Absolute configuration of natural cyclohexene oxides by time dependent density functional theory calculation of the optical rotation: the absolute configuration of (-)-sphaeropsidone and (-)-episphaeropsidone revised.

The optical rotatory power of some natural cyclohexene oxides, such as (+)-chaloxone, 1, (+)-epiepoformine, 2, (+)-epoformine, 3, (+)-epoxidone, 5, (-)-sphaeropsidone, 6, (-)-episphaeropsidone, 7, and the synthetic compound (+)-epitheobroxide, 4, has been calculated by means of the TDDFT/B3LYP method using the 6-31G(d) and aug-cc-pVDZ basis sets, both in the gas phase and in solution by means of the polarizable continuum model. For compounds 1 and 2, which possess high (about 300 units) optical rotations, gas-phase calculations with the smaller basis set are able to reproduce the experimental values both in sign and order of magnitude. By contrast, a larger basis set is required to satisfactorily simulate the OR values of 3 and 4, which show smaller (about 100 units or less) rotations. The inclusion of the solvent effects is different for different compounds; for 1 and 2, it leads to a better agreement between experiment and prediction, while for 3 and 4, the presence of hydrogen bonding groups makes the application of continuum solvation models less satisfactory. For the flexible system 5, the absolute configuration could not be determined using gas-phase calculations and the smaller basis set, but both inclusion of solvent and larger basis set effects are compulsory. It is noteworthy that calculations both in the gas phase and in the solvent lead to a positive rotatory power for the laevorotatory natural compounds 6 and 7 if the ACs reported in the literature are employed to do the theoretical prediction. This strongly indicates that the ACs previously assigned to these compounds in the literature are not correct and that the TDDFT prediction of OR values has become by now a practicable tool for AC assignments.