C2-amidoglycosylation with glycal donors for the synthesis of 2-N-acylamino-2-deoxypyranosides. Development, scope, and mechanism

A one-pot C2-amidoglycosylation reaction for the synthesis of 2-N-acylamino-2-deoxypyranosides from glycal donors has been developed. In the reaction, activation of glycal donor by a sulfoxide and triflic anhydride followed by regio- and stereoselective transfer of an amide nucleophile generates an oxazoline intermediate, which can glycosylate a wide variety of nucleophiles in situ to provide the corresponding C2-amidoglycosides. C2-Acetamidoglycosylation with glucals using N-(TMS)acetamide for the first time affords the naturally occuring 2-N-acetylamino-2-deoxypyranoses in a one-pot procedure. The diastereoselectivity of the C2-amidoglycosylation reaction can be controlled by the choice of sulfoxide reagent, and C2-amidosugars derived from glucose, mannose, and galactose can all be synthesized. Tracking of the reaction by low temperature NMR spectroscopy employing isotope-labeled substrates suggests a mechanism involving the formation of a C2-sulfonium glycosyl imidate as the key intermediate in the nitrogen transfer process.