INTRAMOLECULAR PI-STACKING AND ASYMMETRIC INDUCTION - A SEMIEMPIRICAL THEORETICAL-STUDY

The conformations of several substituted cyclohexyl esters involved in highly diastereoselective organic reactions that have been rationalized by intramolecular a-stacking were investigated by resorting to the semiempirical SIBFA procedure. Different cases, for which experimental results featuring a large set of chiral auxiliaries are available, were studied. For the cyclohexyl-based asymmetric crotonates and glyoxylates, the stabilization of the sterically demanding face-to-face ''stacked'' conformers increases, as expected, with the absolute value of the dispersion energy contribution. We report a good correlation between the experimental de and the stability of the stacked conformer over the other possible ones. In addition, the analysis of the energy contributions for these two series of esters also indicates that the electrostatic forces are of prime importance for the conformational preferences observed. For both sets of compounds, this last result suggests substitution patterns that could be used to improve the auxiliaries' efficiency. Proton NMR shieldings calculated for the most stable conformations are in good agreement with available experimental data and therefore support our energetics results. For butadienyl O-methylmandelate, the phenyl ring is found to be roughly perpendicular to the conjugated diene moiety, a feature in qualitative agreement with that of another recently published semiempirical study on the same compound. The quality of the correlation between the stacked conformers population and the reported diastereoselectivities. shows the importance of the conformations of the chiral substrate for the stereochemical outcome of the read-ions considered in this study.