Nucleophilic attack fundamental principles

In Chapter 24, we examine carbonyl condensations—that is, reactions between two carbonyl compounds—a second type of reaction that occurs at the a carbon of a carbonyl group. Much of what is presented in Chapter 24 applies principles you have already learned. Many of the reactions may look more complicated than those in previous chapters, but they are fundamentally the same. Nucleophiles attack electrophilic carbonyl groups to form the products of nucleophilic addition or substitution, depending on the structure of the carbonyl starting material. 

Cycloadditions to [6,6]-double bonds of Cjq are among the most important reactions in fullerene chemistry. For a second attack to a [6,6]-bond of a C q monoadduct nine different sites are available (Figure 10.1). For bisadducts with different but symmetrical addends nine regioisomeric bisadducts are, in principle, possible. If only one type of symmetrical addends is allowed, eight different regioisomers can be considered, since attack to both e - and e"-positions leads to the same product. Two successive cycloadditions mostly represent the fundamental case and form the basis for the regioselectivity of multiple additions. In a comprehensive study of bisadduct formations with two identical as well as with two different addends, nucleophilic cyclopropanations, Bamford-Stevens reactions with dimethoxybenzo-phenone-tosylhydrazone and nitrene additions have been analyzed in detail (Scheme 10.1) [3, 9, 10]. 

To predict which of the two alkyne carbons, C or C, HNC will preferentially attack, one now invokes the local HSAB principle [119], which says that interaction is favored between electrophile/nucleophile (or radical/radical) of most nearly equal softness. The HNC carbon softness of 1.215 is closer to the softness ofC (1.102) than that of (0.453) of the alkyne, so this method predicts that in the reaction scheme above the HNC attacks C in preference to C, i.e. that reaction should occur mainly by the zwitterion A. This prediction agreed with that from the more fundamental approach of calculating the activation energies as the difference of ttansition state and reactant energies. This kind of analysis worked for -CH3 and -NH2 substituents on the alkyne, but not for -F. 

When the epoxide substrate is nonsymmetrical, then, in principle, two regioisomers can be formed (Figure 9.75). In both regioisomers, the stereochemistry of the incoming nucleophile and the OH is trans clearly both processes are fundamentally 5 2 in character and go with inversion of stereochemistry. With good nucleophiles, under basic conditions, the reaction is straightforward as in most 5 2 reactions, attack takes place predominantly or exclusively at the less hindered of the two carbon atoms of the epoxide. Examples are shown in Figure 9.76. 

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