Dehydrative Glycosylation with Activated Diphenyl Sulfonium Reagents. Scope, Mode of C(1)-Hemiacetal Activation, and Detection of Reactive Glycosyl Intermediates

The development of a method for direct dehydrative glycosylations with 1-hydroxyglycosyl donors employing the reagent combination of triflic anhydride and diphenyl sulfoxide is described. The one-pot coupling method is a facile process which is applicable to a variety of carbohydrate coupling partners. Oxygen-18-labeling studies are consistent with the first step in carbohydrate activation being the formation of an anomeric oxosulfonium intermediate. This reactive glycosyl species ( 35 ) is observable in low-temperature NMR experiments when 2,3,4,6-tetra- O -methyl- d -mannopyranose is activated as the glycosyl donor. When the dehydrative glycosylation reaction is performed in the presence of the triflic acid scavenger 2-chloropyridine, NMR analysis reveals that the glycosyl oxosulfonium intermediate 35 is converted to the corresponding anomeric 2-chloropyridinium species 36 .