Electrophilic aromatic substitution computations

The mechanism of direct arylation has been studied experimentally and computationally and possible pathways include electrophilic aromatic substitution, Heck-type coupling and concerted metalation-deprotonation (CMD). The reaction pathway is dependent on the substrate and the catalytic system employed,however, most electron-rich (hetero)arenes seem to follow a base-assisted CMD pathway. Two catalytic cycles for the coupling of bromo-benzene and thiophene are shown in Schemes 19.5 and 19.6. Scheme 19.5 depicts a carboxylate-mediated process where C-H activation occurs... 

Electronic effects in conjugated systems may be computed with the Hiickel HMO method. Electron densities are used to predict aromatic substitution reactions, and it is possible to refer to radical, nucleophilic, and electrophilic localization energies.For the latter, the term ELENERGY is used in a transform, for example IF ELENERGY ON ATOM 1 BETTER THAN ATOM 2 THEN ADD 20. 

As mentioned in Section 2, there have been many general calculations on the charge densities of aromatic heterocyclic systems, and these results have been used to make predictions about substitution patterns. In addition, studies of electrophilic substitutions of some heterocycles have used computational methods to predict not only the orientation but also the reactivity and stereospecificity of the substitution."... 

A review has been published regarding computational studies of arenes, linear polycyclic aromatics, and their reactivities in electrophilic and nucleophilic processes. There have also been reviews of theoretical studies of electron delocalization and its relevance to electrophilic substitution, and of mechanisms of activation of carbon-hydrogen bonds to reactions with electrophiles. ... 

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