ACYLKETENE [4+2] CYCLOADDITIONS - DIVERGENT DENOVO SYNTHESIS OF 2,6-DIDEOXY SUGARS

The synthetic methodology demonstrated herein provides a divergent, de novo synthetic pathway to 2,6-dideoxy carbohydrates. Pyranone 2, which was prepared by [4 + 2] cycloaddition of the acylketene generated from dioxinone 1 with butyl vinyl ether, was converted in a straightforward manner to arabino-hexopyranosides olivoside 11 and oleandroside 12, and branched sugars olivomycoside 14 and chromoside B 15, with near complete control of relative stereochemistry at the three newly introduced stereogenic centers. Olivoside 11 proved to be a pivotal intermediate for elaboration to the ribo, lyxo, and xylo families of 2,6-dideoxy carbohydrates. Selective Mitsunobu inversion at C3 of 11 provided ready access to the ribo-pyranoside digitoxoside 17, whereas selective inversion at C4 of 11 or 12 via the intermediacy of the O4-trifluoromethanesulfonate ester gave rise to the lyxo-pyranosides olioside 23 and diginoside 21, respectively. A high-yielding sequence of reactions for the elaboration of 11 to lyxo-anhydro sugar 25 furnished an intermediate for the direct conversion to the xylo-pyranosides boivinoside 30 and sarmentoside 31 by a regioselective epoxide opening.