Diels-Alder reaction activation barriers

Calculate activation energies for the three Diels-Alder reactions (energy of transition state - sum of energies of reactants). Which reaction has the smallest energy barrier Which has the largest energy barrier Do your results parallel the measured relative rates of the same reactions (see table at left) ... 

The retro Diels-Alder reaction usually requires high temperatures in order to surmount the high activation barrier of the cycloreversion. Moreover, the strategy of retro Diels-Alder reaction is used in organic synthesis to mask a diene fragment or to protect a double bond [47]. Some examples are illustrated in Scheme 1.11. 

The first examples of transition metal-catalyzed [5 + 2]-cycloadditions between vinylcyclopropanes (VCPs) and 7r-systems were reported in 1995 by Wender and co-workers.10 This [5 + 2]-reaction was based conceptually on the Diels-Alder reaction, replacing the four-carbon, four-7r-electron diene with a five-carbon, four-electron VCP (Scheme 1). Although the [5 + 2]-reaction of VCPs and 7r-systems can be thought of as a homolog of the Diels-Alder [4 +21-reaction, the kinetic stability of VCPs (activation barrier for the thermal isomerization of VCP to cyclopentene has been reported as 51.7 kcal mol-1)11 makes the thermal [5 + 2]-reactions involving VCPs and 7r-systems very difficult to achieve. A report of a thermal [5 + 2]-cycloaddition between maleic anhydride and a VCP has been published,12 but this reaction has not been reproduced by others.13 14 Based on the metal-catalyzed isomerization of VCPs to cyclopentenes and dienes,15-20 Wender and co-workers hypothesized that a metal might be used to convert a VCP to a metallocyclohexene which in turn might be trapped by a 7r-system to produce a [5 + 2]-cycloadduct. Based on its previous effectiveness in catalyzed [4 + 2]-21 and [4 + 4]-cycloadditions (Section 10.13.2.4), nickel(0) was initially selected to explore the potential of VCPs as four-electron, five-carbon components in [5 + 2]-cycloadditions. 

Additionally, investigations into imidazolidinone catalysed Diels-Alder reactions (Schemes 2 and 6) [234] have shown that iminium ions of a,P-unsaturated aldehydes and ketones have lower activation barriers for the Diels-Alder reaction with cyclopentadiene than the parent compound (13 and 11 kCal mol", respectively). It was also noted that transition structures show the formation of the bonds is concerted but highly asynchronous. 

In the case of the above-mentioned Diels-Alder reactions, the reactant conformers are separated by energy barriers which are far smaller than the activation required for cycloaddition. 

We first take up the issue of computing the activation barrier for this parent Diels-Alder reaction. Rowley and Steiner experimentally determined an activation barrier of 27.5 0.5 kcal mol for Reaction 4.1. Using thermal corrections computed at B3LYP/6-31G, Houk and coworkers estimate that Alfi(0 K) =... 

Bach, R. D. McDouall, J. J. W Schlegel, H. B. Electronic factors influencing the activation barrier of the Diels-Alder reaction. An ab initio study, J. Org. Chem. 1989, 54, 2931-2935. 

High pressure has been applied successfully to Diels-Alder reactions of furans, which are notoriously troublesome due to low activation barriers and low or even negative AC values. For example, attempts to synthesize the potent vesicant cantharidin (232) via reaction of furan (228) with dimethylmaleic anhydride (234) date back to 1928. The failure of this approach has been attributed to a thermodynamic preference for cycloreversion over cycloaddition. More than SO years later the problem was solved by employing high pressures and either a modified dienophile (229) or diene paitner (233). Interestingly, product (235) reverts to reactants (233) and (234) in solution at atmospheric pressure and room temperature (Scheme S4). 

The barrier to converting the s-trans conformation to the s-cis conformation contributes to the overall activation barrier for Diels-Alder reactions. Structural factors that increase the proportion of diene in its s-cis conformation increase the rate of the Diels-Alder reaction, and factors that increase the proportion of diene in its s-trans conformation decrease the rate of the reaction. Cyclopentadiene is one of the best dienes for the Diels-Alder reaction partly because it cannot rotate out of its s-cis conformation. In fact, cyclopentadiene undergoes [4 + 2] cycloaddition to itself so readily that it lasts only a few hours at 0 °C. o-Xylylenes are especially good dienes both because of their enforced s-cis geometry and because a nonaromatic starting material is transformed into an aromatic product. By contrast, dienes in which one of the double bonds is cis are poor substrates for Diels-Alder reactions because steric interactions between the in substituents in the s-cis conformation are particularly severe, and dienes whose s-trans conformation is enforced do not ever undergo the Diels-Alder reaction. 

Bimolecular reactions involve a collision between two molecules, with enough energy to overcome the activation barrier. These processes are usually concerted, with bond formation and breaking taking place simultaneously. The relative orientation is important, so that the new bonds can be formed between atoms that are near enough to each other. Reactions (1.1a) and the first step of (1.7b) are examples of bimolecular reactions. Reaction (1.10) is an example of a bimolecular reaction that does not involve ions. Three covalent bonds are broken and formed synchronously, and Diels Alder reactions of this type are very useful... 

Ab initio calculations and experimental measurements suggest that coordination of an a,P-unsatuxated carbonyl to a Lewis acid results in an increase in the barrier to rotation about the Cj-C2 single bond from 4-9kcal/mol to 8-12 kcal/mol as a result of augmented Cj-C2 double bond character (Fig. 13) [33]. This energy barrier is in the same regime as the measured energy of activation for a typical catalyzed Diels-Alder reaction. 

There is no doubt that the driving force for cyclopropene as the dienophile for a Diels-Alder reaction is the release of angle strain energy in the course of the reaction. This is demonstrated by its relatively low activation barrier. For example, cyclopropene reacts with cyclopentadiene and butadiene at 0°C or at room temperature, producing almost exclusively the endo cycloadduct [53]. This addition can be explored by computing activation barriers for two isomeric transition state structures. In this way, nonbonding interactions between diene and dienophile in two isomeric transition state structures can be closely evaluated. The reactivity and selectivity for two concurrent reaction pathways can also be computed. 

Table 9. Activation barrier for Diels-Alder reactions with heterocycles as dienes computed using the AMI semiempirical (AEj) and B3LYP/6-31G(d)//AM (AEn)...

Table 13. Computed activation barriers for Diels-Alder reactions reaction species HOF E AEi...

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