Substituent effect, additivity explanation

It is often difficult to understand at an intuitive level the explanation for the effect of changing substituents on the rate constant ratio kjkp for partitioning of carbocations between nucleophilic addition of solvent and deprotonation. In these cases, insight into the origins of the changes in this rate constant ratio requires a systematic evaluation of substituent effects on the following ... 

Bromination of Aromatic Rings 593 Other Aromatic Substitutions 597 Alkylation of Aromatic Rings The Friedel-Crafts Reaction Acylation of Aromatic Rings 604 Substituent Effects in Substituted Aromatic Rings 605 An Explanation of Substituent Effects 610 Trisubstituted Benzenes Additivity of Effects... 

Any explanation of facial selectivity must account for the diastereoselection observed in reactions of acyclic aldehydes and ketones and high stereochemical preference for axial attack in the reduction of sterically unhindered cyclohexanones along with observed substituent effects. A consideration of each will follow. Many theories have been proposed [8, 9] to account for experimental observations, but only a few have survived detailed scrutiny. In recent years the application of computational methods has increased our understanding of selectivity and can often allow reasonable predictions to be made even in complex systems. Experimental studies of anionic nucleophilic addition to carbonyl groups in the gas phase [10], however, show that this proceeds without an activation barrier. In fact Dewar [11] suggested that all reactions of anions with neutral species will proceed without activation in the gas phase. The transition states for reactions such as hydride addition to carbonyl compounds cannot therefore be modelled by gas phase procedures. In solution, desolvation of the anion is considered to account for the experimentally observed barrier to reaction. 

However, a discussion of the behaviour of level is difficult due to the complex variations which may occur in the P-N fragment. In addition to the determining effect of phosphorus hybridization the coupling is sensitive to the planarity at the nitrogen and when comparing substituent effects possible concomitant changes in the various conformational equilibria must be considered. In spite of these difficulties, satisfactory explanations of the behaviour of in limited series can be proposed and several types of correlation... 

The changes in the values of ks/kp observed for partitioning of the carbocations R-[14+] (Table 3) requires that the addition of a-ester, a-amide and a-thioamide substituents result in different changes in ks and kp for partitioning of the parent l-(4-methoxyphenyl)ethyl carbocation.33,41 42 The explanation for the changes in these ratios is complex, and is most easily understood by separate considerations of the effects of these substituents on ks and kp (Scheme 11). 

The explanation of the regiospecificity of Diels-Alder reactions requires knowledge of the effect of substituents on the coefficients of the HOMO and LUMO orbitals. In the case of normal electron demand, the important orbitals are the HOMO on the diene and the LUMO on the dienophile. It has been shown that the reaction occurs in a way which bonds together the terminal atoms with the coefficients of greatest magnitude and those with the coefficients of smaller magnitude [18]. The additions are almost exclusively cis and with only a few exceptions, the relative configurations of substituents in the components is kept in the products [19]. 

Cyclohexanones in which the chair inversion is constrained by substitution undergo diastereoselective nucleophilic addition, the nature of which (i.e., preferentially axial or preferentially equatorial) depends on the nature of the substituents. The explanation of this effect has been extensively explored [95, 189, 193-197]. The simplest explanation, shown in Figure 8.5, involves a distortion of the carbonyl group from planarity in such a way as to improve 71-type donation from the ring C— bond or the axial bond (often a C—H bond) in the a position, whichever is the better donor. A secondary effect is the improved interaction between the distorted n orbital and the HOMO of the... 

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