Diels-Alder reaction HOMO-LUMO interactions

The purely inductive electron-withdrawing character of a fluoroalkyl substituent activates alkenes in Diels-Alder reactions via the interaction of the HOMO of the diene and the LUMO of the fluoroalkyl-containing alkene. 

Some cycloadditions proceed thermally, whereas others require hv. The dependence of certain cycloadditions on the presence of light can be explained by examining interactions between the MOs of the two reacting components. Frontier MO theory suggests that the rate of cycloadditions is determined by the strength of the interaction of the HOMO of one component with the LUMO of the other. In normal electron-demand Diels-Alder reactions, HOMOdiene ( Ai) interacts with LUMOdienophiie (< >i ) There is positive overlap between the orbitals where the two cr bonds form when both components of the reaction react from the same face of the tt system (suprafacially). 

The same conclusions are drawn by analysis of the frontier orbitals involved in cycloadditions. For the most common case of the Diels-Alder reaction, which involves dienophiles with electron-attracting substituents, the frontier orbitals are l/2 of the diene (which is the HOMO) and n of the dienophile (which is the LUMO). Reaction occurs by interaction of the HOMO and LUMO, which can be seen from the illustration below to be allowed. 

When both the 1,3-dipoIe and the dipolarophile are unsymmetrical, there are two possible orientations for addition. Both steric and electronic factors play a role in determining the regioselectivity of the addition. The most generally satisfactory interpretation of the regiochemistry of dipolar cycloadditions is based on frontier orbital concepts. As with the Diels-Alder reaction, the most favorable orientation is that which involves complementary interaction between the frontier orbitals of the 1,3-dipole and the dipolarophile. Although most dipolar cycloadditions are of the type in which the LUMO of the dipolarophile interacts with the HOMO of the 1,3-dipole, there are a significant number of systems in which the relationship is reversed. There are also some in which the two possible HOMO-LUMO interactions are of comparable magnitude. 

According to Frontier Molecular Orbital (FMO) theory, Diels-Alder reaction between an electron-rich diene and an electron-poor dienophile involves interaction between the highest-occupied molecular orbital (HOMO) on the diene and the lowest-unoccupied molecular orbital (LUMO) on the dienophile. The better the HOMO/LUMO overlap and the smaller their energy difference, the more favorable the interaction and the faster the reaction. 

The FMOs of acrolein to the left in Fig. 8.2 are basically slightly perturbed butadiene orbitals, while the FMOs of protonated acrolein resemble those of an allyl cation mixed in with a lone-pair orbital on the oxygen atom (Fig. 8.2, right). Based on the FMOs of protonated acrolein, Houk et al. [2] argued that the predominant interaction in a normal electron-demand carbo-Diels-Alder reaction is between the dienophile LUMO and diene HOMO (Fig. 8.1, left). This interaction is greatly... 

The basic concept of activation in hetero-Diels-Alder reactions is to utilize the lone-pair electrons of the carbonyl and imine functionality for coordination to the Lewis acid. The coordination of the dienophile to the Lewis acid changes the FMOs of the dienophile and for the normal electron-demand reactions a decrease of the LUMO and HOMO energies is observed leading to a better interaction with... 

Fora [4 + 2 -7r-electron cycloaddition (Diels-Aldei reaction), let s arbitrarily select the diene LUMO and the alkene HOMO. The symmetries of the two ground-slate orbitals are such that bonding of the terminal lobes can occur with suprafacial geometry (Figure 30.9), so the Diels-Alder reaction takes place readily under thermal conditions. Note that, as with electrocyclic reactions, we need be concerned only with the terminal lobes. For purposes of prediction, interactions among the interior lobes need not be considered. 

Figure 30.9 Interaction of diene LUMO and alkene HOMO in a suprafacial 14 - 2] cycloaddition reaction (Diels-Alder reaction).

