Synthesis of 1,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-α,β-d-glucopyranose Using the Diazo-Transfer Reagent Imidazole-1-sulfonyl Azide Hydrogen Sulfate

d-Glucosamine, and derivatives thereof, are found in many biologically important saccharides, ^1,2 including glycosaminoglycans (GAGs), and in various classes of oligosaccharides. Glucosamines can also serve as useful chirons. ³ Consequently, synthetic derivatizations that may have diverse applications are of value, and the conversion 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, ⁴ and plays an important role in α-selective glycosylations. ⁵ For some years, the method of choice for the amine to azide conversion was the use of freshly prepared triflic azide, ⁶ but more recently the use of imidazole sulfonyl azide salts has been demonstrated as an effective and scalable alternative. ⁷ This article takes into account the original safety concerns regarding the synthesis and handling/storage of these azide transfer reagents, ⁸ 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, ⁹ and is also a core intermediate relevant to the wider synthesis of other GlcN-containing targets.