Spectroscopic and molecular mechanics calculations of discrimination between enantiomers possessing an electron rich aromatic group directly attached to the chiral carbon atom with optically pure benzoyl derivatives

Abstract

The discrimination between enantiomers that have a chiral centre directly attached to the electron rich aromatic ring by interactions with optically pure electron deficient aromatic compounds was studied by ¹H NMR and molecular mechanics calculations. The enantiomeric spectroscopic discrimination is due to formation of non-bonding interactions which lead to the formation of diastereoisomeric complexes. The calculated HOMO energy values for electron rich racemic compounds and LUMO values for electron poor resolving agents are in good agreement with the observed chemical shift differences between enantiomers by ¹H NMR. Exceptions to these observations are seen for compounds which possess groups that are in a position to sterically push apart the complexation components and thus decrease the binding energy and diminish the enantiomeric discrimination. The discrimination strongly depends on concentration of the components in the solution, their ratio, temperature and the polarity of the media. Polar racemic compounds show the smallest enantiomeric discrimination by increasing the polarity of the media. For good enantiomeric discrimination both chiral centres must be rigidly bound to the aromatic rings. If the chiral centre is separated from the aromatic ring by flexible bonds the enantiomeric recognition fails despite the formation of strong non-bonding interactions. The binding energies calculated by AMBER and MM+ force fields are relatively weak (∼2 kcal mol^–1) suggesting that only a small portion of the molecules in solution are incorporated into the complexes. Our attempt to provide evidence for selective binding of only one enantiomer to the template molecule was unsuccessful. Nevertheless our results support the formation of inter-exchangeable diastereoisomeric complexes. Although it might be argued that two sets of signals should also be obtained for the template molecule, all our ¹H NMR spectra show only one set of signals for the optically pure template and two sets of signals for the racemic component in their chloroform solutions. Despite low binding energies enantiomeric discrimination with strong electron accepting resolving agents can be achieved in as low as 0.01 mol dm^–3 chloroform solution.