Use of sub-stoichiometric amounts of chiral auxiliaries for enantiodifferentiation by NMR; caveats and potential utility

Chemical shift (δ) order reversal of the population-weighted averaged NMR signals for enantiomers when using sub-stoichiometric levels of a chiral auxiliary (CA) can occur when the δ difference between the enantiomer-CA complexes and the signal of the free enantiomers is greater for the less-stable complex. The potential utility of CA titration curves with regard to ΔG evaluation, configuration determination, and modeling validation is considered.