Topicity Relationships

Table 2. Prostereogenic Units and Topic Relationships of Constitutionally F.quivalent Groups...

Molecular fragments, like whole molecules, may display steric relationships, as pioneered by Hanson [20] and Mislow [18]. When such fragments are considered in isolation, namely separated from the remainder of the molecule, morphic relationships arise. When the partial structures are considered in an intact molecule or in different intact molecules, one speaks of topic relationships. 

Topic relationships are of fundamental importance when considering prostereoisomerism, and they will be discussed again and illustrated in this context (see Section 7). 

This section discusses the relationships between groups or atoms of same constitution within intact molecules (topic relationships). Such intramolecular relationships are of fundamental importance in understanding stereochemical aspects of en-... 

Three criteria are useful when assessing topic relationships, namely (a) the molecular environment, (b) symmetry considerations, and (c) the substitution criterion. When two topic groups in a molecule have stereoisomeric environments, the molecule is said to possess elements of prostereoisomerism. Mislow and Raban have given a definitive classification of topic relationships [62], and the following discussion is based on this classification. 

In determining selectivity in ligogenic processes (Chapter 9), the center of attention is usually on either whole molecules Sj vs. S2, or, molecular sites tj vs. t2. In the former instance, one deals with morphoselectivity - selectivity based on morphic relationships between molecules in contrast, in the latter instance, one invokes situselectivity - selectivity based on topic relationships between molecular sites. In this chapter we deal with morphoselectivity situselectivity is treated in the next chapter. The concept of morphoselectivity is synonymous with substrate selectivitystructural selectivity," intermolecular selectivity," shape selectivityand, enzyme substrate selectivity it is also implicit in intermolecular chemoselectivity. This chapter deals with the concept of morphoselectivity, and establishes the commonality of all the above literature terms. 

In a chemical transformation of a molecule with two reactive sites (or subsites) tj and t2, it is the topic relationship between the two sites (or subsites) (Volume 1, Chapter 3, p. 35) that determines the exact type of situselectivity (vide infra). If tj and t2 are stereotopic with respect to each other, then the process is characterized by stereosituselectivity (stereotopic site selectivity) if the sites are nonstereotopic, then one has nonstereosituselectivity (nonstereotopic site selectivity). Stereosituselectivity is subclassified into enantiosituselectivity (enantiotopic site selectivity) or diastereosituselectivity (diastereotopic site selectivity), if ti and t2 are enantiotopic, or, diastereotopic with respect to each other, respectively.On the other hand, nonstereosituselectivity is subclassified into astereosituelectivity (nonstereotopic site selectivity) or nonequisituselectivity (nonstereotopic site selectivity), depending on whether ti and t2 are astereotopic, or, nonequitopic with respect to each other, respectively. Figures 11.5 and 11.6 illustrate select examples of stereosituselectivity and nonstereosituselectivity. 

The complete classification of the different types of selectivity is given in Figure 11.7. Such a classification enables one to specify the type of situselectivity at the level of detail needed or desired. At the simplest level, a process at a molecular site is selective (situselective), nonselective (situnonselective), or aselective (situaselective). If situselective, a process is either stereosituselective or nonstereosituselective. At the next level, one may specify the topic relationship between the sites - enantiosituselective vs. diastereosituselective, or astereosituselective vs. nonequisituselective. The next level of detail specifies the type of site... 

Topic Relationship of Sites t,and t t, 2 Achiral Influence/Medium Chiral Influence/Medium ... 

Stereotopicity and chirotopicity are deemed independent attributes of molecular sites - be it ligands, bonds, molecular faces or molecular segments. The former attribute is defined by a specific topic relationship between two given sites, whereas the latter attribute describes the chirality/achirahty of the molecular field. Indeed, two molecular sites are, with respect to one another, either stereotopic or nonstereotopic, irrespective of the achirality/chirality of the molecule in which they are situated. Conversely, a molecular site is either achirotopic or chirotopic, regardless of any stereotopic or nonstereotopic relationship(s) it may bear with respect to another (or other) intramolecular site(s). 

To ensure uniformity of designations, we consider the two half-spaces, defined by a planar functional group at a given site in the molecule, as sub-sites. In turn, these sub-sites also bear a (stereo)topic relationship with respect to each other. 

We then broach situselectivity (selective reaction at molecular site ti over molecular site t2) and classify it on the basis of the topic relationships of reacting sites (Chapter 11). Where the focus of attention is on site selectivity, we emphasize that the correct term should be situselectivity and not oft-misused and -abused term regioselectivity. We also discuss bisituselectivity for transformations involving two reactant molecules/moieties each with its own preferred site of attack. 

Figure 10.3 summarizes topicity relationships in the conventional terminology of stereochemistry. The two achiral ligands X s in 4 (the ligands a and b are also achiral in isolation) are enantiotopic to each other, while the two achiral ligands X s in 5 (a achiral, p chiral in isolation) as well as the two achiral ligands X s in 6 (p and p enantiomeric in isolation) are diastereotopic to each other. The difference between the enantiotopic X s in 4 and the diastereotopic X s in 5 (or 6) stems from difference in their substitution products (enantiomers vs. diastereomers ). 

In accord with Table 10.1, three topic relationships and the corresponding attributes are collected in Table 10.2. Note that the term holantitopic does not appear in usual situations because such a process as Type 1 ([—, —, a]) to Type 111 is usually regarded as a process of another f 5-stereogenic center and because a promolecule [, , — ] generated from Type IV [a, a, a]) is... 

Table 10.4 Three topic relationships and the corresponding attributes, which are characterized by stereoisograms for testifying prochirality and/or pro-/ 5-stereogenicity (Fujita 2009c) ...

Synthetic chemists are continually in search of new methods to control the stereochemical outcome of synthetic transformations. Although the exact methods used are best described in textbooks with a focus upon asymmetric synthesis, it is worth mentioning here how sophisticated the field is becoming. By analyzing how the topicity relationships within reactants will influence enantiomeric and disastereomeric selectivities, a multitude of reactions with good stereochemical control have been developed. One particular example that highlights just how far advanced... 

Topicity relationships and symmetry arguments provide a powerful approach to anticipating reactivity patterns. Whether by habit, intuition, or full realization, it is the topicity relationships discussed above that synthetic chemists use to develop chemical transformations that yield asymmetric induction. 

Supporting Text How Did We Get Here reviews previously introduced concepts, mathematical tools, and topical relationships that the new chapter will draw on. 

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