Glycosylidene Carbenes. Part 23. Regioselective glycosidation of deoxy‐ and fluorodeoxy‐myo‐inositol derivatives

Abstract

AbstractTo 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 (Scheme 1) 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 (Scheme 2) 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 (Fig. 2). 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 (Scheme 3) 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 (Scheme 4) 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 (Scheme 4). The regio‐ and diastereoselectivities of the glycosidation correlate with the H‐bonds in the starting diols.