Glycosylidene carbenes. Part 23. Regioselective glycosidation of deoxy- and fluorodeoxy-myo-inositol derivatives

Article abstract of DOI:10.1002/hlca.19960790424

To demonstrate the relevance of the kinetic acidity of individual OH groups for the regioselectivity of glycosylation by glycosylidene carbenes, we compared the glycosylation by 1 of the known triol 2 with the glycosylation of the diol D-3 and the fluorodiol L-4. Deoxygenation with Bu₃SnH of the phenoxythiocarbonyl derivative of 5 or the carbonothioate 6 gave the racemic alcohol (±)-7. The enantiomers were separated via the allophanates 9a and 9b, and desilylated to the deoxydiols D- and L-3, respectively. The assignment of their absolute configuration is based upon the CD spectra of the bis(4-bromobenzoates) D- and L-10. The (+)-(R)-1-phenylethylcarbamates 13a and 13b were prepared from the fluoroinositol (±)-11 via (±)-4 and the silyl ether (±)-12 and separated by chromatography. The absolute configuration of 13a was established by X-ray analysis. Decarbamoylation of 13a (→ L-12) and desilylation afforded the fluorodiol L-4. The H-bonds of D-3 and L-4 in chlorinated solvents and in dioxane were studied by IR and ¹H-NMR spectroscopy. In both diols, HO-C(2) forms an intramolecular, bifurcated H-bond. There is an intramolecular H-bond between HO-C(6) and F in solutions of L-4 in CH₂Cl₂, but not in 1,4-dioxane; the solubility of L-4 in CH₂Cl₂ is too low to permit a meaningful glycosidation in this solvent. Glycosidation of D-3 in dioxane by the carbene derived from 1 followed by acetylation gave predominantly the pseudodisaccharides 18/19 (38%), derived from glycosidation of the axial OH group besides the pseudodisaccharides 16/17 (13%) and the epoxides 20/21 (7%), derived from protonation of the carbene by the equatorial OH group. Similarly, the reaction of L-4 with 1 led to the pseudodisaccharides 28/29 (46%) and 26/27 (14%), derived from deprotonation of the axial and equatorial OH groups, respectively. Formation of the epoxides involved deprotonation of the intramolecularly H-bonded tautomer, followed by intramolecular alkylation, elimination, and substitution. The regio- and diastereoselectivities of the glycosidation correlate with the H-bonds in the starting diols.