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Synthesis of bicyclic difluorinated analogues of sugars

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posted on 15.12.2014, 10:35 by Emi Uneyama
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.


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University of Leicester

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