Diastereomeric interaction

NMR spectroscopy cannot normally be used directly for discriminating enantiomers in solution. The NMR signals for most enantiomers are isochronic under achiral conditions. However, NMR techniques can be used for the determination of enantiomer compositions when diastereomeric interactions are introduced to the system. 

Nuclear Magnetic Resonance Spectroscopy Measured in a Chiral Solvent or with a Chiral Solvating Agent. One method of NMR analysis for enantiomer composition is to record the spectra in a chiral environment, such as a chiral solvent or a chiral solvating agent. This method is based on the diastereomeric interaction between the substrate and the chiral environment applied in the analysis. 

The application of a chiral auxiliary or catalyst, in either stoichiometric or catalytic fashion, has been a common practice in asymmetric synthesis, and most of such auxiliaries are available in homochiral form. Some processes of enantiodifferentiation arise from diastereomeric interactions in racemic mixtures and thus cause enhanced enantioselectivity in the reaction. In other words, there can be a nonlinear relationship between the optical purity of the chiral auxiliary and the enantiomeric excess of the product. One may expect that a chiral ligand, not necessarily in enantiomerically pure form, can lead to high levels of asymmetric induction via enantiodiscrimination. In such cases, a nonlinear relationship (NLE) between the ee of the product and the ee of the chiral ligand may be observed. 

Figure 1. Schematic relationship of enantiomeric and diastereomeric interactions for two pairs of enantiomers.

When the analyte is chiral, however, the stereochemical issues evolve to how a chiral host interacts with a chiral guest. The nature and magnitude of these diastereomeric interactions ultimately control the DCL evolution and what types of hosts are amplified. 

The influence of the chiral solvent is ascribed to the unequal diastereomeric interactions between the chiral medium and enantiomeric forms of solutes. This concerns not only the cis-syn conformers (P and M) of the parent compound in the ground-state, but also in the excited-state, and even the enantiomeric DHP s belonging to... 

Diastereomeric interaction between molecules of the racemic mixture and the chiral chromatography medium causes enantiomers of the racemate to move through the stationary phase at different rates. 

Catalytic Enantioselective Alkylation / 258 Diastereomeric Interaction of Enantiomers / 278 Effects on Solid-State Properties / 279 Effects in Solution / 281 References / 293... 

An alternative and very direct approach is to separate the enantiomers on a column in which the stationary liquid phase is a chiral compound. The diastereomeric interaction is between A+ or A and the chiral liquid phase, and may be sufficiently different to permit separation of A+ from A. The ratio of the amounts of A+ and A corresponds to the enantiomeric purity. 

The potential perturbations afforded by diastereomeric interactions between enantiomers during reactions were pointed out by Wynberg and Feringa in 1976.24 They stated that when a chiral substance undergoes a reaction, the reaction rate and the product ratio will depend—inter alia—upon the enantiomeric excess present in the starting material. ... 

Cyclodextrins (CDs) are chiral compounds which interact with enantiomers via diastereomeric interactions. The separation is achieved because of the difference in stabilities of the resulting diastereomeric complexes formed between each enantiomer and the CD. In the first CEC experiments incorporating CDs, di-methylpolysiloxane containing chemically bonded permethylated (3- or y-CD (Chirasil-DEX) was chemically bonded to the inner walls of fused silica capillaries [139,140]. Electoosmotic flow is generated in these capillaries in the same manner as in fused silica capillaries. The Chirasil-DEX does not mask all the silanol groups, so while EOF is decreased, it is not entirely diminished by the coating. Since that time, CDs or CD derivatives have been bonded to silica particles which were then packed into capillaries, and the CD has been incorporated into continuous polymer beds known as monoliths. Table 3 shows some different CSPs, enantiomers separated, resolution, and the number of theoretical plates per meter. 

Li and Lloyd were among the first to report the use of immobilized proteins as a CSP in CEC [141]. They packed silica particles derivatized with ar acid glycoprotein (AGP) into CE capillaries. Chiral sites are present in the peptide sequence of AGP, as well as in the carbohydrate units present. The presence of the chiral centers sets up the same type of diastereomeric interactions as with CDs, as well as a host of other interactions such as hydrogen bonding. At the... 

It is conceivable that in such an arrangement unfavourable diastereomeric interactions can arise at the R)- S) contacts which account for the metastability of the completely disordered phase. We tried then to reduce the number of unwanted (/ )-(5) contacts by intercalating molecules of (2) with, for example, the isopropyl homo-... 

Firstly, one can use a "chiral solvating agent (CSA) in which one relies on diastereomeric interactions, or complexations, to give a chemical shift difference for the two enantiomers. The method was first used to demon- 01... 

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