Self-induced nonequivalence

Partially resolved samples of certain compounds show enantiomeric NMR nonequivalence in an otherwise achiral medium, and do so in magnitudes proportional to their enantiomeric purity. This phenomenon, termed self-induced nonequivalence or autononequivalence, has been observed for compounds shown in Table 12. Dihydroquinine (44) was the first of these examples to be reported (14). Figure 6 shows portions of the 100 MHz spectra of optically pure, naturally occurring dihydroquinine, a 1 1 mixture of the natural product and synthetic racemate, and the racemate alone, all at approximately the same concentration in CDCI3 solution. The three spectra are different Figure 6b shows nonequivalence for the H2, Hy, Hg, and H9 resonances, the intensities corresponding to the optical purity of the sample (33%, e.e.). 

The dependence of this phenomenon on temperature and concentration has been studied in detail (70,71,87) and treated mathematically (87). In principle any compound capable of self-association might be capable of self-induced nonequivalence. These cases should be sufficient to suggest due caution on the part of those who would establish the identity of a racemate (e.g., a synthetic natural product ), by comparison of its NMR spectrum with that of the naturally derived optically pure substance. This phenomenon is not restricted to solutes with aromatic substituents, as evidenced by Table 12. Self-induced nonequivalence may be eliminated by addition of polar solvents or by dilution of the sample. Under these conditions, as has been shown for dihydroquinine (14), spectra of racemic, optically pure, and enriched material become identical. 

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. 

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