Induced anisochrony

In the latter case, the applicability rests on a knowledge of the relative formation constants of homo- or heterochiral diastereomers. A special case arises when the formation of dimers occurs by self-association (being fast on the NMR timescale) under nonideal conditions leading to nonequivalence of resonance absorptions. When the enantiomeric composition differs from that of the racemic mixture, self-induced anisochrony is observed and the intensities of the signals are directly related to the enantiomeric ratio regardless of parameters such as temperature, concentration, and the ratio of homo- and heterochiral dimers116. 

CSA (Chiral solvating agent) A diamagnetic additive of known enantiomeric purity used to induce anisochrony in enantiomers of a racemate for NMR analysis. See Section 2.3.4. 

Two possible mechanisms have been suggested as the source of AA5 Kr Ks, or (+)-CSR R and (+)-CSR S have different geometries [58]. It is likely that both of these mechanisms operate to differing extents in various systems. Regarding Kr and Ks, note that nuclei that are enantiotopic by internal comparison, such as the methylene protons of benzyl alcohol or the methyls of dimethyl sulfoxide, can be differentiated by CSRs [59]. Clearly no stability difference is required for inducing anisochrony. An important consequence of this fact is that the enantiomeric purity of compounds that are chiral by virtue of isotopic substitution (e.g., CgHsCHDOH) may be evaluated by this method (as well as by the CSA method described in the next section). 

Note the distinction between the terms shift reagent and solvating agent. Because of the differences in the mechanism of binding and induced anisochrony, the former is reserved for lanthanide complexes and the latter for diamagnetic compounds. 

As with CSRs, both enantiomers should be available to insure the presence of induced anisochrony. ... 

As was the case with chiral shift reagents, preferential population of one diastereomer over the other (Kr Ks) is not a prerequisite for induced anisochrony of enantiotopic groups. Additionally, since the CSA is diamagnetic, it may be used in excess over the analyte. A five-fold excess is usually sufficient to drive the equilibria of Equation 2.16 to the outside, such that the solute is present only as its two diastereomeric solvates. Since the observed spectra are time-averages of all the species in solution, this chemical trick simplifies analysis of absolute configuration by focussing on the diastereomeric solvates alone. 

In principle, induced anisochrony could also be established by studying an enantiomerically pure analyte with racemic CSA cf. Figure 2.5). 

For the analysis of compounds that are chiral by virtue of isotopic substitution, NMR is the method of choice, since energetic differences between diastereomeric complexes are not required for induced anisochrony. When it works, NMR is also one of the simplest and fastest techniques available. For monofunctional or weakly basic solutes, chiral shift reagents are more likely to succeed, whereas chiral solvating agents are simpler (when they work) and are better for the assignment of absolute configuration. 

Anisochrony in CSAs is usually induced in enantiotopic groups of a ligand by the presence of an anisotropic moiety in the CSA, such as an aromatic ring (as opposed to a paramagnetic metal atom). 

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