Diastereotopic ligands

Just as one divides stereoisomers into two sets, enantiomers (Greek enantios = opposite) and diastereomers, so it is convenient to divide heterotopic (non-equivalent) groups or faces into enantiotopic and diastereotopic moieties. Enantiotopic ligands are ligands which find themselves in mirror-image positions whereas diastereotopic ligands are in stereochemically distinct positions not related in mirror-image fashion similar considerations relate to planes of double bonds. 

The earlier mentioned criteria may also be employed to spot diastereotopic ligands, i.e. ligands which find themselves in a stereochemically distinct but non-mirror-... 

Just as chiral centers can be labeled if or S not only in enantiomers but also in many diastereomers, so the designations pro-R and pro-S are not confined to enantiotopic ligands but may also be used for a number of diastereotopic ones (for exceptions, see below). Thus, for example, the labeling in Fig. 13 is such that HA (compounds 30, 32, 34, 36) or Me1 (compound 38) is the pro-R group the reader should verify this proposition. The same is true for compounds 46 and 5(5 in Fig. 18. Compounds 48, 50, 52 and 54 in Fig. 18 cannot be labeled in this manner since replacement of the diastereotopic ligands does not produce chiral products. In 54 (pro-pseudoasymmetric center) the substitution gives rise to a pseudoasymmetric center which, in the compound of the left is s, in the compound on the right r. Hence HA is called pro-r and HB pro-s 6>. 

In Chapter 32, the students find that what they have learned about stereoselectivity and stereospecificity applies not only to stereochemically different molecules, but also to stereochemically different parts of the same molecule. They find that portions of a molecule may be stereochemically equivalent or non-equivalent, and that they must be able to distinguish between these if they are to understand subjects as widely different as NMR spectroscopy and biological oxidation and reduction. They must leam the concepts of enantiotopic and diastereotopic ligands and faces. 

In each of molecules i and ii in Figure C.l, nuclei a are homotopic in molecule iii, they are enantiotopic and, in iv and v, they are diastereotopic. And yet, enantiotopic ligands a in iii, and diastereotopic ligands a in v, are currently designated by the same pro-R/pro-S prochirality descriptors. Furthermore, different notations are used for diastereotopic ligands of v (pro-R/pro-S), on the one hand, and diastereotopic ligands of iv pro-r/pro-s), on the other. In all the above cases, the existing notations are based on prochirality descriptors. 

Further, in the case of molecules vi and vii, nuclei a are homotopic in viii, they are enantiotopic and in ix and x, they are diastereotopic. And yet, the same pro-E/pro-Z notation is used to designate enantiotopic ligands a in viii, and diastereotopic ligands a in ix and x. Here, the designations utilize prostereotopicity descriptors. Finally, there is no descriptor for homotopic ligands in vi and vii. 

It should be noted that the two X s can be named by the pro-Rlpro-S system, where the capability of giving pro-R/pro-S-deschptors is ascribed to the pro- 5-stereogenicity. A pair of pro-R/pro-S-de,schptors is assigned to such a pair of 5-diastereotopic ligands, as shown in Figs. 10.7 and 10.13. 

Chemical differences between diastereotopic ligands are readily observable. The protons adjacent to sulfoxide groups undergo base-catalyzed hydrogen deuterium exchange in deuterated solvents easily. In benzyl methyl sulfoxide, the... 

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" ... 

Prochiral. A group is prochiral if it contains enantiotopic or diastereotopic ligands or faces, such that replacement of one ligand or addition to one face produces a stereocenter. See Section 6.3.2. 

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