# Optimization of Azidophenylselenylation of Glycals for the Efficient Synthesis of Phenyl 2-Azido-2-Deoxy-1-Selenoglycosides: Solvent Control

## TL;DR

This paper improves a chemical method to efficiently create specific sugar derivatives using optimized solvents.

## Contribution

The study identifies optimal solvents for synthesizing phenylseleno glycosides from different glycal configurations.

## Key findings

- Galacto-configured glycals require nitrile solvents for efficient azide-ion transfer.
- Gluco-configured glycals need non-polar solvents like benzene for complete conversion.
- The optimized method successfully synthesizes derivatives of multiple sugar types.

## Abstract

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.