Enantiotopic and Diastereotopic Protons

Consider ethanol (key sentence coming up). If you were to replace each of the methylene protons in turn with some other group, Z, you would end up with a pair of enantiomers. We call this, the Z test. For this reason, the protons (or whatever groups may be involved, in molecules of the type X-CA2-Y) are described as enantiotopic. This is of no consequence in the spectrometer, because as we have mentioned, enantiomers are not distinguishable by NMR under normal conditions. 

The molecule clearly does not contain any chiral centres and so should give a perfectly straightforward spectrum. Now take a look at the Spectrum 6.5. 

Some confusion can arise over use of the term prochiral to describe various sites within molecules and is perhaps best avoided for this reason. The term means literally, one step removed from being chiral (i.e., swap one of the protons for Z and you have a full chiral centre). The methylene in ethanol for example, would be a good example. What we have in the di-ethoxy molecule above is one prochiral centre acting in combination with another to render a pair of protons non-equivalent. 

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Enantiotopic and diastereotopic protons and groups are discussed in Chapter 32, p. 000. 

For each compound given below (a-o), describe all spin systems (using Pople notation where appropriate), chemically shift equivalent protons, magnetic equivalent protons, enantiotopic protons, and diastereotopic protons. 

Understanding enantiotopic and diastereotopic relationships is essential in the interpretation of NMR spectra. Enantiotopic protons are equivalent in... 

It should be noted that the vinyl and methyl proton resonances of the Z-isomer [i.e., of the achiral tetracarbonylirondimethyl (Z)-butenedioate complex] are also discriminated in the presence of Eutbfc), because the internally enantiotopic nuclei are rendered diastereotopic in the presence of the nonracemic LSR81. The vinyl protons of the. E-isomer show two lines (external diastereotopism) while the vinyl protons of the Z-isomer exhibit an AB-system (internal diastereotopism)5. 

Label the pairs of protons shown in boldface in each of the following compounds as homotopic, enantiotopic, or diastereotopic, as required. Assume normal rotational barriers and observations at room temperature. 

In favorable circumstances, active (or dl) and meso stereoisomers may be distinguished directly an acyclic (84) and a cyclic (85) example are shown in Fig. 34. In both cases the methylene protons Hc in the active forms are related by a C2 axis and therefore homotopic and isochronous whereas the corresponding protons HA and Hb in the meso forms are not related by either C2 or a and are therefore diastereotopic and anisochronous. The situation is not altered when the dl form rather than an active isomer is compared with the meso form the (internally homotopic) methylene protons of the two enantiomers are externally enantiotopic and so remain isochronous. 

An alternative means for distinction of meso forms and t//-pairs 6l) is depicted in Fig. 36. Benzylation of the amines 88 and 89 gives the N-benzyl derivatives 90 and 91. In 90, derived from the meso isomer 88, HA and HB are enantiotopic and hence isochronous they constitute a single (A2) signal. In contrast, in 91, derived from the active isomer or d/-pair 89, the benzylic protons are diastereotopic and hence anisochronous and constitute an AB system. 

What we have said so far explains to you why homotopic and enantiotopic groups appear identical in the NMR spectrum, but diastereotopic protons may not. Now we will give a quick guide to determining what sort of pair you are dealing with in a given molecule. 

Finally, for the other molecules, mentally replace each of the two hydrogens in the indicated set with X, a different group. In (a), the resulting products are enantiomers, and the protons are enantiotopic. Replacement of the protons in (b) produces two chirality centers (the carbon bearing the hydroxyl group is now chiral) and the indicated protons are diastereotopic. Replacement of one of the methyl protons in each of the groups in (c) produces a pair of double-bond isomers that are diastereomers these protons are diastereotopic. The protons in (f) are homotopic. 

Characterize the indicated protons as (1) homotopic, enantiotopic, or diastereotopic and (2) magnetically equivalent or nonequiva lent (by the coupling-constant criterion). In parts (h) and (i), the Cr(CO)3 ligand remains on one side of the benzene ring. 

As an example of a molecule with diastereotopic ligands, consider the amino acid L-phenylalanine. The two protons at C-3 are diastereotopic, since substitution of either of them would generate a molecule with two chiral centers. Because the chiral center already present is 5, the two diastereomers would be the 2S,3R and the 25,35 stereoisomers. As in the case of enantiotopic protons, diastereotopic protons are designated pro-R or pro-S. The enzyme phenylalanine ammonia lyase catalyzes the conversion of phenylalanine to trans-cinnamic acid by a process involving anti elimination of the amino group and the 3-pro-S hydrogen. This stereochemical course has been demonstrated using deuterium-labeled L-phenyl-alanine as shown" ... 

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