Mechanism of the Diels-Alder Reaction

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. 

Concerted TS of the Dtels-Alder Reaction CASSCF/3-21G (CASSCF/6-31G ) 

The behavior described above has been verified by experiment and calculation on numerous substituted dienes and dienophiles. For example Fig. 10.13 shows results for 2°-D isotope effects on Diels-Alder reactions of 2-methyl-butadiene with cyano-ethylene and 1,1-dicyano-ethylene. The calculated and experimental isotope effects are in quantitative agreement with each other and with the results on (butadiene + ethylene). In each case the excellent agreement between calculated and observed isotope effects validates the concerted mechanism and establishes the structure of the transition state as that shown at the bottom center of Fig. 10.11 and the left side of Fig. 10.12a. 

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The mechanism of the Diels-Alder reaction is best understood on the basis of a molecular orbital approach To understand this approach we need to take a more detailed look at the rr orbitals of alkenes and dienes... 

The mechanism of the Diels-Alder reaction is not as simple as usually depicted. This may, in part, explain some of the problems encountered when this reaction has been appHed on an industrial scale. A number of different theories have been proposed for this reaction (50). 

Goldstein, E., Beno, B., Houk, K. N., 1996, Density Functional Theory Prediction of the Relative Energies and Isotope Effects for the Concerted and Stepwise Mechanism of the Diels-Alder Reaction of Butadiene and Ethylene , J. Am. Chem. Soc., 118, 6036. 

The mechanism of the Diels-Alder reaction involves a-overlap of the n-orbitals of two unsaturated systems. One molecule must donate electrons, from its highest occupied molecular orbital (HOMO), to the lowest unoccupied molecular orbital (LUMO) of the other. Also, the two interacting orbitals must have identical symmetry i.e. the phases of the terminal p-orbitals of each molecular orbital must match. There are two possible ways for this to happen the HOMO of the diene combining with the LUMO of the dienophile, and the LUMO of the diene with the HOMO of the dienophile (Figure 7.1). 

When discussing the SC models for the electronic mechanisms of the Diels-Alder reaction between butadiene and ethene [11], and of the disrotatory electrocyclic ringopening of cyclohexadiene, we shall make use of the Rumer spin basis, which allows a straightforward translation of our results into a form that resembles traditional VB ideas. 

In contrast to the great number of calculations concerning the all-carbon Diels-Alder reaction [39], there are only a few theoretical studies on the hetero Diels-Alder reaction [41,42,45 - 53 ]. The general mechanism of the Diels-Alder reaction is still in discussion however, in most cases a concerted reaction is assumed,but there is also evidence for a two-step path. The ab initio calculations carried out for the butadiene/ethene system by Houk, Ortega, Bernardi und Gajewski gave a symmetrical transition structure only using the semiempirical AM1/CI method (half electron approximation) an unsymmetrical diradicaloid intermediate was found [40]. 

The mechanism of the Diels-Alder reaction is a concerted cyclic movement of six electrons four in the diene and two in the dienophile. For the three pairs of electrons to move simultaneously, the transition state must have a geometry that allows overlap of the two end p orbitals of the diene with those of the dienophile. Figure 15-15 shows the required geometry of the transition state. The geometry of the Diels-Alder transition state explains why some isomers react differently from others, and it enables us to predict the stereochemistry of the products. 

Kraka, E. Wu, A. Cremer, D. Mechanism of the Diels-Alder reaction studied with the united reaction vaUey approach mechanistic differences between symmetry-allowed and symmetry-forbidden reactions, 7. Phys. Chem. A 2003,107, 9008-9021. 

Diels-Alder reactions. The SC wavefunction used to describe the electronic mechanism of the Diels-Alder reaction between cis-butadiene and ethene involves six active orbitals which are sufficient to accommodate the four butadiene and two ethene n electrons participating in the bond-breaking and bond-formation... 

Cyclopentadienone is an elusive compound that has been sought for many years but with little success. Molecular orbital calculations predict that it should be highly reactive, and so it is it exists only as the dimer. The tetraphenyl derivative of this compound is to be synthesized in this experiment. This derivative is stable, and reacts readily with dienophiles. It is used not only for the synthesis of highly aromatic, highly arylated compounds, but also for examination of the mechanism of the Diels-Alder reaction itself. Tetraphenylcyclopentadienone has been carefully studied by means of molecular orbital methods in attempts to understand its unusual reactivity, color, and dipole moment. In Chapter 48 this highly reactive molecule is used to trap the fleeting benzyne to form tetraphenylnaphthalene. Indeed, this reaction constitutes evidence that benzyne does exist. 

Here the two molecules have reacted together to give a cyclic adduct. This is the mechanism of the Diels-Alder reaction. Note that the 1,3-butadiene molecule may rotate around the central carbon/carbon bond, but that this rotation is not as easy as it would have been in the case of an isolated carbon/carbon single bond in, say, ethane. Suggest a reason for the slightly restricted nature of the rotation about this central bond in 1,3-butadiene. 

