Reactivity in the Diels-Alder Reaction

Diels-Alder reactions of cyclopentadiene with different alkenes proceed at different rates. Cyclopentadiene reacts with acrolein in ether at room temperature (24 h) to give a 95% yield of 27.59 contrasts with the reaction of cyclopentadiene and ethene in ether to give a 74% yield of norbornene (28), but required heating to 200°C in an autoclave at 5800 psi pressure or 32 h. The presence of an electron releasing group on the alkene causes the reaction to proceed with greater difficulty. Vinyl acetate reacted with cyclopentadiene at 190°C in an autoclave (10 h, neat) to give only 25% of 29. 

The first term in Equation 11.1 is the Coulomb integral, 3b apj apj gj f e total charges on atoms k and I e is the local dielectric constant is the distance between atoms k and 1 Cf-a is the coefficient of atomic orbitals (a) in molecular orbital (r), where r refers to the molecular orbitals on one molecule and s refers to those on the other and Ef and Eg are the energies of the molecular orbitals. 

To conclude this section, it is important to note that alkenes are not the only hydrocarbon dienophiles that are useful partners in the Diels-Alder reaction. Alkynes and even benzyne are quite useful. As a structure proof of an intermediate in Pandey s synthesis of epiboxidine, the methyl carbamate of pyrrole (34) reacted with dimethyl-2-butynoate (35),in the presence of aluminum chloride (see sec. 11.6.A for a discussion of Lewis acid catalysis) to give a 90% yield of azanorbomadiene (36). A benzyne derivative of pyridine was 

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Rank the following dienophiles in order of their expected reactivity in the Diels-Alder reaction. 

Inner-outer-ring dienes are very useful in the synthesis of polycyclic molecules. Their reactivity in the Diels-Alder reaction depends on the type of ring (carbo-cyclic, heterocyclic, aromatic) that bears the ethenyl group or on the electronic effects of substituents at the diene moiety [30]. 

For a review of reactivity in the Diels-Alder reaction, see Konovalov, A.I. Russ. Chem. Rev, 1983, 52, 1064. 

For a review of reactivity in the Diels-Alder reaction, see Konovalov Russ. Chem. Rev. 1983, 52, 1064-1080. For a review of Diels-Alder reactions with cyclic enones, see Fringuelli Taticchi Wcnkert Org. Prep. Proced. Int. 1990, 22, 131-165. 

The chemical reactivity of (1) and (2) is a dichotomy. Benzenoid character is indicated in normal electrophilic substitution (nitration, sulfonation and catalyzed halogenation, Section 4.26.4.1) and in the lack of dienophile reactivity in the Diels-Alder reaction. On the other hand, typical dienoid character is exhibited in the facile ozonolysis of the benzene ring of (1) and in the easy, non-catalyzed tetra-addition of halogen (see Section 4.26.4.1). 

Because cyclopentadiene is fixed in the. v-cis conformation, it is highly reactive in the Diels-Alder reaction. It is so reactive, in fact, that at room temperature, cyclopentadiene slowly reacts with itself to form dicyclopentadiene. Cyclopentadiene is regenerated by heating the dimer above 200 °C. At this temperature, the Diels-Alder reaction reverses, and the more volatile cyclopentadiene monomer distills over into a cold flask. The monomer can be stored indefinitely at dry-ice temperatures. 

When cis- 1,3-pentadiene rotates to the s-cis conformation, a steric interaction occurs between the methyl-group protons and a hydrogen on Cl. Since it s more difficult for cis-1,3-pentadiene to assume the s-cis conformation, it is less reactive in the Diels-Alder reaction. 

The aromaticity of a heterocycle depends on how effectively the lone-pair of the heteroatom contributes to the aromatic sextet. The aromaticity of five-membered heterocyclic compounds may be estimated from their reactivity in the Diels-Alder reaction.94 Spectrophotometry shows that furan, thiophene, and selenophene resemble benzene in that with maleic anhydride 1 1 complexes are formed which are stable up to 150°C in the case of thiophene, decompose at 150°C with selenophene (whereby selenium is formed together with a diene which gives a further adduct with another molecule of maleic anhydride), and produce the usual adduct at 20°C with furan. Thus, only furan is a normal diene as regards the Diels-Alder reaction. 

