Enantiotopic 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. 

If the test ligands are chiral, the products of replacing first one and then the other of two enantiotopic ligands by them will be diastereomeric. Similar considerations apply to addition of chiral ligands to enantiotopic faces. 

View of the rest of the molecule from each enantiotopic ligand... 

Enantiotopic ligands and faces are not interchangeable by operation of a symmetry element of the first kind (Cn, simple axis of symmetry) but must be interchangeable by operation of a symmetry element of the second kind (cr, plane of symmetry i, center of symmetry or S , alternating axis of symmetry). (It follows that, since chiral molecules cannot contain a symmetry element of the second kind, there can be no enantiotopic ligands or faces in chiral molecules. Nor, for different reasons, can such ligands or faces occur in linear molecules, QJV or Aoh )... 

The symmetry planes (a) in molecules 30, 32, 34, 36, 38, Fig. 13 should be readily evident. It is possible to have both homotopic and enantiotopic ligands in the same set, as exemplified by the case of cyclobutanone (34) HA and HD are homotopic as are HB and Hc, HA is enantiotopic with HB and Hc HD is similarly enantiotopic with Hc and HB. The sets HAjB and HC>D may be called equivalent (or homotopic) sets of enantiotopic hydrogen atoms. The unlabeled hydrogens at position 3, constitutionally distinct — see Section 3.4 — from those at C(2, 4), are homotopic with respect to each other. Enantiotopic ligands need not be attached to the same atom — viz. the case of mew-tartaric acid (32) and also the just-mentioned pair Ha, Hc [or Hb, Hd] in cyclobutanone. 

Symmetry elements of the second kind other than ct may generate enantiotopic ligands. Thus compound 42 in Fig. 16 (F and T are enantiomorphic, i.e. mirror-... 

Fig. 16. Enantiotopic ligands in molecules with center or alternating axis of symmetry...

Constitutionally heterotopic ligands are in principle always distinguishable, just as constitutional isomers are. Diastereotopic and enantiotopic ligands or faces may be lumped together under the term stereoheterotopic just as diastereomers and enantiomers are both called stereoisomers. 

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>. 

The compound /3-phenylglutaric anhydride, 49, contains enantiotopic ligands. On reaction with ( —)-a-phenylethylamine the two diastereoisomers of the monoamide, 50 and 51, were formed in unequal amounts [67]. In contrast to the earlier statement (the products are usually enantiomers in an enantiodifferentiating process), the products here are diastereoisomers. Of course, if the amine component of the amide were to be removed, the products from the substrate anhydride would be enantiomers. This differentiation between enantiotopic groups was important in the early days of the citrate story. It proved the possibility of differentiation in homogeneous solution, presumably without a three-point attachment. 

Figure 5. Desymmetrization of C2v symmetry by pair-wise substitution of enantiotopic ligands.

Enantiotopic ligands definition, 359 Enantio-zeroplane definition, 359 endo/exo-Selective reactions ... 

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. 

Enantiotopic atoms or groups are equivalent in all chemical respects except toward a chiral reagent. An important enzymic reaction that discriminates between enantiotopic ligands is the oxidation of ethanol catalyzed by liver alcohol... 

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