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.

Facile synthesis of sulfonyl fluorides from sulfonic acids

“…Heating a solution of thionyl fluoride dissolved in DMF to 130 °C resulted in the formation of FSO 2 − , indicated by a signal at +36 ppm by 19 F NMR spectroscopy. 22 The presence of FSO 2 − confirmed that deoxygenation of DMF was occurring within our reaction system forming either compound 5 or 7 (Scheme 2a).…”

“…Heating a solution of thionyl fluoride dissolved in DMF to 130 1C resulted in the formation of FSO 2 À , indicated by a signal at +36 ppm by 19 F NMR spectroscopy. 22 The presence of Yields determined by 19 F NMR spectroscopy at 0.25 mmol. a Equivalents of thionyl fluoride gas dissolved in DMF.…”

Desulfonative Suzuki–Miyaura Coupling of Sulfonyl Fluorides

“…À as the only compounds visible by 11 B NMR. 19 F NMR of the same extracts confirmed the presence of these species along with a small amount of SO 2 F À [41] and other unidentified peaks. HRMS analysis confirmed the presence of fluorosulfite ions and several several fluoroborates (BF(OH) 3 À , BF 2 (OH) 2 À , BF 3 (OH) À , BF 4…”

Vessel effects in organic chemical reactions; a century-old, overlooked phenomenon

“…Turks and co-workers have recently identified SO 2 as both a solvent and as an activator of glycosyl fluorides, 64 which also gave rise to the discovery of a remarkable vessel effect. Whereas mannosylations proceeded in high yields at 100 °C in SO 2 , a comparable experiment in a PTFE vessel only resulted in 8% yield of the desired product and recovery of 53% of the electrophile.…”