Computational reexamination of the eclipsed conformation in cis-2-tert-butyl-5-(tert-butylsulfonyl)-1,3-dioxane

The conformational free energy differences, ΔG° values, for the methyl sulfide, methyl sulfoxide, methyl sulfone, tert-butyl sulfide, tert-butyl sulfoxide, and tert-butyl sulfone groups at C(5) in the 1,3-dioxane ring have been calculated at two different levels, B3LYP/6-31G(d) and B3LYP/6-311++G(d,p). There is good agreement between experimental and calculated values, particularly in the case of data obtained at the lower level of theory, B3LYP/6-31G(d). In order to get information that could help understand the nature of the effects present in the molecules of interest, the charge distribution in representative compounds was analyzed by means of the natural bond orbital (NBO) analysis. NBO calculations indicate the existence of substantial negative charges at oxygen and significant positive charge at sulfur. This observation seems to support the argument the existence of electrostatic, attractive interactions between the endocyclic oxygens and the axial sulfonyl group. From the second order perturbation theory analysis of Fock matrix, two σC–C → σ*S–O delocalizing interactions are observed in the methyl-inside conformer of cis-2-tert-butyl-5-(methylsulfonyl)-1,3-dioxane derivative cis-7. These results are in line with anti-periplanar σC–C → σ*S–O hyperconjugative interactions that help stabilize the methyl-inside conformation of cis-7, as previously found by 1H NMR analysis. By contrast, NBO analysis does not provide evidence for the existence of σC–C → σ*S–O hyperconjugative interactions that might help stabilize the eclipsed tert-butyl—outside conformation previously found in the solid-state crystallographic structure of analog cis-1. Because of the threshold value of the NBO calculations, if present such syn-periplanar stereoelectronic interaction should be less than 0.5 kcal mol−1. This observation suggests that an anti-periplanar orientation of the interacting orbitals is more effective relatively to the corresponding syn-periplanar orientation.