GLYCOSYLIDENE CARBENES - PART 26 - THE INTRAMOLECULAR F-CENTER-DOT-CENTER-DOT-CENTER-DOT-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. Re lative to the OH stretching frequency of axial cyclohexanol, the OH st retching frequency of 1,3-diaxial 3-fluorocyclohexanol is shifted by D elta omega = 7 cm(-1). The rigid fluoro diols D-4 and L-4 were prepare d from tetrahydroxy-p-benzoquinone in 11 steps and 1% overall yield. T he 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 evid enced by the large through-space coupling (5)J(F,HO) of 9.3 Hz. Nevert heless, this F...HO bond is disrupted in ethereal solvents, while the bifurcated O...HO bond subsists. In CCl4, the carbene generated from t he glucosylidene-derived diazirine 5 reacted more rapidly with the axi al OH group of D-4 and L-4 than with the equatorial one. This regiosel ectivity is in keeping with the weaker H-bond of the axial OH group. T he regioselectivity is lower in ethers, but its solvent dependence doe s not parallel solvent basicity. This is nor satisfactorily explained by the differential interaction of the ether solvents with the axial a nd equatorial OH groups, as evidenced by the solvent dependence of the ir chemical shift, but must also reflect the different interaction of the solvents with the carbene derived from 5, leading to ylides. The l ower solvent dependence of the anomeric selectivity for the glycosidat ion 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 CCl 4, the fluoro alcohol D-22 reacted more slowly than the alcohol L-24, evidencing the intramolecular F...HO H-bond.