<i>De Novo</i> Enantioselective Synthesis of Hexafluorinated <scp>d</scp>-Glucose

We report a <i>de novo</i> enantioselective synthesis of 2,3,4-trideoxy-2,2,3,3,4,4-hexafluoro-d-<i>glycero</i>-hexopyranose (hexafluorinated d-glucose), an iconic polar hydrophobic glycomimetic. The 12-step synthesis features robust and reproducible chemistry and was achieved by incorporating an asymmetric dihydroxylation step to install the stereogenic center with excellent enantioselectivity (95:5 <i>er</i>). Virtual enantiopurity (>99.5% <i>ee</i>) was further reached using a simple crystallization procedure and the absolute confirmation was ascertained by X-ray analysis. The synthetic route also allowed access to the novel hexafluorinated heptose derivative 2,3,4-trideoxy-2,2,3,3,4,4-hexafluoro-l-<i>threo</i>-heptopyranose.