TY - JOUR A1 - Gulbe, Krista A1 - Lugiņina, Jevgeņija A1 - Jansons, Edijs A1 - Kinens, Artis A1 - Turks, Māris T1 - Metal-free glycosylation with glycosyl fluorides in liquid SO2 JF - Beilstein Journal of Organic Chemistry PY - 2021/// VL - 17 SP - 964 EP - 976 SN - 1860-5397 DO - 10.3762/bjoc.17.78 PB - Beilstein-Institut JA - Beilstein J. Org. Chem. UR - https://doi.org/10.3762/bjoc.17.78 KW - fluorosulfite KW - glycosyl fluoride KW - Lewis acid KW - liquid sulfur dioxide KW - metal-free glycosylation N2 - 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. ER -