Abstract
Enantiomeric excess (ee) is a measure of the purity of an enantiomer of a chiral compound with respect to the presence of the complementary enantiomer. It is an important aspect of chemistry, especially in the fields of pharmaceuticals and asymmetric catalysis.
Existing methods for determination of enantiomeric excesses using nuclear magnetic resonance (NMR) spectroscopy mostly rely on special chiral reagents (auxiliaries) that form two or more diastereomeric complexes with a chiral compound. As a result of this, the NMR spectrum of each enantiomer is different, allowing the determination of enantiomeric excess.
In this Account, we describe a molecular design process that has allowed us to prepare pro chiral solvating agents for NMR determination of ee of a wide variety of analyte types. At the outset of this work, we initially encountered the phenomenon of NMR peak splitting in the oxoporphyrinogen (OxP) host component of a supramolecular host guest complex, where the extent of the splitting is apparently proportional to the guests' ee.
Upon closer examination of the mechanism of action, it was found that several complicating factors, including prototropic tautomerism, macrocyclic inversion (ring-flipping), and 1:2 host guest stoichiometry, obstruct potential applications of OxP as a chiral solvating agent. By considering the molecular conformation of the OxP host, a saddle-shaped calix[4]pyrrole, we moved to study the tetraphenylporphyrin (TPP) dication since it has a similar form, and it was found that it could also be used to probe ee.
However, although TPP does not suffer from disadvantageous tautomeric processes, it is still subject to macrocyclic inversion and has the additional serious disadvantage of operating for ee sensing only at depressed temperatures.