According to frontier molecular orbital theory (FMO), the reactivity, regio-chemistry and stereochemistry of the Diels-Alder reaction are controlled by the suprafacial in phase interaction of the highest occupied molecular orbital (HOMO) of one component and the lowest unoccupied molecular orbital (LUMO) of the other. [17e, 41-43, 64] These orbitals are the closest in energy Scheme 1.14 illustrates the two dominant orbital interactions of a symmetry-allowed Diels-Alder cycloaddition. 

In a photochemical cycloaddition, one component is electronically excited as a consequence of the promotion of one electron from the HOMO to the LUMO. The HOMO -LUMO of the component in the excited state interact with the HOMO-LUMO orbitals of the other component in the ground state. These interactions are bonding in [2+2] cycloadditions, giving an intermediate called exciplex, but are antibonding at one end in the [,i4j + 2j] Diels-Alder reaction (Scheme 1.17) therefore this type of cycloaddition cannot be concerted and any stereospecificity can be lost. According to the Woodward-Hoffmann rules [65], a concerted Diels-Alder reaction is thermally allowed but photochemically forbidden. 

The chemical reactions through cyclic transition states are controlled by the symmetry of the frontier orbitals [11]. At the symmetrical (Cs) six-membered ring transition state of Diels-Alder reaction between butadiene and ethylene, the HOMO of butadiene and the LUMO of ethylene (Scheme 18) are antisymmetric with respect to the reflection in the mirror plane (Scheme 24). The symmetry allows the frontier orbitals to have the same signs of the overlap integrals between the p-or-bital components at both reaction sites. The simultaneous interactions at the both sites promotes the frontier orbital interaction more than the interaction at one site of an acyclic transition state. This is also the case with interaction between the HOMO of ethylene and the LUMO of butadiene. The Diels-Alder reactions occur through the cyclic transition states in a concerted and stereospecific manner with retention of configuration of the reactants. 

Diels-Alder cycloadditions involving norbomene 57 [34], benzonorbomene (83), 7-isopropylidenenorbomadiene and 7-isopropylidenebenzonorbomadiene (84) as dienophiles are characterized as inverse-electron-demand Diels-Alder reactions [161,162], These compounds react with electron-deficient dienes, such as tropone. In the inverse-electron-demand Diels-Alder reaction, orbital interaction between the HOMO of the dienophile and the LUMO of the diene is important. Thus, orbital unsymmetrization of the olefin it orbital of norbomene (57) is assumed to be involved in these top selectivities in the Diels-Alder cycloaddition. 

In the case of the reverse-electron-demand Diels-Alder reactions, the secondary orbital interaction between the Jt-HOMO of dienophile and the LUMO of 114 or the effect of the orbital phase enviromnents (Chapter Orbital Phase Enviromnents and Stereoselectivities by Ohwada in this volume) cannot be ruled out as the factor controlling the selectivity (Scheme 55). 

Fig. 6.1. Interaction between LUMO of dienophile and HOMO of diene in the Diels-Alder reaction.

Fig. 6.2. HOMO-LUMO interactions rationalize regioselectivity of Diels-Alder reactions.

Despite the fact that the exo adduct is likely to be the more stable of the two thermodynamically, it is often (though not universally) found in Diels-Alder reactions that the endo adduct is the major, if not the sole, product. To explain this, it has been suggested that in endo addition stabilisation of the T.S. can occur (and the rate of reaction thereby speeds up) through secondary interaction of those lobes of the HOMO in, e.g. (32) and of the LUMO in (33) that are not themselves involved directly in bond-formation, provided these are of the same phase. Such interaction would not, of course, be possible in the T.S. for exo addition because the relevant sets of centres in (32) and (33) will now be too far apart from each other the endo adduct is thus the kinetically controlled product. It is significant in this connection that the relative proportion of exo... 

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). 

The main stabilization in reactions with activated reaction partners, viz. when one partner is electron-rich and the other electron-poor, arises through interaction between the donor HOMO and the acceptor LUMO which are much closer in energy than the acceptor HOMO and the donor LUMO. Figure 2 illustrates which interactions between the frontier orbitals cause the main stabilization in normal, neutral and inverse Diels-Alder reactions. For example, the main stabilization in the reaction between an electron-rich diene and an electron-poor dienophile stems from the interaction of the diene HOMO with the dienophile LUMO. 

