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

Developing an asymmetric, stereo-divergent route to selected 6-deoxy-6-fluoro-hexoses

Free radical bromination and nucleophilic fluorination allows the conversion of Me sorbate into the 6-fluoro analog which undergoes sequential asym. dihydroxylation reactions. A range of 6-deoxy-6-fluoro-sugars were prepd. by using different combinations of ligands. While the enantiomeric excesses obtained were comparable to those from other 6-substituted sorbates, the regioselectivity of dihydroxylation was moderate, with both 2,3- and 4,5-diols being obtained. A successful temporary persilylation strategy was evolved to convert the products of dihydroxylation rapidly to the fluoro-sugars 6-deoxy-6-fluoro-L-idose, 6-fluoro-L-fucose and 6-deoxy-6-fluoro-D-galactose, which were obtained in overall yields of 4%, 6% and 8% from Me 6-fluoro-hexa-2E,4E-dienoate