Phenanthroline-Catalyzed Stereoselective Formation of α-1,2-cis 2-Deoxy-2-Fluoro Glycosides.

Phenanthroline is a heterocyclic aromatic organic compound and commonly used in coordination chemistry acting as a bidentate ligand. The C4 and C7 positions of phenanthroline can often be substituted to change the binding capabilities of the ligand. Recently, there has been a push in the field of chemistry to create environmental-friendly chemical methodologies by utilizing catalysts and minimizing solvent. Herein, we have illustrated how, at high concentrations with minimal use of solvent, the C4 and C7 positions of phenanthroline can be tuned to develop an efficient and stereoselective catalyst for the formation of α-1,2-cis-fluorinated glycosides. By activating 2-deoxy-2-fluoro glycosyl halides with phenanthroline-based catalysts, we have been able to achieve glycosylations with high levels of α-selectivities and moderate to high yields. The catalytic system has been applied to several glycosyl halide electrophiles with a range of glycosyl nucleophilic acceptors. The proposed mechanism for this catalytic glycosylation system has been investigated by density functional theory calculations, indicating that the double SN2 displacement pathways with phenanthroline catalysts have lower barriers and ensure stereoselective formation of α-1,2-cis-2-fluoro glycosides.

Phenanthroline-Catalyzed Stereoretentive Glycosylations.

Carbohydrates are essential moieties of many bioactive molecules in nature. However, efforts to elucidate their modes of action are often impeded by limitations in synthetic access to well-defined oligosaccharides. Most of the current methods rely on the design of specialized coupling partners to control selectivity during the formation of glycosidic bonds. Reported herein is the use of a commercially available phenanthroline to catalyze stereoretentive glycosylation with glycosyl bromides. The method provides efficient access to α-1,2-cis glycosides. This protocol has been performed for the large-scale synthesis of an octasaccharide adjuvant. Density-functional theory calculations, together with kinetic studies, suggest that the reaction proceeds by a double SN 2 mechanism.