Conformational analysis of 2-(1-adamantyl)-3-hydroxybutyric acid by 1H NMR spectroscopy and computational studies

Erythro- and threo-isomers of 2-(1-adamantyl)-3-hydroxybutyric acid (1) have been synthesized, separated and characterized by 1H NMR spectroscopy. The NMR study showed that threo-1 is present predominantly in intramolecular H-bonded form, whereas there is a rotational mobility in erythro-1. The conformations of erythro- and threo-isomers were examined computationally using the AMBER force field and density functional calculations. The computed results were found to be in agreement with the observed experimental results, that is threo-1 was found to be intramolecularly hydrogen bonded, while the most stable conformation for erythro-1 was non-hydrogen bonded. The large difference between the values of the vicinal coupling constant in 1H NMR obtained in CDCl3, CD3CN and d6-DMSO can be an indicator for the intramolecular H-bonding in the cases when X-ray structural analysis and high-level computations are not possible.