Efficient Synthesis of Azido Sugars using Fluorosulfuryl Azide Diazotransfer Reagent

Abstract

Azide-containing sugars are important tools for the synthesis of biologically relevant 1,2-cis-glycosides and for bioconjugation chemistry. Previous strategies for the installation of a non-participating C2-azido functionality use harsh conditions and long reaction times. Herein, we report the synthesis of azido sugars using fluorosulfuryl azide (FSO2N3; 1) with a Cu(II) catalyst as a safe and efficient diazotransfer reagent. Common hexosamine substrates were converted to 2-azido-2-deoxy sugars in less than 5 minutes in quantitative yield. Glycosyl donors with orthogonal protecting groups were readily prepared from these azido sugars with good overall yield and a single column purification. The diazotransfer protocol was also efficiently used on other amino sugar derivatives, including aminoglycosides and substrates with amine-containing linkers. This optimized method will expand access to important non-participating C2-azido protecting groups and other azido sugar derivatives.