Diels-Alder Reactions

55. The Diels-Alder dimerization of cyclopentadienones has been well studied. A recent paper reports experimental work and molecular mechanics calculations on the dimerization of compound 1 where both R's are methyl, both are ethyl, or one is methyl and one ethyl. To make your calculation more manageable, compute the MMX energy of the dimer of tetramethyl compound 2a, of dimethyldiethyl compound 2b, and of the four possible dimers of trimethylethyl compound 2c. Compare the energy trends in your answers with those obtained experimentally and computationally for the dimers of 1.

62. Intramolecular Diels-Alder reaction of a thia-substituted acyclic triene can give either a fused or bridged bicyclic structure; each of these can have either cis or trans stereochemistry. Calculate the energies of the four possible product structures and compare your heats of formation with those in the cited reference. Also, calculate the energy of the reactant, and estimate delta H for the reaction.

87. Cycloreversion reactions are well-known processes in organic chemistry. Use molecular mechanics to calculate delta H for the retro reactions of the carbocyclics having X = CH₂: (1) cyclohexane to three ethenes; (2) cyclohexene to 1,3-butadiene plus ethene (a retro Diels-Alder reaction); and (3) bicyclo[4.1.0]heptane to 1,4-pentadiene plus ethene; discuss the factors which are responsible for the quite different delta H values obtained. Then, do calculations on the reversions of the three compounds with X = N in which the nitrogens are connected by a double bond (i.e., azo compounds); in these cases, molecular nitrogen is produced in place of ethene; compare these three values with one another and with those for the carbocyclic compounds; discuss why delta H is so different for these azo compounds and for the corresponding hydrocarbons.

148. [4]- Radialene is the nickname for tetra methylene cyclobutane. Consider the [4]-radialene derivative shown here; it is capable of giving two different Diels-Alder adducts with, for example, ethene. Compute the energy and structure of the reactant, of the adducts shown, and of the analogous pair of adducts from reaction with ethyne. In fact, only one mode of Diels-Alder reaction occurs, as revealed in the article; justify this in terms of your calculations.

164. When the 2,3-disubstituted cyclobutadiene (E = ester) is generated, a Diels-Alder dimer A, trimer B, and tetramer C are formed in 55% overall yield. To simplify this MMX problem, let E = H (i.e., the parent compounds). Do calculations on syn structure A and on its anti stereoisomer. Also do calculations on various stereoisomers of B and C. Discuss the factors that lead to differential strain among the isomers.

167. Two 2:1 Diels-Alder adducts are formed from the reaction of cyclopentadiene with a synthon of cyclopentadienone (see the literature reference for details). In fact, four isomers having cis ring fusions at the two five-ring/six-ring junctures are possible. Do calculations on all four structures; explain why only two are actually formed; discuss why the four structures differ in stability.

168. The intramolecular Diels-Alder reaction shown below can give any or all of four diastereomeric products. After removal of the silyl group, it was found that the E-alkene gave two products whereas the Z-alkene gave two others. Do MMX calculations on all four of these isomers. Use your data to rationalize the fact that the E-isomer gives approximately a 50/50 mixture whereas the Z gives a very unequal mixture.

184. The unsaturated compound to the right has the carbon skeleton of several known intramolecular Diels-Alder adducts (see the cited reference). This MMX problem asks you to address the question of strain energy of this and related compounds (see the second structure, X = CH₂, CH₂CH₂, CH₂CH₂CH₂ as well as compounds where there is no bridging atom X and where there are two closely situated methyl groups at the position occupied by X). Determine the structures, energies, strain energies, and distance between the internal H's; discuss the effect of structure on strain energy.

200. Shown to the right is [2.2.2]triblattanetriene, a molecule that has recently been prepared as a pure enantiomer. Compute its structure and energy as well as those of its potential pyrolysis products via (1) retro [2 + 2 + 2] conversion of three sigma-bonds into pi-bonds and (2) retro Diels-Alder reaction; compare your results with those reported in the reference. Also compute the heat of hydrogenation for one, two, and three moles of H₂, eventually producing triblattane (see Problem No. 75); comment on any trends observed.

210. Isodicyclopentadiene (1) undergoes Diels-Alder reactions with a variety of dienophiles exclusively from the more hindered side of the diene (syn to the CH₂CH₂ bridge). Various explanations have been offered for this. Compounds 2 and 3 have recently been studied as a test of the various explanations. Do MMX calculations on all three compounds (do your calculations on both the chair and boat conformations for 3) and on the derivative of 3 in which its boat conformation is enforced by a CH₂CH₂ link between the unique carbons of the boat. Discuss these structures in terms of relative strain, steric ease of approach of dienophiles, etc.

216. The Diels-Alder reaction is one of the most important that conjugated dienes undergo. In order to take part, however, the diene must rotate from its usually more stable transoid to its cisoid conformation. A recent article describes the reaction of various methyl-substituted dienes with (CF₃)₂C=C(CN)₂: reaction from the transoid conformation proceeds via a zwitterion intermediate to a [2+2] cycloadduct; reaction from the cisoid proceeds in concerted fashion to the [4+2] (Diels-Alder) product. Do MMX calculations on both conformations of: 1,3-butadiene itself; (E)- and (Z)-1,3-pentadiene (R₁ = Me or R₂ = Me); 4-methyl-1,3-pentadiene (R₁ = R₂ = Me); and 2,4-dimethyl-1,3-pentadiene (R₁ = R₂ = R₃ = Me). Your calculation should include the relative energies of the conformations as well as the diene's ability to adopt an all-planar conformation. Use your calculations to comment on issues raised in the article, such as why all of the compounds enumerated above give only [4+2] reaction except for 4-methyl-1,3- pentadiene which gives exclusive [2+2].

222. Cyclopentadienes tethered to alkenes are known to give intramolecular Diels-Alder reactions. Consider the case where the tether is (CH₂)₃. When such an alkyl- substituted cyclopentadiene is prepared, a very rapid transfer of H from one ring carbon to another occurs (as shown on the upper line of the figure) in competition with the Diels-Alder process. Calculate the structures and energies of these three monocyclic molecules and of the intramolecular Diels-Alder adducts possible from each of them. For each adduct, be sure to consider the two possible stereoisomers at C* (the newly generated stereogenic center). Comment on the factors responsible for the energy differences among the adducts; decide which of these cyclizations seems feasible.

241. Although benzene, itself, is reluctant to undergo Diels-Alder reactions, strained derivatives (like [2,2]-p-cyclophane, shown to the right) do react with dienophiles like dicyanoacetylene (DCA). Do MMX calculations on the structures and energies of the reactant, of its 1:1 adduct, and of the two possible 1:2 adducts (one corresponding to connection of DCA at carbons a and d, the other at carbons b and c. Only one of these double adducts is formed, something that might be explained based on the MMX calculation. Compare your structures (particularly the degree of non-planarity of the benzene rings) with the x-Ray crystallographic information in the cited reference.

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