Fluorinated analogues of amicetose and rhodinose - novel racemic and asymmetric routes

Trifluoroethanol was converted into difluorinated (racemic) analogues of amicetose and rhodinose by metallated difluoroenol acetal chemistry, protection, release of the latent difluoromethyl ketone, stereoselective reduction and ozonolysis in acidic methanol. A fortuitous separation of diastereoisomers allowed the diastereoisomeric pyranoses to be obtained cleanly. Though reductive defluorination allowed a facile entry to the route, the corresponding monofluoro sugar analogues could not be separated. Instead, Sharpless asymmetric epoxidation followed by epoxide ring-opening with an unusual nucleophilic fluoride source allowed enantiomerically highly enriched and selectively protected fluorodiols to be obtained. Ozonolysis then afforded the methyl pyranosides, which could be transformed in a number of ways.