Diastereomeric relationships

The synthesis in Scheme 13.38 is based on an interesting kinetic differentiation in the reactivity of two centers that are structurally identical, but diastereomeric. A bis-amide of we.w-2,4-dimethylglutaric acid and a chiral thiazoline was formed in Step A. The thiazoline is derived from the amino acid cysteine. The two amide carbonyls in this to-amide are nonequivalent by virtue of the diastereomeric relationship established... 

The inherent difficulty in analyzing enantiomers arises from the well-known fact that apart from their chiroptical characteristics, optical isomers have identical physical and chemical properties in an achiral environment (assuming ideal conditions). Therefore, methods of distinguishing enantiomers must rely on either their chiroptical properties (optical rotation, optical rotatory dispersion, circular dichroism), or must employ a chiral environment via diastereomer formation or interaction. Recently, it has become increasingly clear that such diastereomeric relationships may already exist in nonracemic mixtures of enantiomers via self-association in the absence of a chiral auxiliary (see Section 3.1.4.7.). 

The threo and erythro designation denotes a diastereomeric relationship of the isomers. Each tlireo and erythro isomer will also have enantiomers which will also have a direo-erythro diastereomeric relationship to each other. 

Glyceraldehyde, of which 107 and 109 arc protected forms, is the only three-carbon sugar. There are two four-carbon sugars erythrose 111 and threose 113. Both exist in hemiacetal (furanose) and open chain forms and both are chiral but their symmetry properties differ. The tetrols formed by reduction of the aldehydes are me so erythritol 112 and C2 symmetric threitol 114 having the same stereochemistry as tartaric acid 35. Threose or threitol can be oxidised to tartaric acid. These sugars are the origin of the terms erythro and three sometimes used to describe such diastereomeric relationships. 

Remote diastereomeric relationships can be controlled by using enantiomerically pure components when it is impossible to control them by diastereoselective reactions. 

A frans-decalin system can be produced by using a substrate with the opposite diastereomeric relationship (Eq. 56 and Fig. 10) [17]. Of interest is the heightened stereoselectivity observed when the relatively rigid cyclohexane unit is substituted for the fluxional cyclopentane moiety (Eq. 54). This rigidity accentuates the steric interactions governing the stereochemical course of the reaction. 

Let us consider two achiral stereoisomers (2 and 3) shown in Fig. 10.2. They are also stereoisomeric to 1 and 1 shown in Fig. 10.1. By the above definitions, the relationship between 1 and 2 (or 3) is concluded to be diastereomeric, because the enantiomer 1 is different to the achiral 2. On the other hand, the relationship between the achiral 2 and 3 is also concluded to be diastereomeric, because their mirror images (2 and 3 themselves) are different to each other. It should be noted, however, that the diastereomeric relationship between 1 and 2 is different from the diastereomeric relationship between 2 and 3 in whether there exist enantiomeric relationships or not. 

From another point of view, an isomerization fi om 1 (chiral) to 2 (achiral) is different from an isomerization from 2 (achiral) to 3 (achiral), where both of the isomerizations correspcaid to the above-mentioned diastereomeric relationships of different types. Hence, we should say that there exist at least two diastereomeric relationships of different types. The conventional stereochemistry is silent about such diastereomeric relationships of different types. In other words, the dichotomy between enantiomers and diastereomers in the conventional stereochemistry is oversimplified. 

It should be emphasized that diastereomeric relationships of the conventional terminology are not pairwise relationships, whereas / S-diastereomeric (or holantimeric) relationships of the present terminology are pairwise relationships. This fact is a succinct piece of evidence for stating that the conventional dichotomy between enantiomers and diastereomers are oversimplified. 

It should be emphasized that reflection operations are conceptually independent of f 5-permutation operations. The criteria collected in Table 10.1 indicate that a pair of chirality/achirality as attributes is conceptually independent of a pair of l S-stereogenicity// 5-astereogenicity and that enantiomeric relationships are independent of / 5-diastereomeric relationships. Hence, the stereoisogram of Type I provides us with a new viewpoint to prevent the conventional dichotomy between enantiomers and diastereomers ... 

In the present stereoisogram approach, the / 5-diastereomer (7 = 7) of 7 is conceptually different from the enantiomer (7) of 7, even if they are identical with each other. The / 5-diastereomeric relationship between 7 and 7 (= 7) is recognized to be superposable on the enantiomeric relationship between 7 and 7. This conceptual feature is emphasized by the recognition of the self-holantimeric relationship between 7 and 7 (= 7) or between 7 and 7 (= 7). 

In cOTtrast, the enantiomeric relationship between 7 and 7 is preferred in the conventional approach of stereochemistry. Once the relationship between 7 and 7 has been recognized as being enantiomeric, the f S -diastereomeric relationship between 7 and 7 (= 7) is neglected, i.e., recognized not to exist under the dichotomy between enantiomers and diastereomers . 

As a result, the conventional dichotomy between enantiomers and diastereomers is concluded to be misleading, because it neglects f S -diastereomeric relationships which are superposable on enantiomeric relationships (Fig. 10.4). 

Fig. 10.5 shows a stereoisogram concerned with 1 and 1 shown in Ing. 10.1. They appear in the left-hand vertical direction, which shows the enantiomeric relationship between 1 and 1. The stereoisogram (Fig. 10.5) is characterized by the presence of self-f 5-diastereomeric relationships and referred to as belonging to Type 11. The discussions described in Sect. 10.2.1 are more clearly demonstrated by means of the stereoisogram shown in Fig. 10.5. The stereoisogram index [—,a, —] for a Type II stereoisogram sequentially indicates chirality, / 5-astereogenicity, and sclerality.

According to the stereoisogram approach. Type V cases (e.g.. Fig. 10.2) are recognized to be named by the CIP system by virtue of f 5-diastereomeric relationships on the same line as Types 1 and 111. For example, a pair of f 5-diastereomers 2 and 3 located at the horizontal S-axis of Fig. 10.8 is characterized by a pair of f 5-stereodescriptors in terms of such a common priority sequence asa>b>p>p (tentatively specified for the sake of explanation). 

By virtue of the dichotomy between enantiomers and diastereomers in the conventional approach. Type I cases prefer enantiomeric relationships to rationalize l S -stereodescriptors of the CIP system, as found in Table 10.3. In other words, the conventional approach exclusively takes account of the vertical C-axis of Fig. 10.4 and results in the neglect of the horizontal S-axis, which causes systematic neglect of l 5-diastereomeric relationships. Accordingly, l 5-stereodescriptors are presumed to be given to an enantiomeric pair of promolecules 7 and 7 by applying such as a priority sequence a > b > X > Y. Fortunately, in the Type I cases, the priority sequence (a > b > X > Y) for the... 

Type V cases are named by the CIP system by virtue of diastereomeric relationships (Table 10.3), because Type V cases are concerned with achiral (self-enantiomeric) promolecules and lack enantiomeric relationships within the conventional terminology. Type V cases of the conventional approach are in the same situations as the present approach (e.g., Fig. 10.8), if the diastereomeric relationships are interpreted in terms of the I 5-diastereomeric relationships of the present approach. 

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