Stereochemistry of 1 reaction

Reactions belonging to the same reaction type are projected into coherent areas on the Kohonen map this shows that the assignment of reaction types by a chemist is also perceived by the Kohonen network on the basis of the electronic descriptors. This attests to the power of this approach. 

There are finer details to be extracted from such Kohonen maps that directly reflect chemical information, and have chemical significance. A more extensive discussion of the chemical implications of the mapping of the entire dataset can be found in the original publication [28]. Gearly, such a map can now be used for the assignment of a reaction to a certain reaction type. Calculating the physicochemical descriptors of a reaction allows it to be input into this trained Kohonen network. If this reaction is mapped, say, in the area of Friedel-Crafts reactions, it can safely be classified as a feasible Friedel-Qafts reaction. 

A wider variety of reaction types involving reactions at bonds to oxygen atom bearing functional groups was investigated by the same kind of methodology [30]. Reaction classification is an essential step in knowledge extraction from reaction databases. This topic is discussed in Section 10.3.1 of this book. 

Many chemical reactions proceed with a clearly defined stereochemistry, requiring the bonds to be broken and made in the reaction to have a specific geometrical arrangement. This is particularly true for reactions that are controlled by enzymes. 

The stereochemistry of reactions has to be handled in any detailed modeling of chemical reactions. Section 2.7 showed how permutation group theory can be used to represent the stereochemistry of molecular structures. We will now extend this approach to handle the stereochemistry of reactions also [31]. 

A similar change in product, this time dependent on temperature, takes place in the substitution of ammonia for both chlorides in [Co(en)2Cl2]. At low temperatures (-33° C or below, in liquid ammonia), there is inversion of configuration at higher temperatures (above 25° C in liquid ammonia, alcohol solution, or solid exposed to gaseous ammonia), there is retention. In both cases, there is also a small fraction of the trans isomer. 

Although not a complete explanation of these reactions, all the reported inversion reactions occur under conditions in which a conjugate base mechanism is possible. The orientation of the ligand entering the proposed trigonal-bipyramidal intermediate 

FIGURE 12-7 Mechanisms of Base Hydrolysis of A-ds-[Co(en)2Cl2]. (a) Retention of configuration in dilute hydroxide, (b) Inversion of configuration in concentrated hydroxide. 

Source Data from F. Basolo and R. G. Pearson, Mechanisms of Inorganic Reactions, 2nd ed., J. Wiley Sons, New York, 1967, p. 257. 

Dissociative mechanisms lead to products where the stereochemistry may be the same or different than the starting complex. Table 12.9 shows that cw-[Co(en)2L(H20)] is a hydrolysis product of both ct5 -[Co(en)2LX] and trfl 5-[Co(en)2LX] in acid solution. While these aquation reactions with pure ci5-[Co(en)2LX] lead exclusively to cis products, retention of the trans ligand orientation in fra 5-[Co(en)2LX] depends on both L andX. The conjugate base mechanism is unlikely in these reactions they are carried out in acidic solution. 

In Table 12.9, the starting ds-[Co(en)2LX] are racemic mixtures of A-cw-[Co(en)2LX] + and A-cd-[Co(en)2LX] , and the product mixtures, while exclusively cis, are also racemic. A related study (Table 12.10) employed optically pure A-c -[Co(en)2LX] + for reactions with hydroxide, where a conjugate base mechanism is possible. This reaction resulted in cis prodnct with partial racemization of the stereochemistry, as well as some trans product (% trans = 100% — % cis). When the optically inactive tra i-[Co(en)2LX] + is used, varying yields of cis isomers are formed as racemic mixtures. 

Up to this point, we have emphasized the stereochemical properties of molecules as objects, without concern for processes which affect the molecular shape. The term dynamic stereochemistry applies to die topology of processes which effect a structural change. The cases that are most important in organic chemistry are chemical reactions, conformational changes, and noncovalent complex formation. In order to understand the stereochemical aspects of a dynamic process, it is essential not only that the stereochemical relationship between starting and product states be established, but also that the spatial features of proposed intermediates and transition states must account for the observed stereochemical transformations. 

In describing the stereochemical features of chemical reactions, we can distinguish between two types stereospecific reactions and stereoselective reactions. A stereospecific reaction is one in which stereoisomeric starting materials aflFord stereoisomerically different products under the same reaction conditions. A stereoselective reaction is one in which a single reactant has the capacity of forming two or more stereoisomeric products in a particular reaction but one is formed preferentially. 

The stereochemistry of the most fundamental reaction types such as addition, substitution, and elimination are described by terms which specify the stereochemical relationship between the reactants and products. Addition and elimination reactions are classified as syn or anti, depending on whether the covalent bonds which are made or broken are on the same face or opposite faces of the plane of the double bond. 

While it may be convenient to use optically active reactants to probe the stereochemistry of substitution reactions, it should be emphasized that the stereochemistry of a reaction is a feature of the mechanism, not the means of determining it. Thus, it is proper to speak of a substitution process such as the hydrolysis of methyl iodide as proceeding 

Mander, Stereochemistry of Organic Compounds, John Wiley Sons, New York, 1993, p. 837. 

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The stereochemistry of reactions can also be treated by permutation group theory for reactions that involve the transformation of an sp carbon atom center into an sp carbon atom center, as in additions to C=C bonds, in elimination reactions, or in eIcctrocycHc reactions such as the one shown in Figure 3-21. Details have been published 3l]. 

The stereochemistry of reactions can be treated by means of permutation group theory. 

The term syn addition describes the stereochemistry of reactions such as this m which two atoms or groups add to the same face of a double bond When atoms or groups add to opposite faces of the double bond the process is called anti addition... 

Elucidating the stereochemistry of reaction at prochirality centers is a powerful method for studying detailed mechanisms in biochemical reactions. As just one example, the conversion of citrate to (ds)-aconitate in the citric acid cycle has been shown to occur with loss of a pro-R hydrogen, implying that the reaction takes place by an anti elimination mechanism. That is, the OH and H groups leave from opposite sides of the molecule. 

A detailed discussion of the different acidities of the diastereotopic a-methylene protons in sulphoxides, as well as of the stereochemistry of reactions of sulphoxide a-carbanions with electrophilic reagents is beyond the scope of this chapter. A recent review by Wolfe pertinent to these problems is available392. 

For a review of the stereochemistry of reactions in which a carbon-transition metal a bond is formed or broken, see Flood, T.C. Top. Stereochem., 1981, 12, 37. See also Ref. 11. 

Recently Kernaghan and Hoffmann (175a) have investigated the stereochemistry of reaction of cis and trans 1-phenylethenyl bromide, 180. Upon stirring of 180a or 180b with silver trifluoroacetate in isopentane at room... 

Stereochemical Control Through Reaction Conditions. In the early 1990s it was found that the stereochemistry of reactions of boron enolates of N-acyloxazolidinones can be altered by using a Lewis acid complex of the aldehyde or an excess of the Lewis acid. These reactions are considered to take place through an open TS, with the stereoselectivity dependent on the steric demands of the Lewis acid. With various aldehydes, TiCl4 gave a syn isomer, whereas the reaction was... 

Flood, Thomas C., Stereochemistry of Reactions of Transition Metal-Carbon Sigma Bonds, 12, 37. Floss, Heinz G., Stereochemistry of Biological Reactions at Proprochiral Centers, 15, 253. Freedman, T. B., Stereochemical Aspects of Vibrational Optical Activity, 17, 113. 

Green) Stereochemistry of Reactions of Transition Metal-Carbon Sigma Bonds 9 35... 

The COX reaction is quite remarkable. Arachidonic acid has no chiral centers, but PGE2 and PGI2 have four and TxB2 has five The immediate product of the COX reaction, known as PGH2, also has five chiral centers. This is an elegant example of the ability of enzymes to control the stereochemistry of reactions. 

The hydroxyl group in /raw.v-cycloocten-3-oI determines the stereochemistry of reaction of this compound with the Simmons-Smith reagent. By examining a model, predict the stereochemistry of the resulting product. 

The stereochemistry of reactions at zinc atoms has been studied in small molecules (Auf der Heyde and Nassimbeni, 1984) and in proteins (Holmes and Matthews, 1981 Vallee and Auld, 1990a,b). Zinc enzymes include carboxypeptidase A (Quiocho and Lipscomb, 1971 Rees et al., 1983), in which the zinc is coordinated to two histidine nitrogen atoms, two glutamate oxygen atoms, and water (involved in hydrolysis) (Fig. 26). 

Biirgi, H.-B. (1975). Stereochemistry of reaction paths as determined from crystal structure data—A relationship between structure and energy. Angew Chem., Int. Ed. Engl. 14, 460-473. 

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