Diastereotopic nuclei

NMR spectroscopy the enantiomers are converted into a pair of diastereomers by chemical reaction with an auxiliary (enantiomerically pure, chiral compound) and the ratio of the peak areas of nonequivalent externally diastereotopic nuclei is measured by NMR. 

On the timescale of the NMR experiment, isochrony (chemical shift equivalence) arises from symmetry equivalence of homotopic and enantiotopic nuclei5 17, while anisochrony (chemical shift nonequivalence, JK s <5) arises from symmetry nonequivalence of diastereotopic nuclei. 

It is important to note that enantiotopic nuclei, i.e., nuclei that are related by reflection symmetry, are rendered diastereotopic in a chiral environment. Thus, in contrast to homotopic nuclei, i.c., nuclei that are related by an axis of rotation, isochronous (enantiotopic) nuclei can be transformed into anisochronous (diastereotopic) nuclei via desymmetrization with chiral reagents or in chiral environments. 

The geometry of the resulting diastereomeric association complexes is distinct and diastereotopic nuclei reside in different spatial environments. In this case the sense of nonequivalence would not necessarily be the same for all shifted resonances, but reversals could be expected. 

Table 5. H and T Chemical Shift Differences for Diastereotopic Nuclei in ATEA36 Derivatives...

The immediate cause for anisochrony is, of course, the unequal magnetic field sensed by the diastereotopic nuclei. It follows that as the source of the diastereotopic environment is removed further and further from the test nuclei, the anisochrony is expected to diminish. This prediction has been tested 43> with the results shown in Table 1. 

As the last example of coalescence of signals of diastereotopic nuclei due to site exchange in solution we present the case of the Schiff base of a-naphthyl isopropyl ketone and benzylamine (106, Fig. 49)" . This molecule possesses a prochiral axis by virtue of the fact that coplanarity of the C=N double bond with the naphthalene ring leads to strong steric interactions the coplanar conformation... 

Bonded to a group that withdraws part of the electron density from around the nucleus. The absorptions of deshielded nuclei are moved downfield, resulting in larger chemical shifts, (p. 568) Nuclei that occupy diastereomeric positions. The replacement test for diastereotopic atoms gives diastereomers. Diastereotopic nuclei can be distinguished by NMR, and they can split each other unless they are accidentally equivalent, (p. 592)... 

Therefore, the two circled hydrogens in 4-9 are said to be diastereotopically related, or simply diastereotopic. They are not equivalent. And this relationship persists even though rotation of the C -C bond is fast on the NMR time scale. Here is the all-important bottom line While NMR normally cannot distinguish between enantiotopic nuclei (but see Section 10.7.3), NMR can distinguish between diastereotopic nuclei (at least in principle). 

EXAMPLE 4.6 (a) Indicate all homotopic nuclei, enantiotopic nuclei, and diastereotopic nuclei in structure 4-10. You may assume rapid rotation of all bonds, (b) How many H and 13C NMR signals would you predict for the compound ... 

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