The endo selectivity in many Diels-Alder reactions has been attributed to attractive secondary orbital interactions. In addition to the primary stabilizing HOMO-LUMO interactions, additional stabilizing interactions between the remaining parts of the diene and the dienophile are possible in the endo transition state (Figure 3). This secondary orbital interaction was originally proposed for substituents having jr orbitals, e.g. CN and CHO, but was later extended to substituents with tt(CH2) type of orbitals, as encountered in cyclopropene57. 

The interactions of the occupied orbitals of one reactant with the unoccupied orbitals of the other are described by the third term of the Klopman-Salem-Fukui equation. This part is dominant and the most important for uncharged reaction partners. Taking into account that the denominator is minimized in case of a small energy gap between the interacting orbitals, it is clear that the most important interaction is the HOMO-LUMO overlap. With respect to the Diels-Alder reaction, one has to distinguish between two possibilities depending on which HOMO-LUMO pair is under consideration. The reaction can be controlled by the interaction of the HOMO of the electron-rich diene and the LUMO of the electron-poor dienophile (normal electron demand) or by the interaction of the LUMO of an electron-poor diene and the HOMO of an electron-rich dienophile (inverse electron demand cf Figure 1). 

FIGURE 1. The HOMO/LUMO interactions in Diels-Alder reactions with normal and inverse electron demand... 

Lewis acid catalysis enormously enriches the scope of Diels-Alder reactions, but it is limited to reagents containing Lewis basic sites, i.e. functional groups with lone pairs such as carbonyl, amino, ether or nitro close to the reaction centre. As we have seen in the discussion about the FMO aspects of Lewis acids, the major reason for catalysis is the reduction of the HOMO-LUMO gap. In case of Diels-Alder reactions with normal electron demand, it follows that the coordination of the Lewis acid lowers the LUMO energy of the dienophile. Such interactions are only possible if there is a spatial proximity or an electronic conjugation between the coordinated Lewis basic site and the reaction centre. Fortunately, in nearly every Diels-Alder reaction one of the reagents, mostly the dienophile, meets this requirement. 

These results led to a separation of the observed Diels-Alder reactivities into three categories (a) increase of the rate constants on increasing the Lewis acid character of the solvent as quantified by the AN parameter this behaviour reflects the interactions between the LUMO of the solvent and the HOMO of the reactants and is similar to Lewis acid catalysis (vide supra) (b) reaction retardation by electron donation, as quantified by the D-ji parameter the HOMOsoivent-LUMOreactant interactions are held responsible for this effect, representing an anti-Lewis acid interaction which increases the HOMO-LUMO gap and hence hampers the reaction (c) the Diels-Alder reactions show very small solvent effects and are relatively insensitive to specific reactant-solvent interactions, and... 

The Diels-Alder reaction is the reaction of a diene with a mono-ene to form a cyclohexene derivative, an important reaction for the construction of organic intermediates. One of its attractions is the atom efficiency of 100%, no by-products being formed. The mono-ene, or dienophile which may also be an alkync, has a LUMO of low energy while the diene is usually electron rich with a high lying HOMO. The interaction of these two orbitals starts the reaction between the two molecules (Figure 2.33) [26],... 

Problem 9.33 When applying the Woodward-Hoffmann rules to the Diels-Alder reaction, (a) would the same conclusion be drawn if the LUMO of the dienophile interacts with the HOMO of the diene (b) Would the reaction be light-catalyzed ... 

Orbital Interaction Analysis. An orbital interaction diagram for the Diels-Alder reaction is shown in Figure 12.5a. The geometry of approach of the two reagents which ensures a maximum favorable interaction between the frontier MOs (dashed lines) preserves a plane of symmetry at all separations. The MOs are labeled according to whether they are symmetric (S) or antisymmetric (A) with respect to reflection in the plane. Simultaneous overlap of both HOMO-LUMO pairs is a necessary feature of all peri-... 

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