A new 6-C-alkylation from an alkyl mannofuranoside 5,6-cyclic sulfate

Methyl 6-C-alkyl-6-deoxy-α-d-mannofuranoside derivatives have been synthesized from methyl 2,3-O-isopropylidene-5,6-O-sulfuryl-α-d-mannofuranoside (1). In a Path A, reaction of the 5,6-cyclic sulfate 1 with 2-lithio-1,3-dithiane afforded 2-(methyl 6-deoxy-2,3-O-isopropylidene-α-d-mannofuranosid-6-yl)-1,3-dithiane (2). Treatment of 2 with n-butyllithium then alkyl iodide gave the corresponding 2-(methyl 5-O-alkyl-6-deoxy-2,3-O-isopropylidene-α-d-mannofuranosid-6-yl)-1,3-dithiane. Reaction of 2 with n-butyllithium and 5,6-cyclic sulfate 1 furnished 2-[methyl 6-deoxy-2,3-O-isopropylidene-5-O-(methyl 6-deoxy-2,3-O-isopropylidene-α-d-manno-furanosid-6-yl)-α-d-mannofuranosid-6-yl]-1,3-dithiane. 2-(Methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-α-d-mannofuranosid-6-yl)-1,3-dithiane was converted into the lithiated anion, which after treatment with alkyl halide afforded the corresponding 2-alkyl-C-(methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-α-d-mannofuranosid-6-yl)-1,3-dithiane. In a Path B, 5,6-cyclic sulfate 1 reacted with 2-alkyl-2-lithio-1,3-dithiane derivatives, which led after acidic hydrolysis to 2-alkyl-2-(methyl 6-deoxy-2,3-O-isopropylidene-α-d-mannofuranosid-6-yl)-1,3-dithiane accompanied by methyl 6-deoxy-2,3-O-isopropylidene-α-d-lyxo-hexofuranos-5-uloside as the by-product. This methodology was applied to synthesize 2-(methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-α-d-mannofuranosid-6-yl)-2-(methyl 6-deoxy-2,3-O-isopropylidene-α-d-mannofuranosid-6-yl)-1,3-dithiane.