Optimization of Azidophenylselenylation of Glycals for the Efficient Synthesis of Phenyl...

Azidophenylselenylation (APS) of glycals is a straightforward transformation for preparing phenylseleno 2-azido-2-deoxy derivatives, which are useful blocks in the synthesis of 2-amino-2-deoxy-glycoside-containing oligosaccharides. However, the previously developed APS methods employing the CH₂Cl₂ as solvent, Ph₂Se₂-PhI(OAc)₂ (commonly known as BAIB), and a source of N₃^- are still not universal and show limited efficiency for glycals with gluco- and galacto-configurations. To address this limitation, we revisited both heterogeneous (using NaN₃) and homogeneous (using TMSN₃) APS approaches and optimized the reaction conditions. We found that glycal substrates with galacto- and gluco-configurations require distinct conditions. Galacto-substrates react relatively rapidly, and their conversion depends mainly on efficient azide-ion transfer into the organic phase, which is promoted by nitrile solvents (CH₃CN, EtCN). In contrast, for the slower gluco-configured substrates, complete conversion requires a non-polar solvent still capable of azide-ion transfer, such as benzene. These observations were applied to the optimized synthesis of phenylseleno 2-azido-2-deoxy derivatives of d-galactose, d-glucose, l-fucose, l-quinovose, and l-rhamnose.