ¹⁹F NMR spectroscopy. A sulfur dioxide-assisted glycosylation mechanism that proceeds via solvent separated ion pairs is proposed, whereas the observed α,β-selectivity is substrate-controlled and depends on the thermodynamic equilibrium.

SUBMITTER: Gulbe K 

PROVIDER: S-EPMC8093551 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature