D-Glucosamine, and derivatives thereof, are found in many biologically important saccharides, including glycosaminoglycans (GAGs), and in various classes of oligosaccharides. Glucosamines can also serve as useful chirons. Consequently, synthetic derivatizations that may have diverse applications are of value, and the con-version of the 2-amino group into a 2-azido group is a widely useful transformation. The 2-azido group both acts as a latent amine, latterly re-accessible by several reductive chemistries, and plays an important role in α-selective glycosylations. For some years, the method of choice for the amine to azide conversion was the use of freshly prepared triflic azide, but more recently the use of imidazole sulfonyl azide salts has been demonstrated as an effective and scalable alternative. This article takes into account the original safety concerns regarding the synthesis and handling/storage of these azide transfer reagents, and provides a reliable and scalable procedure for preparation of 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-α,β-d-glucopyranose. It has been already employed as a highly valuable intermediate towards synthesis of heparin-like GAGs, and is also a core intermediate relevant to the wider synthesis of other GlcN-containing targets.
