The conformation of tetrafluorinated methyl galactoside anomers: crystallographic and NMR studies

The first single-crystal X-ray diffraction study of tetrafluorinated monosaccharide derivatives is presented. Both alpha- and beta-methyl 2,3-dideoxy-2,2,3,3-tetrafluoro-D-galactopyranoside anomers adopt the C-4(1) conformation. The values for the C1-O1 and C1-O5 bond lengths and the O5-C1-O1-CH3 dihedral angles are in line with what can be expected from the anomeric and exo-anomeric effects. The chair conformations are slightly distorted, presumably due to repulsion between 1,3-diaxial C-O and C-F bonds. The asymmetric unit of both compounds contains up to three independent molecules, which differ in the conformation of the hydroxymethyl group (including in one case a 'forbidden' gg rotamer). The molecular packing of the beta-anomer shows a clear segregation between fluorinated and hydrophilic domains, while for the alpha-anomer the regions of fluorine segregation are broken by interleafing of OMe groups. There is one close OH center dot center dot center dot F contact, which is likely to arise from the crystal packing. NMR studies show that the two anomers also adopt a C-4(1) conformation in solution (D2O, CDCl3). (C) 2011 Elsevier Ltd. All rights reserved.