Krische, 310N Lecture 29: Tu - 04/29/03, Ch. 24
DIELS-ALDER REACTION: Several unimolecular reactions proceed through aromatic transition states, i.e. reactions in which there is the concerted cyclic motion of 3 electron pairs (4n + 2 electrons). The decarboxylation of beta-carboxy/keto-acids and the Cope elimination are examples. The Diels-Alder reaction is the [4+2] cycloaddition of a diene and an alkene to give a cyclohexene product. The Diels-Alder reaction has an aromatic transition states involving the concerted cyclic motion of 3 electron pairs (4n + 2 electrons). Note: Related [2+2] cycloadditions and [4+4] cycloadditions are unfavorable as they would involve anti-aromatic transition states. The Diels-Alder Reaction - The Diene Partner: Dienes must be able to adopt an s-cis conformation to participate in Diels-Alder Cycloadditions. For this reason, cyclic dienes work the best. The best diene partners are usually electron rich. In class, we ranked the ability of several 2-subsituted butadienes to participate in Diels-Alder Cycloadditions. The Diels-Alder Reaction - The Dienophile: The best dienophiles are electron deficient, i.e. an alkene that is conjugated to an electron withdrawing group. Stereochemistry of the Diels-Alder Reaction: The Diels-Alder reaction is a concerted process. Because bond-making and bondbreaking occur simultaneously, the reaction is stereospecific. For example, groups that trans- in the dienophile will be trans in the cyclohexene product. Conversely, groups that cis- in the dienophile will be cis- in the cyclohexene product. Endo- versus Exo-Cycloadducts: The Diels-Alder reaction of cyclic dienes gives rise to endo- and exo- products. In the endocycloadduct, the electron-withdrawing group of the dienophile projects inward toward the alkene of the cyclohexene. In the exo-cycloadduct, the electron-withdrawing group of the dienophile projects outward away from the alkene of the cyclohexene and toward the bridging residue of the bicyclic ring system. Be able to draw stereochemically meaningful depictions of the endoand exo-bicyclic ring systems that derive via Diels-Alder reaction of cyclic dienes. Endo-products are kinetic products, while exo-products are thermodynamic products. See the on-line on handout the Diels-Alder reaction for an explanation. Intramolecular Diels-Alder Reaction: The Diels-Alder reaction can also be conducted intramolecularly to give endo- and exoproducts. Be able to predict the stereochemistry of both endo- and exo products, i.e. be able to draw the products. It might be helpful to use molecular models.
[3.3] Sigmatropic Rearrangements: Upon heating, 1,5-dienes undergo a [3.3]sigmatropic rearrangement. If the diene does not have any substituents, this reaction is invisible (a.k.a. degenerate). However, labeling the diene with deuterium reveals that a change has taken place. This reaction is known as the Cope rearrangement. The energy of activation for the Cope rearrangement is only about 34 Kcal/mol. This is far below the energy required to homolytically cleave a C-C single bond, which is about 85 Kcal/mol. Therefore, the Cope rearrangement does not precede through a radical mechanism. This is confirmed by deuterium labeling studies. The low energy of activation for the Cope rearrangement derives from the stabilization inherent to the aromatic transition state.The Cope Rearrangement is Stereospecific: Like the Diels-Alder reaction and other pericyclic reactions, the Cope rearrangement is stereospecific, i.e. the geometry of the starting material dictates the geometry of the product. T...