4JCOCCH and 4JCCCCH as probes of exocyclic hydroxymethyl group conformation in saccharides

1H NMR spectra of aldohexopyranosyl rings containing 13C-enrichment at either C1 or C3 reveal the presence of long-range 4JC1,H6R/S and 4JC3,H6R/S whose magnitudes depend mainly on the O5−C5−C6−O6 torsion angle. Using theoretical calculations (density functional theory, DFT; B3LYP/6-31G*) and conformationally constrained experimental model compounds, the magnitudes and signs of 4JC1,H6R/S and 4JC3,H6R/S have been established, and their dependencies on the geometry of the C1−O5−C5−C6−H6R/S and C3−C4−C5−C6−H6R/S coupling pathways, respectively, were determined. The latter dependencies mimic that observed previously for 4JHH in aliphatic compounds such as propane. DFT calculations also showed that inclusion of non-Fermi contact terms is important for accurate predictions of 4JCH values. Application to methyl α- and β-d-glucopyranosides reveals different rotameric distributions about their hydroxymethyl groups, with the β-anomer enriched in the gt rotamer, in agreement with recent multi-J redundant coupling analyses. 4JC1,H6R/S and 4JC3,H6R/S are expected to complement other recently developed J-couplings for the assignment of hydroxymethyl group conformation in oligosaccharides containing 1,6-glycosidic linkages.