Regioselective functionalizations and conformational studies of di-O-isopropylidene-myo-inositol derivatives

(±)-1,2:4,5-Di-O-isopropylidene-myo-inositol (5) and (±)-1,2:5,6-di-O-isopropylidene-myo-inositol (6) could be regioselectively functionalized in reactions including alkylation, acylation, and silylation at HO-3 in preference to HO-6 and HO-4, respectively, under specific conditions. The presence of intramolecular hydrogen bonding was evident in IR and 1H NMR spectra, and the HO-3 group was identified as the hydrogen-bonding donor in 5 and 6. In their crystalline states, diol 5 prefers a chair conformation and diol 6 a twist boat (skew) conformation. Both compounds appear to have substantial populations of chair conformations in the gas and solution phases, on the basis of the MM-2 energy minimizations and comparisons of vicinal coupling constants observed in the 1H NMR spectra (in CDCl3 and Me2SO-d6) and calculated from the crystal and MM-2 conformations. It is suggested as an explanation for the observed selectives that the kinetic acidity of the HO-3 group may be enhanced through its intramolecular hydrogen bonding with the cis-vicinal oxygen, or the nucleophilicity of the 3-alkoxide may be enhanced due to its interaction with the cis-vicinal oxygen in a manner similar to the through-space α-effect.