The counterion in these complexes plays a significant role for both catalyst activity and reaction enantioselectivity (eq 5). The hexafluoroantimonate-derived complex is 20 times more reactive in the Diels-Alder reaction than its triflate counterpart. This discovery resulted in a significantly broader scope (e.g. 1,3-cyclohexadiene, furan, isoprene and many other dienes can also be used successfully) of the reaction. The crystalline aquo com-... 

Felber, H, Kresze, G, Prewo, R, Vasella, A, Diastereoselectivity and reactivity in the Diels-Alder reactions of a-chloronitroso ethers, Helv. Chim. Acta, 69, 1137-1146, 1986. 

In order to achieve the necessary geometry in the Diels-Alder transition state, the diene must be able to adopt the 5-cis conformation. In Section 10.10, we saw that the s-cis conformation of 1,3-butadiene is 12 kJ/mol (2.8 kcal/mol) less stable than the 5-trans form. This is a relatively small energy difference, so 1,3-butadiene is reactive in the Diels-Alder reaction. Dienes that cannot readily adopt the s-cis conformation are less reactive. For example, 4-methyl-1,3-pentadiene is a thousand times less reactive in the Diels-Alder reaction than ra/25-1,3-pentadiene because its 5-cis conformation is destabilized by the steric effect imposed by the additional methyl group. 

Sample Solution (a) The first dienophile has two carbonyl groups attached to the double bond, which make it more reactive in the Diels-Alder reaction. In the second dienophile, these two carbons are CH2OH carbons, which are not activating. 

Cyclic dienes yield bridged bicyclic Diels-Alder adducts. Since they are constrained to the 5-cis conformation, cyclic dienes such as 1,3-cyclopentadiene are highly reactive in the Diels-Alder reaction. 

The FMO model is also valuable in rationalizing several observations about relative reactivities in the Diels-Alder reaction. Reactivity is enhanced with electron-withdrawing groups on the olefin, as shown by the data in Table 11.5 for reaction of cyclopentadiene with cyano-substituted alkenes. Reactivity is also enhanced by any electron-donating groups on the diene, as shown by the data in Table 11.6 for the reaction of some dienes with tetr acy anoethy lene. 

Cyclic dienes in which the double bonds are held in the s-cis conformation are usually highly reactive in the Diels-Alder reaction. Cyclopentadiene, for example, reacts with maleic anhydride at room temperature to give the following adduct in quantitative yield ... 

Sol 14. The double bonds of the cyclopentadiene are held in the s-cis conformation. This makes the cyclopentadiene so reactive in the Diels—Alder reaction that it dimerizes at room temperature. One molecule acts as the diene and the other as the dienophile to form dicyclopentadiene. The dicyclopentadiene formed has the ring of dienophile in an endo orientation to the cyclopentadiene ring that acts as the diene. Usually, substituents on the dienophile are found to be endo in the adduct if the substituents contain the 7T-bonds due to favorable secondary interactions. 

Phenyl l,2,4-triazoline-3,5-dione, is an extremely reactive dienophile and enophile that is at least 1000 times more reactive in the Diels-Alder reaction with 2-chlorobutadiene than tetracyanoethylene (TONE) and 2000 times more reactive than maleic anhydride. 4-Methyl-1,2,4-triazoline-3,5-dione, 2, is at least 30,000 times more reactive towards cyclohexene than its open chain analog, ethylazodicarboxylate. The many reactions of these powerful electron-acceptor molecules are generally quite rapid, being complete within a matter of seconds within the range of 0 C to room temperature. 

The structural modification of the cyclic 1,3-diene system of Phase I afforded novel noncyclic bis(1,3-diene)s of varying reactivity in the Diels-Alder reaction with bismaleimides. Low to high molecular weight polyimides were prepared from the noncyclic bis(1,3-diene) systems and bis(4-maleimidyl-phenyl)methane, which exhibited better solubility in organic solvents than the Phase I system. Moderate thermal stability was observed by TGA for these polymers. 

As anticipated, these destabilized benzenes are much more reactive in the Diels-Alder reaction than their undistorted relatives (Fig. 14.11). 

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