Differentiation ofmeso isomers from racemic mixtures with the combined use of chiral shift reagents and two-dimensional heteronuclear correlation NMR spectroscopy

In the presence of chiral shift reagents the enantiotopic nuclei of a pair of enantiomers become diastereotopic and have the potential to give resolved NMR signals. Similarly, the enantiotopic nuclei within a meso isomer become diastereotopic in the presence of a chiral shift reagent acid may give resolved NMR signals, However, the diastereotopic nuclei of a meso isomer mixed with a chiral shift reagent, unlike those of a racemic mixture, are located in the same molecule. Their intramolecular character can be established experimentally by detection of spin-spin splitting between them or to a common third nucleus. Comparison of the correlation peaks in a two-dimensional, heteronuclear, multiple-quantum correlation (HMQC) spectrum with those of a heteronuclear multiple-bond correlation (HMBC) spectrum is an effective means of detection of coupling to a third nucleus. Two-dimensional NMR spectroscopy was used to identify the meso form of di-(trans-2-aminocyclohexyl)amine.