Glycosylidene carbenes -: Part 26 -: The intramolecular F•••HO hydrogen bond of 1,3-diaxial 3-fluorocyclohexanols

According to ab-initio calculations, the CF...HO H-bond in 1,3-diaxial 3-fluorocyclohexanol is characterized by d(F...H)= 2.08 Angstrom, d(F,O) = 1.88 Angstrom, and angle (F...H-O) = 138 degrees, and by Delta E between 1.2 and 4.1 kcal/mol, depending upon the reference system. Relative to the OH stretching frequency of axial cyclohexanol, the OH stretching frequency of 1,3-diaxial 3-fluorocyclohexanol is shifted by Delta omega = 7 cm(-1). The rigid fluoro diols D-4 and L-4 were prepared from tetrahydroxy-p-benzoquinone in 11 steps and 1% overall yield. The IR spectrum of 4 in CCl4 soln. is characterized by Delta nu = 7 cm(-1) for the axial and Delta nu = 44 cm(-1) for the equatorial OH group. A relatively strong intramolecular CF...HO bond of 4 in CCl4 is evidenced by the large through-space coupling (5)J(F,HO) of 9.3 Hz. Nevertheless, this F...HO bond is disrupted in ethereal solvents, while the bifurcated O...HO bond subsists. In CCl4, the carbene generated from the glucosylidene-derived diazirine 5 reacted more rapidly with the axial OH group of D-4 and L-4 than with the equatorial one. This regioselectivity is in keeping with the weaker H-bond of the axial OH group. The regioselectivity is lower in ethers, but its solvent dependence does not parallel solvent basicity. This is nor satisfactorily explained by the differential interaction of the ether solvents with the axial and equatorial OH groups, as evidenced by the solvent dependence of their chemical shift, but must also reflect the different interaction of the solvents with the carbene derived from 5, leading to ylides. The lower solvent dependence of the anomeric selectivity for the glycosidation of the equatorial OH group is a consequence of the coordination of the intermediate oxycarbenium ion with O-C(1) and O-C(3) rather than with the solvent. Under conditions of competitive glycosylation in CCl4, the fluoro alcohol D-22 reacted more slowly than the alcohol L-24, evidencing the intramolecular F...HO H-bond.