Diels-Alder reaction diradical mechanism

There are, broadly speaking, three possible mechanisms that have been considered for the uncatalyzed Diels-Alder reaction. In mechanism a there is a cyclic six-centered transition state and no intermediate. The reaction is concerted and occurs in one step. In mechanism b, one end of the diene fastens to one end of the dienophile first to give a diradical, and then, in a second step, the other ends become fastened. A diradical formed in this manner must be a singlet that is, the... 

For most Diels-Alder reactions a concerted mechanism as described above, is generally accepted. In some cases, the kinetic data may suggest the intermediacy of a diradical intermediate 18 ... 

It must be emphasized once again that the rules apply only to cycloaddition reactions that take place by cyclic mechanisms, that is, where two s bonds are formed (or broken) at about the same time. The rule does not apply to cases where one bond is clearly formed (or broken) before the other. It must further be emphasized that the fact that the thermal Diels-Alder reaction (mechanism a) is allowed by the principle of conservation of orbital symmetry does not constitute proof that any given Diels-Alder reaction proceeds by this mechanism. The principle merely says the mechanism is allowed, not that it must go by this pathway. However, the principle does say that thermal 2 + 2 cycloadditions in which the molecules assume a face-to-face geometry cannot take place by a cyclic mechanism because their activation energies would be too high (however, see below). As we shall see (15-49), such reactions largely occur by two-step mechanisms. Similarly. 2 + 4 photochemical cycloadditions are also known, but the fact that they are not stereospecific indicates that they also take place by the two-step diradical mechanism (mechanism... 

The observation that the transition state volumes in many Diels-Alder reactions are product-like, has been regarded as an indication of a concerted mechanism. In order to test this hypothesis and to gain further insight into the often more complex mechanism of Diels-Alder reactions, the effect of pressure on competing [4 + 2] and [2 + 2] or [4 + 4] cycloadditions has been investigated. In competitive reactions the difference between the activation volumes, and hence the transition state volumes, is derived directly from the pressure dependence of the product ratio, [4 + 2]/[2 + 2]p = [4 + 2]/[2 + 2]p=i exp —< AF (p — 1)/RT. All [2 + 2] or [4 + 4] cycloadditions listed in Tables 3 and 4 doubtlessly occur in two steps via diradical intermediates and can therefore be used as internal standards of activation volumes expected for stepwise processes. Thus, a relatively simple measurement of the pressure dependence of the product ratio can give important information about the mechanism of Diels-Alder reactions. 

These experimental secondary deuterium KIEs observed in Diels-Alder reactions have been compared with the respective theoretical KIEs for the stepwise mechanism involving a diradical intermediate (equation 88a) and for concerted synchronous and asynchronous mechanisms (equation 88b) for the Diels-Alder reaction of butadiene with ethylene207. 

The Diels-Alder reaction is the best known and most widely used pericyclic reaction. Two limiting mechanisms are possible (see Fig. 10.11) and have been vigorously debated. In the first, the addition takes place in concerted fashion with two equivalent new bonds forming in the transition state (bottom center, Fig. 10.11), while for the second reaction path the addition occurs stepwise (top row, Fig. 10.11). The stepwise path involves the formation of a single bond between the diene (butadiene in our example) and the dienophile (ethylene) and (most likely) a diradical intermediate, although zwitterion structures have also been proposed. In the last step, ring closure results with the formation of a second new carbon carbon bond. Either step may be rate determining. 

Fig. 10.11 The stepwise and concerted mechanisms for the Diels-Alder reaction between butadiene and ethylene. The reactants (lower left) proceed to the product, cyclohexene (lower right) either through a two step, two transition state mechanism involving the formation of a diradical intermediate (top center), or more directly through the symmetric synchronous transition state (bottom center) (Storer, J. W., Raimondi, L., and Houk, K. N., J. Am. Chem. Soc. 116, 9675 (1994))...

A semiempirical AMI study of the inverse-electron-demand Diels-Alder reaction of 4-substituted 6-nitrobenzofurans with enol ethers and enamines favours a stepwise mechanism involving short-lived diradical intermediates. The inverse-electron-demand intermolecular Diels-Alder reactions of 3,6-bis(trifluoromethyl)-l,2,4,5-tetra-zine with acyclic and cyclic dienophiles followed by the elimination of N2 produce 4,5-dihydropyridazines, which cycloadd further to yield cage compounds. The preparation of jS-carbolines (90) via an intramolecular inverse-electron-demand Diels-Alder... 

