Cycloaddition reactions HOMO-LUMO interactions

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. 

Benzyne shares a feature with A in the [2+2] cycloaddition reactions. The HOMO-LUMO interaction prefers the three-centered interaction (Scheme 4) [115]. This is in agreement with the calculated reaction path [116]. 

Cycloaddition reactions using tropone or another cyclic triene as the 6ji partner have been abundantly described in the literature. It has been found that virtually all metal-free [6 + 4] cycloadditions of cyclic trienes afford predominantly exo adducts. This has been rationalized by consideration of the HOMO-LUMO interactions between the diene and triene partners. An unfavorable repulsive secondary orbital interaction between the remaining lobes of the diene HOMO and those of the triene LUMO develops during an endo approach. The exo transition state is devoid of this interaction (Figure 9). 

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

The 1,3-dipolar cycloaddition of organic azides with nitriles could give rise to two regioisomers. Since organic azides are Type II 1,3-dipoles on the Sustmann classification (approximately equal HOMO-LUMO gaps between the interacting frontier orbital pairs) the reactions could be dipole HOMO or LUMO controled and the regioselectivity should be determined by the orbital coefficients for the dominant HOMO-LUMO interaction. Such systems show U-shaped kinetic curves in their... 

An additional point of interest concerns the behaviour of homo and lumo orbitals of reactants in allowed reactions. Fukui (1970, 1975) has pointed out that the frontier-orbital gap actually narrows as the reaction proceeds. This has been confirmed computationally for the cycloaddition of ethylene and butadiene (Townshend et al., 1976), and contrasts with what one might expect based on a static homo-lumo interaction. Such an interaction causes the energy gap between resultant orbitals to widen, as indicated in Fig. 29. 

Such cycloadditions involve the addition of a 2tt- electron system (alkene) to a 4ir- electron system (ylide) and have been predicted to occur in a concerted manner according to the Woodward-Hoffmann rules. The two most important factors involved in the cycloaddition reactions are (i) the energy and symmetry of the reacting orbitals and (ii) the thermodynamic stability of the cycloadduct. The reactivity of 1,3-dipolar systems has been successfully accounted for in terms of HOMO-LUMO interactions using frontier MO theory (71TL2717). This approach has been extended to explain the 1,3 reactivities of the nonclassical A,B-diheteropentalenes <77HC(30)317). 

The essential features of the Diels-Alder reaction are a four-electron n system and a two-electron it system which interact by a HOMO-LUMO interaction. The Diels-Alder reaction uses a conjugated diene as the four-electron n system and a it bond between two elements as the two-electron component. However, other four-electron it systems could potentially interact widi olefins in a similar fashion to give cycloaddition products. For example, an allyl anion is a four-electron it system whose orbital diagram is shown below. The symmetry of the allyl anion nonbonding HOMO matches that of the olefin LUMO (as does the olefin HOMO and the allyl anion LUMO) thus effective overlap is possible and cycloaddition is allowed. The HOMO-LUMO energy gap determines the rate of reaction, which happens to be relatively slow in this case. 

As with the transition state of the [4+2]-addition of butadiene and ethene (Figure 15.8) both HOMO/LUMO interactions are stabilizing in the transition state of the [2+2]-addition of ketene to ethene (Figure 15.13). This explains why [2+2]-cycloadditions of ketenes to alkenes—and similarly to alkynes—can occur in one-step reactions while this is not so for the additions of alkenes to alkenes (Section 15.2.3). 

Why do the Diels-Alder reactions with both normal and inverse electron demand occur under relatively mild conditions And, in contrast, why can [4+2]-cycloadditions between ethene or acetylene, respectively, and butadiene be realized only under extremely harsh conditions (Figure 15.1) Equation 15.2 described the amount of transition state stabilization of [4+2]-cycloadditions as the result of HOMO/LUMO interactions between the 7T-MOs of the diene and the dienophile. Equation 15.3 is derived from Equation 15.2 and presents a simplified estimate of the magnitude of the stabilization. This equation features a sum of two simple terms, and it highlights the essence better than Equation 15.2. 

Another way to look at this resuft comes from recognizing the special entropy problem involved in cycloaddition reactions. A very precise orientation of the two molecules is required for two bonds to be formed at once. These reactions have large negative entropies of activation (Chapter 41)—order must be created at the transition state as the two components align with one another. The through-space attractive HOMO/LUMO interaction between the two molecules can lead to an initial association that can be compared to a squishy sandwich with... 

We have established earlier in the chapter that there will be favourable Frontier Orbital HOMO-LUMO interactions when two molecules approach for a cycloaddition reaction if there are 4n + 2 electrons involved in a fully suprafacial reaction, or 4n electrons if there is an antarafacial component. For delocalization of electrons in the transition state, the fully suprafacial cycloaddition reaction will result in a continuous cyclic overlap of atomic orbitals in the transition state without a phase change, for which 4n + 2 electrons will give aromatic stabilization. For a cycloaddition with one antarafacial component, the cyclic overlap of orbitals will give a Mobius system for which 4n electrons will provide stabilization. Thus the two approaches, Frontier Orbitals and the Aromatic Transition State will always be in agreement favourable... 

In the remainder of this chapter we will consider further cycloaddition reactions and other examples of pericyclic reactions. We will use the aromatic transition state approach for simplicity, although in all cases an approach based on HOMO-LUMO interactions would give the same result. 

This looks as though each of the C—C bonds is independently the result of both HOMO/LUMO interactions, with an endo selectivity as well. In the presence of dienes, these species behave as allyl cations (see p. 259) and undergo clean [4 + 2] cycloadditions, as in the reaction of the oxyallyl 6.372 giving the tricyclic ketone 6.373, which is similar to the diene 6.369. Normally, oxyallyls are in equilibrium by disrotatory electrocyclic ring closures with cyclopropanones and with allene oxides, but the presence of the five-membered ring in these particular examples makes these pathways counter-thermodynamic. 

Consideration of the HOMO-LUMO interactions also indicates that the [2Tr+2Tr] addition is allowed photochemically. The HOMO in this case is the excited alkene tt orbital. The LUMO is the tt of the ground state alkene, and a bonding interaction is present between both pairs of carbons where new bonds must be formed. Similarly, the concept of aromatic transition states shows that the reaction has an antiaromatic 4tt combination of basis set orbitals, which predicts an allowed photochemical reaction. Thus, orbital symmetry considerations indicate that photochemical [2tt- -2tt] cycloaddition of alkenes is feasible. 

The Diels—Alder reaction may also be analyzed by a similar consideration of the molecular orbitals of butadiene and ethene. In this case, there are two possible HOMO—LUMO interactions. Since the phases of the 1,4-lobes of the HOMO of butadiene match with those in the LUMO of ethene, the [7r" s + TT s] cycloaddition is thermally allowed. We reach a similar conclusion by considering the symmetry of LUMO of butadiene and the HOMO of ethene (Figure 4.10). However, on energetic grounds the latter interaction will make a smaller contribution than the former. 

Since 1,3-DPCA reactions involve Trr-electrons from the 1,3-dipole and 2TT-electrons from the dipolarophiles, it may be considered as symmetry-allowed [tt" s + TT s] cycloaddition resembling Diels—Alder reaction. There is HOMO—LUMO interaction in which either reactant can be the electrophilic or nucleophilic component (Figure 5.12). 

FIGURE 5.19 HOMO—LUMO interactions in cycloaddition reactions involving nitrones. 

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