Diastereotopic atoms or groups

Some of the compounds shown below contain enantiotopic or diastereotopic atoms or groups. Which possess this characteristic For those that do, indicate the atoms or groups that are diastereotopic and assign the groups as pro-R and pro-S. 

Two atoms or groups are said to the diastereotopic if the two atoms or groups appear to be similar but are not actually related by a symmetry operation. Selectively labeling one diastereotopic atom or group wUl not produce the mirror image of the molecule in which the other atom or group is labeled. For example, the methylene protons in phenylalanine are diastereotopic. The resonances from diastereotopic atoms and groups will normally be anisochronous, unless they happen to fortuitously have the same chemical shift. 

Diastereotopic (Section 7 13) Descnbing two atoms or groups in a molecule that are attached to the same atom but are in stereochemically different environments that are not mirror images of each other The two protons shown in bold in H2C=CHC1 for example are diastereotopic One is cis to chlonne the other is trans... 

Compound (III)—The protons are diastereotopic. There is a chiral centre already present in this compound. In a prochiral assembly CX2WY, X atoms or groups are diastereotopic if either W or Y is chiral. 

Just as there are enantiotopic and diastereotopic atoms and groups, so we may distinguish enantiotopic and diastereotopic faces in trigonal molecules. Again we have three cases (1) In formaldehyde or acetone (G), attack by an achiral reagent A from either face of the molecule gives rise to the same transition state and product the two faces are thus equivalent. (2) In butanone or acetaldehyde (H), attack by an achiral A at one face gives a transition... 

Another example is provided by malic acid, a chiral molecule which also contains a prochiral center (see Eq. 9-74). In this case replacement of the pro-R or pro-S hydrogen atom by another atom or group would yield a pair of diastereoisomers rather than enantiomers. Therefore, these hydrogen atoms are diastereotopic. When L-malic acid is dehydrated by fumarate hydratase (Chapter 13) the hydrogen in the pro-R position is removed but that in the pro-S position is not touched. This can be demonstrated by allowing the dehydration product, fumarate, to be hydrated to malate in 2HzO (Eq. 9-74). The malate formed contains deuterium in the pro-R position. If this malate is now isolated and placed with another portion of enzyme in H20, the deuterium is removed cleanly. The fumarate produced contains no deuterium. 

Where two atoms or groups in a molecule are in such positions that replacing each of them in turn by a group Z gives rise to diastereomers, the atoms or groups are called diastereotopic. Some examples are the CH2 groups of 2-chlorobutane (97), vinyl chloride (98), and chlorocyclopropane (99) and the... 

The terms enantiotopic and diastereotopic describe the relationship between a pair of atoms or groups in a molecule. Sometimes it is also useful to describe the local environment of a single atom, group, or location in a molecule (even if it does not coincide with an atomic center) as chiral or not. A chirotopic atom or point in a molecule is one that resides in a chiral environment, whereas an achirotopic atom or point does not. All atoms and all points associated with a chiral molecule are chirotopic. In achiral molecules, achirotopic points are those that remain unchanged (are invariant) upon execution of an S that is a. symmetry operation of the molecule. For most situations, this means that the point either lies on a mirror plane or is coincident with the center of inversion of the molecule. Importantly, there will generally be chirotopic points even in achiral molecules. 

Diastereotopic are those heterotopic atoms or groups that during substitution result in a pair of diastereomers. When substimtion of two H-atoms with deuterium or another atom/ group (i.e., desymmetrization) forms diastereomers, those two H-atoms are not equivalent, and give two signals in the NMR spectmm. Several examples of organic compounds with diastereotopic atoms are provided in Figure 1.33. 

Asymmetric bond disconnection is less frequently employed than asymmetric bond formation for the synthesis of chiral, nonracemic compounds. The substrates for these transformations contain either enantiotopic (diastereotopic) hydrogen atoms or enantiotopic (diastereotopic) functional groups. In some cases the classification of a given transformation of such a substrate as asymmetric bond disconnection or bond formation is somewhat arbitrary. Thus, enantiotopic and diastereotopic group differentiation is also described at appropriate places in various sections but more specifically in part B of this volume. 

Fig. 7. Bridges containing diastereotopic atoms in Me2CH or PhCH2 groups in compounds of the type Os3H(/j-X)(CO)10.

In this review, we shall concentrate on the stereochemistry of enzymic reactions of amino acids, many of which involve transformations at prochiral centers. We shall use the nomenclature of Hanson (8) to specify the stereochemistry of prochiral atoms and groups as pro-R (Hjj) and pro-S (Hj) and of prochiral faces as Re and Si and the nomenclature of Mislow and Raban (2) to describe prochiral groups as having enantiotopic or diastereotopic relationships. Reviews on the stereochemistry of enzymic reactions of amino acids were published in 1978 (9,10), and since the seminal review by Dunathan in 1971 (11), several reviews comparing the stereochemistry of pyridoxal phosphate-catalyzed enzymic reactions have appeared (12-15). 

Pro-R. An atom or functional group that is part of an enantiotopic or diastereotopic pair that, upon (isotopic) labeling such that it acguires a higher precedence, generates an R chiral center. 

Diastereotopic hydrogens (or ligands) (Section 9.8B) If replacement of each of two hydrogens (or ligands) by the same groups yields compounds that are diastereomers, the two hydrogen atoms (or ligands) are said to be diastereotopic. 

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