Towards conformationally-locked difluorosugar analogues : an unexpected sense of dihydroxylation

Difluorinated cyclooctenones, synthesised using RCM, can be used as templates for stereoselective oxidative transformations to products that undergo transannular reactions to afford conformationally-locked analogues of 2-deoxy-2,2-difluorosugars with different stereochemical relationships between the C-2 and C-3 hydroxyl groups

Towards novel difluorinated sugar mimetrics; syntheses and conformational analyses of highly-functionalised difluorinated cyclooctenones

Highly-functionalised difluorinated cyclooctenones were synthesised from trifluoroethanol using either metallated difluoroenol acetal or carbamate chemistry, followed by a [2,3]-Wittig rearrangement or aldol reaction. Efficient RCM reactions afforded the title compounds which showed rather restricted fluxional behaviour by VT 19F NMR. Topological characterisation by molecular modelling and NOESY/ROESY experiments offered a number of challenges, but allowed the identification of two favoured boat-chair conformers which interconverted by pseudorotation with relatively large activation barriers

Synthesis of bicyclic difluorinated analogues of sugars

This thesis describes the synthesis of gem-difluorinated cyclooctenone analogues using building block approaches based on the RCM with Grubbs' catalysts.;Des- and gem-dialkyl-substituted difluorodienes were synthesised from commercially available trifluoroethanol by dehydrofluorination/metalation, trapping, allylation and [2,3]-Wittig rearrangement successfully.;The gem-difluorinated dienes produced the corresponding difluorinated cyclooctenones smoothly and in good yields. However, a dithioketal-containing diene did not afford any cyclic product. Thorpe-lngold effect was also observed from the concentration study of des- and gem-dimethyl dienes in the RCM reaction. The gem-dimethyl diene cyclised faster than des-dimethyl diene, and the des-dimethyl diene could cyclise only at low concentration (0.001 M).;The cyclooctenone analogues have interesting topological conformations, which were studied by NMR experiments and computational calculations.;The dihydroxylation and stero-controlled epoxidation were developed on unique 8- membered ring molecules. Dihydroxylation reactions gave mixtures of diastereomeric triol products, which underwent transannular collapse to afford bicyclic products. The stereo-controlled epoxidation with methyl(trifluoromethyl) dioxirane gave the corresponding trans-epoxyalcohol in good yields. The epoxides were very stable under acid conditions however, in basic aqueous solution with microwave irradiation, they afforded bicyclic molecules by a transannular reaction via hemiaminal formation next to fluorine atoms. The newly synthesised conformationally locked difluorinated bicyclic molecules are hydrolytically resistant sugar mimics