Diels-Alder reactions with normal electron demand

Lewis acid catalysis enormously enriches the scope of Diels-Alder reactions, but it is limited to reagents containing Lewis basic sites, i.e. functional groups with lone pairs such as carbonyl, amino, ether or nitro close to the reaction centre. As we have seen in the discussion about the FMO aspects of Lewis acids, the major reason for catalysis is the reduction of the HOMO-LUMO gap. In case of Diels-Alder reactions with normal electron demand, it follows that the coordination of the Lewis acid lowers the LUMO energy of the dienophile. Such interactions are only possible if there is a spatial proximity or an electronic conjugation between the coordinated Lewis basic site and the reaction centre. Fortunately, in nearly every Diels-Alder reaction one of the reagents, mostly the dienophile, meets this requirement. 

Diels-Alder Reactions with Normal Electron Demand... 

Diels-Alder reactions of the type shown in Table 15.1, that is, Diels-Alder reactions between electron-poor dienophiles and electron-rich dienes, are referred to as Diels-Alder reactions with normal electron demand. The overwhelming majority of known Diels-Alder reactions exhibit such a normal electron demand. Typical dienophiles include acrolein, methyl vinyl ketone, acrylic acid esters, acrylonitrile, fumaric acid esters (irans-butenedioic... 

An increase in reactivity also can be observed in Diels-Alder reactions with normal electron demand if a given dienophile is reacted with a series of more and more electron-rich dienes. The reaction rates of the Diels-Alder reactions of Figure 15.22 show that the substituents MeO > Ph > alkyl are such reactivity-enhancing donors. The tabulated rate constants also show that a given donor substituent accelerates the Diels-Alder reaction more if located in position 1 of the diene than if located in position 2. 

Fig. 15.21. Diels-Alder reactions with normal electron demand increase of the reactivity upon addition of a Lewis acid. The AlClj complex of the acrylate reacts 100,000 times faster with butadiene than does the uncomplexed acrylate.

Fig. 15.22. Diels-Alder reactions with normal electron demand reactivity increase by the use of donor-substituted 1,3-dienes (Do refers to a donor substituent).

The first term of Equation 15.3 is responsible for most of the transition state stabilization of a Diels-Alder reaction with normal electron demand. In this case, the first term is larger than the second term because the denominator is smaller. The denominator of the first term is smaller because the HOMO of an electron-rich diene is closer to the LUMO of an electron-poor dienophile than is the LUMO of the same electron-rich diene with respect to the HOMO of the same electron-poor dienophile (Figure 15.24, column 2). Acceptors lower the energy of all 7F-type MOs irrespective of whether these MOs are bonding or antibonding. This is all the more true the stronger the substituent effects and the more substituents are present. 

We can customize these general statements specifically for the case of the regioselectivity of Diels-Alder reactions with normal electron demand and make the following statement right away ... 

Finally, the examples of the two Diels-Alder reactions in Figure 15.28 lead us to a general statement in Diels-Alder reactions with normal electron demand, the addition of a Lewis acid such as A1C13 increases the reaction rate and the regioselectivity. This is a nice example of the failure of the reactivity-selectivity principle (Section 1.7.4), which is so often used in organic chemistry to explain reaction chemistry. 

The first term of Equation 12.3 is responsible for most of the transition state stabilization of a Diels-Alder reaction with normal electron demand. In this case, the first term is larger than the second term because the denominator is smaller. The denomi-... 

Diels-Alder reactions (with normal electron demand) rely on an electron-rich diene and an electron-deficient dienophile. As aconsequence, there exist a number of impossible dienophiles one might like to use in synthesis, which turn out to have too poor reactivity in Diels-Alder cycloadditions or which participate in alternate reaction pathways. Such impossible dienophiles are CH2=CH2, RCH=CH2, CH2=C=0, HC=CH, and RC=CH — all building blocks that one really wishes to employ in the planning of a synthesis. Fortunately, a series of synthetic equivalents for these impossible dienophiles exists. They participate readily in Diels-Alder cycloadditions, though they require subsequent refunctionalization steps. The example [28] in Scheme 6.11 demonstrates that vinylsulfone CH2=CHS02Ph may serve as a synthetic equivalent for either CH2=CH2 or RCH=CH2. 

Sol 1. (a) This is an example of Diels—Alder reaction with normal electron demand. The diene is electron-rich and hence will use its HOMO for the cycloaddition, whereas, the dienophile is electron-deficient and hence will use its LUMO. 

Diels-Alder reaction with normal electron demand... 

As with butadiene, a Diels-Alder reaction with normal electron demand occurs, that is, the HOMO of furan (see Figure 5.2c) interacts with the LUMO of maleic anhydride. The reaction is diastereoselective. Alder s endo-rule applies to the stereochemistry of the cycloadducts 21/22 thus, in acetonitrile at 40°C, the mdo-adduct 21 is formed 500 times faster than the evo-adduct 22 owing to kinetic control. However, with a sufficiently long reaction time, product formation becomes subject to thermodynamic control the initially formed mdo-compound is completely converted via the educts to the exo-compound, which is more stable by 8 kj mol. ... 

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