CONFORMATIONAL STUDIES BY DYNAMIC NMR .47. CONFORMATION, STEREODYNAMICS, AND CHIRAL SEPARATION OF THE ROTATIONAL ENANTIOMERS OF HINDERED NAPHTHYL KETONES

A number of alpha-naphthyl ketones bearing a methyl group in the 2-position of the naphthalene ring adopt a twisted conformation, yielding a pair of rotational enantiomers owing to the restricted rotation about the naphthalene-carbonyl bond. NOE measurements indicate that the twisted conformation is almost exactly orthogonal. The enantiomerization barriers were determined by variable-temperature dynamic NMR spectroscopy, with monitoring of either the anisochronous signals of prochiral substituents or the pairs of signals of the enantiomers themselves, made detectable at low temperature by the addition of a chiral auxiliary agent. The free energies of activation cover a range of 8-20 kcal mol-1, depending on the steric hindrance of the various acyl groups. Molecular mechanics calculations suggest that enantiomerization occurs through a pathway where the carbonyl function passes position 2, rather than position 8, of the naphthalene ring. In the case of a 1,5-disubstituted acyl derivative containing the tert-butyl moiety (7), the expected meso and racemic conformers were both observed in solution, whereas only the meso structure was present in the crystals (obtained by the usual slow crystallization procedure) as judged by CP MAS solid-state NMR spectra and by low-temperature solution spectra in nonequilibrium conditions. Low-temperature (-15-degrees-C) chiral high-performance liquid chromatography (LT-ChirHPLC) was employed to separate and identify the two enantiomers of 6 as well as the three conformers (meso, SS, and PR) of 7. The low-temperature CD spectra of the rotational enantiomers of 6 and 7 were obtained and the absolute configurations assigned by connecting on-line a CD spectrometer to the LT-ChirHPLC apparatus. Respectively, the S and SS configurations were found to correspond to the conformational enantiomers with the shorter retention times ((R,R)-DAC-DNB column).