Glycosylation Of 2-Nitroglycals Activated By Dithiocarbamate Salt

Abstract

2-nitroglycals are important precusors for the synthesis of many amino deoxy sugars, which are ubiquitous in several biologically active molecules such as glycoproteins or oligosaccharides. 2-Nitroglycals are also valuable synthetic intermediates as they readily undergo Michael addition. There are four possible Michael addducts from this reaction as it generates two new stereogenic carbons on the pyranoside. Both, an α- and β-glycoside can be generated from the addition of a nucleophile at the anomeric position. Herein, we report a novel method for stereoselective Michael addition of 2-nitroglycals without using strong base or acid as catalysts. Firstly, 2-nitroglycals were synthesized from glycals by a modified nitration method using combination of silver nitrate and propionyl chloride resulted in 27–44% yield. Nitration on glycals by acetic anhydride and nitric acid followed by elimination afforded the desired 2-nitroglycals in 45% yield over 2 steps. Next, Michael additions of 2-nitroglycals were demonstrated with S-, N-, and O-nucleophiles using sodium diethyldithiocarbamate (NaDTC; Na+-SC(S)NEt2) as an activator. Activation of 2-nitroglycals by NaDTC proceeded smoothly with various S-nucleophiles and resulted in thioglycosides in high yield and selectivities. The thioglycosides are valuable intermediates for complex carbohydrate synthesis. The use of sodium diethyldithiocarbamate as the activator allows the glycosylation to be performed under mild and non-anhydrous conditions which is more convenient than previously described anhydrous procedures. Interestingly, α-thioglycosides were obtained in 61–98 % yield when highly nucleophilic aliphatic thiols were used. On the other hand, β-thioglycosides were formed in 75–93 % yield when heterocyclic or aromatic thiols were used. The stereochemisrty of the thioglycosides were identified by NMR spectroscopy and confirmed by X-ray crystallography.