Goldstein E, Beno B, Houk KN. Density functional theory prediction of the relative energies and isotope effects for the concerted and stepwise mechanisms of the Diels-Alder reaction of butadiene and ethylene. J Am Chem Soc 1996 118 6036-6043. 

Mechanism of the Diels-Alder Reaction. Studies of the Addition of Maleic Anhydride to Furan and Methylfurans. 

Although the mechanism of the Diels-Alder reaction is still controversial, it is practically useful to envision a relationship between its transition state (t.s.) and a charge transfer complex. S) In its simplest version, the two enantiomeric t.s. s 6a and 6b become diastereomeric t.s. s if a chiral "solvator" is present Preferential solvation of one of the two enantiotopic... 

Kinetic data on addition reactions, and their implications as to the reaction mechanism, have been reviewed in the recent past this is particularly true for the Diels-Alder reaction - - and its reverse reaction , and for 1,3-cyclo-additions . As well, kinetics and mechanism have been reviewed for particular cases, like Diels-Alder reactions of cyanogen and nitroso derivatives as dienophiles, and of cyclopentadienones as dienes. Other discussions of mechanism, of the Diels-Alder reaction and of 1,2-cycloadditions - , are also worth noting. Another particular case is that of 1,3-cycloadditions of nitrile oxides ", ... 

For a critical discussion of the mechanism of the Diels-Alder reaction, see Sauer, J. Sustmann, R. Angew. Chem. Int. Ed. Engl. 1980,19, 779. 

We will discuss the mechanism of the Diels-Alder reaction in terms of molecular orbitals in Special Topic H in WileyPLUS. For the moment we will continue to describe the Diels-Alder reaction using bonds and curved arrows to describe the movement of electrons that take place. 

The mechanism of the Diels-Alder reaction is discussed further in Special Topic H in WileyPLUS. 

The mechanism of the Diels-Alder reaction was first fully described by Woodward and Hoffmann using their orbital symmetry rules for cycloadditions. The Woodward-Hoffmann rules state that the Diels-Alder reaction is a thermal [4jts + 2 Tis] cycloaddition involving overlap of the diene s highest occupied molecular orbital (HOMO) t / with the dienophile s lowest unoccupied molecular orbital (LUMO) /. In the case of an inverse electron demand Diels-Alder reaction, the dienophile s HOMO / combines with the diene s LUMO... 

The mechanism of the Diels-Alder reaction is now fairly well understood. The accumulated evidence favors a picture in which reorganization of the ir-electrons in the transition state for the reaction occurs so the two new a-bonds are formed in a simultaneous, concerted fashion little charge or free-radical character is developed See more on at any of the terminal carbon atoms (Eq. 12.2). The reaction is one of a number of... 

Mechanism of the Diels-Alder reaction. The diene and dienophile approach each other in parallel planes, one above the other, with the substituents on the dienophile endo to the diene. There is overlap of the orbitals of each molecule and syn addition of each molecule to the other. 

Another serious mechanistic question involves the timing of the formation of the two new o bonds in the cyclohexene. Are they made simultaneously in a concerted fashion, or are they formed in two separate steps In principle, the mechanism of the Diels-Alder reaction could either be concerted or involve two steps (Fig. 12.56). 

To enter the retrosynthesis of TM 2.2a, we need the retrosynthetic tool presented in the following chapters. This is functional group addition (Sect. 1.1.2, Table 1.1). Addition of the C=C bond at the proper position in the cyclohexane ring in TM 2.2a offers an unexpected opportunity. This FGA leads to a cyclohexene derivative amenable to refro-Diels-Alder (refro-D.-A.) disconnection to diene and dienophile. The retrosynthetic step and mechanism of the Diels-Alder reaction are discussed in Example 2.4. 

The mechanism of the Diels-Alder reaction requires that both ends of the diene point in the same direction to be able to reach the dienophile carbons simultaneously. This means that the diene has to adopt the energetically slightly less favorable s-cis conformation, relative to the more stable i-trans form (Figure 14-6). 

The [4-1-2] cycloaddition of dienes to double bonds, the Diels-Alder reaction (see Pericycttc Reactions The Diels-Alder Reaction), is one of the most useful synthetic reactions in organic chemistry. The mechanism of the Diels-Alder reaction has been the subject of intensive study using a large number of different methods. This is at least in part due to the fact that, based on thermochemical estimates, there is a reasonable possibility for a stepwise mechanism. The energy of concert , i.e., the difference between the concerted and a diradicaloid mechanism, is small enough to be potentially overcome in some cases. The comparison of the results for the two different pathways suffers, however, from the difficulties of comparing closed-shell specie.s and diradicals within a single-determinant MO approach. Only recently, the use of multireference and DFT methods in combination with experimental kinetic isotope effect studies allow an unequivocal assessment of the reaction mechanism of the Diels-Alder reaction. ... 

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