Diels-Alder reaction computational model

Solvents exert their influence on organic reactions through a complicated mixture of all possible types of noncovalent interactions. Chemists have tried to unravel this entanglement and, ideally, want to assess the relative importance of all interactions separately. In a typical approach, a property of a reaction (e.g. its rate or selectivity) is measured in a laige number of different solvents. All these solvents have unique characteristics, quantified by their physical properties (i.e. refractive index, dielectric constant) or empirical parameters (e.g. ET(30)-value, AN). Linear correlations between a reaction property and one or more of these solvent properties (Linear Free Energy Relationships - LFER) reveal which noncovalent interactions are of major importance. The major drawback of this approach lies in the fact that the solvent parameters are often not independent. Alternatively, theoretical models and computer simulations can provide valuable information. Both methods have been applied successfully in studies of the solvent effects on Diels-Alder reactions. 

With ever more powerful technology becoming available, computer-based molecular modeling of complex chemical reactions is now commonplace. But while the Diels-Alder reaction has received a great deal of theoretical attention, the dipolar cycloaddition reactions of nitrones were until very recently relatively... 

The computer generated model in Figure 1.6 shows the perfect fit of the exo-adduct inside the 2,2,2-trimer cavity. The smaller 1,1,2-trimer showed a stereoselective bias towards the endo-product at 30 °C however, this stereoselectivity is lost at higher temperatures (a mixture of both the endo- and exo-products was observed at 60 °C). The reversal of the stereochemical outcome of the Diels-Alder reaction between the two cyclic dimers (30 °C) appears to lie firstly in a large (500-fold) endo acceleration... 

However, a computational study124 shows that the Kishi model controls the stereoselectivity for (Z)-alkenes. Note also that in the Diels-Alder reactions of hexachloropentadiene with chiral alkenes, the inside alkoxy effect is attributed to electrostatic repulsion of the oxy group in the125 outside position with the chlorine atom of hexachloropentadiene in the 1-position. 

Alder reaction route, since the computation data indicate that the transition state model of Diels-Alder reaction is 17.7 and 12.1 kcal/mol higher in free energy (AG) than those of the Michael and aldol reactions, respectively, and they indicated that the Michael-aldol... 

This report stimulated considerable discussion among theoretical chemists. Borden and co-workers reported results of ab initio calculations indicating that the Diels-Alder reaction is, in fact, a synchronous reaction. These authors indicated, however, that this result was obtained "only when a flexible basis set is used and when electron correlation is properly treated." Otherwise, a nonsynchronous process was observed. Bemardi and coworkers also reported ab initio evidence for a S5mchronous Diels-Alder reaction. Houk and co-workers reported experimental evidence that the Diels-Alder reaction is concerted and is most likely synchronous as well. These authors also pointed out that different computational methods have built-in biases toward different transition structures. This controversy reminds us that, as noted before, computational methods should be considered as useful tools that are developed from particular conceptual models and not as windows into reality. ... 

One of the most important aspects of the Diels-Alder reaction is the understanding of the factors infiuencing the endolexo stereoselectivity. To analyse the origin of the Diels-Alder stereoselectivity, the [4+2] cycloaddition of furan and maleic anhydride has been studied experimentally for many years as an interesting model system and revisited computationally by Calvo-Losada and Suarez. At the MP2/6-31G level the electron density of the endo has an additional RCP and a CCP. 

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