Diastereomeric aggregates, formation

What happens for a nonracemic mixture of enantiomers Is it possible to calculate the values of the chiral properties of the solution from knowledge of the properties of the enantiopure compound In principle, yes, on the condition that there is no autoassociation or aggregation in solution. Then, the observed properties will be simply the weighted combination of the properties of two enantiomers. A nice example of where this normal law may be broken was discovered by Horeau in 1967 it is the nonequivalence between enantiomeric excess (ee) and optical purity (op, with op = [a]exi/[ ]max) for 2,2-methylethyl-succinic acid. In chloroform op is inferior to ee, while in methanol op = ee. This was explained by the formation of diastereomeric aggregates in chloroform, while the solvation by methanol suppresses the autoassociation. 

The formation of diastereomeric aggregates may perturb the achiral properties as well, when compared to homochiral solutions, since the aggregation state will be not necessarily the same. It has been observed that the NMR spectra of racemic and enantiopure dihydroquinine in chloroform are significantly different. ... 

The isolated enantiomers S (M ) and R (Mr) of a chiral molecule M exhibit the same spectral features since their physical properties are identical. However, their aggregation with a chiral chromophore of defined configuration (Cr/s) leads to the formation of two diastereomeric complexes with different spectral properties, i.e., and [C /yM ]. The lcR2PI spectroscopy is able to discriminate between Mj and by measuring the spectral shift of the diastereomeric [C /yM ] and [Cj5/5-Mj ] complexes with respect to that of the bare chromophore Cr/s- It is convenient to define the diastereomeric clusters as homochiral when the chromophore and the solvent have the same configuration, and heterochiral in the opposite case. 

The presence of a NLE may afford useful information during the study of an asymmetric catalytic reaction. It is indicative of the formation of diastereomeric species within the catalytic cycle (competing catalysts) or at the periphery of the catalytic cycle (reservoir effects). A frequently encountered situation is the for-mationof diastereomeric species by aggregation (e.g. dimerization, trimeriza-tion, etc.) of a complex. 

While the aforementioned self-dispropoitionation phenomenon is not frequently observed, it has been documented and can happen not only during the HPLC purifications, but also during the standard purifications by flash chromatography. It arises from the association of the enantiomers of chiral compounds in solution (Fig. 4). Such association results in the formation of homo- and heterochiral aggregates that are of diastereomeric nature and hence have different chromatographic properties. 

---