Chromatographic Enantioseparations in Achiral Environments: Myth or Truth?

Direct chromatographic enantioseparations are among the most important practical tasks of chromatography. The accepted rules and concepts of stereochemistry anticipated one type of chromatographic systems applicable only to such enantioseparations consisting either of chiral stationary phase, or chiral selector present in mobile phase. In such a model of chromatographic system, both racemic and non-racemic mixtures could be enantioseparated. Over the years, however, reports on successful chiral enantioseparations in non-chiral chromatographic systems have cumulated as well. To adapt the initial model to novel experimental evidence, an assumption had to be added stating that these were only non-racemic mixtures (and not racemic ones), which could be enantioseparated in achiral chromatographic systems, by granting them an inevitable chirality from the enantiomeric excess of a more abundant enantiomer. There still exists an overlooked portion of experimental evidence for successful enantioseparations of racemic mixtures in the non-chiral chromatographic systems, which cannot be explained by the accepted model. Facing this incompatibility between the model and practical results, we reflect on how to reconcile these two by questioning the possibility of pinpointing a true racemate with the help of our imperfect analytical tools.