The reaction is similar to the Diels-Alder (in action, not in scope), and if dienes are involved, the latter reaction may compete, though most olefins react with a diene either entirely by 1,2 or entirely by 1,4 addition. Three mechanisms can be proposed938 analogous to those proposed for the Diels-Alder reaction. Mechanism a is a concerted pericyclic process, and mechanisms b and c are two-step reactions involving, respectively, a diradical (99) and a diion (100) intermediate. As in 5-47, a diradical intermediate must be a singlet. 

The rates of Diels-Alder reactions are little affected by the polarity of the solvent. If a zwitterionic intermediate were involved, the intermediate would be more polar than either of the starting materials, and polar solvents would solvate it more thoroughly. Typically, a large change of solvent dipole moment, from 2.3 to 39, causes an increase in rate by a factor of only 10. In contrast, stepwise ionic cycloadditions take place with increases in rate of several orders of magnitude in polar solvents. This single piece of evidence rules out stepwise ionic pathways for most Diels-Alder reactions, and the only stepwise mechanism left is that involving a diradical. 

Various reaction mechanisms are known for ene reactions. Both single-step synchronous reaction and stepwise processes involving diradicals or zwitterionic transition states have been discussed. One of the three bonds broken in the course of the reaction is a a bond, which dictates a high activation energy relative to a Diels-Alder reaction (see Chapter 2). For this reason if the reaction is conducted thermally, temperatures above 100 C are required. However, the reactivity of the enophile can be increased by addition of a Lewis acid, permitting milder reaction conditions. The Lewis acid coordi-... 

The Diels-Alder reaction and related pericyclic reactions, which can be treated qualitatively by the Woodward-Hoffmann rules (Section 4.3.5), have been reviewed in the context of computational chemistry [39]. The reaction is clearly nonionic, and the main controversy was whether it proceeds in a concerted fashion as indicated in Fig. 9.5 or through a diradical, in which one bond has formed and two unpaired electrons have yet to form the other bond. A subtler question was whether the reaction, if concerted, was synchronous or asynchronous whether both new bonds were formed to the same extent as reaction proceeded, or whether the formation of one ran ahead of the formation of the other. Using the CASSCF method (Section 5.4.3), Li and Houk [40] concluded that the butadiene-ethene reaction is concerted and synchronous, and chided Dewar and Jie [41] for stubbornly adhering to the diradical (biradical) mechanism. 

The most likely multistep mechanism of this type is shown in the lower part of Figure 12.17. It is a two-step mechanism where the diastereomeric diradicals F and G are the two intermediates that allow for rotation about the configuration-determining C—C bond. Each of the two radical centers is part of a well-stabilized allyl radical (cf. Section 1.2.1). It is unknown whether the formation of biradical F is subject to simple diastereoselectivity in comparison to G (for the occurrence of simple diastereoselec-tivity in one-step Diels-Alder reactions, see Section 12.3.4). Biradicals F and G cyclize without diastereocontrol to deliver the [4+2]-cycloadducts biradical F forms a mixture of1 2trans,cis-[D]2-C and 1,2trans, trans [D]2-C, since a rotation about the C2—C3 bond is possible but not necessary. For the same reason, biradical G forms a mixture of 1 2cis,cis- I) 2-C and 1,2cis,trans [D]2-C. 

An alternative mechanism for the Diels-Alder reaction involves a stepwise pathway (Reaction 4.3). Here, one end of the butadiene and ethylene fragments approach each other, passing through transition state 6, to form a diradical intermediate 7. In a second distinct chemical step, the second new o-bond is formed through transition state 8 to give cyclohexene. 

Alder reaction the major Diels-Alder product is the trans adduct rather than the cis adduct (Scheme 11). Such a stereochemistry indicates that the Diels-Alder reactions proceed by a stepwise mechanism rather than a concerted mechanism. The photo-induced electron transfer from Danishefsky s diene to Ceo gives the triplet radical ion pair. The triplet radical ion pair is then converted to the singlet radical ion pair to give a zwitterionic intermediate (or a diradical intermediate) in competition with the back electron transfer to the reactant pair. The bond formation occurs stepwise with no symmetry restriction for the bond formation. Thus, both trans and cis adducts were obtained as the final products [305]. 

Orlova, G., Goddard, J. D. Competition between Diradical Stepwise and Concerted Mechanisms in Chalcogeno-Diels-Alder Reactions A Density Functional Study. J. Org. Chem. 2001, 66, 4026-4035. 

Consider whether formation of ionic rather than diradical intermediates would affect the argument in favor of a two-step mechanism for the Diels-Alder reaction. What information does the fact that typical Diels-Alder additions occur in the vapor state give about free-radical vs. ionic reaction mechanisms ... 

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