Cycloaddition reactions frontier orbital interactions

In cycloaddition reactions, frontier orbital analysis considers the interaction of the HOMO of one component and the LUMO of the other. 

Cycloaddition reactions also have important applications for acyclic chalcogen-nitrogen species. Extensive studies have been carried out on the cycloaddition chemistry of [NSa]" which, unlike [NOa]", undergoes quantitative, cycloaddition reactions with unsaturated molecules such as alkenes, alkynes and nitriles (Section 5.3.2). ° The frontier orbital interactions involved in the cycloaddition of [NSa]" and alkynes are illustrated in Fig. 4.13. The HOMO ( Tn) and LUMO ( r ) of the sulfur-nitrogen species are of the correct symmetry to interact with the LUMO (tt ) and HOMO (tt) of a typical alkyne, respectively. Although both... 

In certain cases, multiple frontier orbital interactions must be considered. This is particularly true of cycloaddition reactions, such as the Diels-Alder reaction between 1,3-butadiene and ethene. 

As it happens, the frontier orbital interactions in the Diels-Alder cycloaddition shown above are like those found in the middle drawing, i.e., the upper and lower interactions reinforce and the reaction proceeds. The cycloaddition of two ethene molecules (shown below), however, involves a frontier orbital interaction like the one on the right, so this reaction does not occur. 

Frontier-orbital Interactions for 1,3-Dipolar Cycloaddition Reactions of Nitrones... 

The structural requirements of the mesomeric betaines described in Section III endow these molecules with reactive -electron systems whose orbital symmetries are suitable for participation in a variety of pericyclic reactions. In particular, many betaines undergo 1,3-dipolar cycloaddition reactions giving stable adducts. Since these reactions are moderately exothermic, the transition state can be expected to occur early in the reaction and the magnitude of the frontier orbital interactions, as 1,3-dipole and 1,3-dipolarophile approach, can be expected to influence the energy of the transition state—and therefore the reaction rate and the structure of the product. This is the essence of frontier molecular orbital (EMO) theory, several accounts of which have been published. 16.317 application of the FMO method to the pericyclic reactions of mesomeric betaines has met with considerable success. The following section describes how the reactivity, electroselectivity, and regioselectivity of these molecules have been rationalized. 

The regioselectivity of cycloaddition of -t with conjugated dienes is the opposite of that observed in numerous nonphoto-chemical reactions of these dienes and provides further evidence for the importance of frontier orbital interactions in determining exciplex geometry and product stereochemistry. 

Frontier orbital interactions are stabilizing the transition states of all the 1,3-dipolar cycloadditions. It is for this reason that one-step 1,3-dipolar cycloadditions are generally possible and, aside from some exotic exceptions, one does indeed observe one-step reactions. 

Theoretical analysis of this [4% + 27r]-cycloaddition reaction by consideration of frontier-orbital interactions between the electron-rich olefin (highest occupied molecular orbital, HOMO) and the electron-poor 5-nitropyrimidine (LUMO) has shown that the FMO perturbation theory correctly predicts an exclusive regiospecific addition of the enamine to N-l and C-4 of the pyrimidine ring (86JOC4070). 

The structural requirements of the mesomeric betaines described in Section III endow these molecules with reactive -electron systems whose orbital symmetries are suitable for participation in a variety of pericyclic reactions. In particular, many betaines undergo 1,3-dipolar cycloaddition reactions giving stable adducts. Since these reactions are moderately exothermic, the transition state can be expected to occur early in the reaction and the magnitude of the frontier orbital interactions, as 1,3-dipole and... 

Figure 2 Frontier orbital interactions in the cycloaddition reaction of NS2+ with alkynes...

The high selectivity for the synclinal transition structure in these models may also arise from frontier orbital interactions. Anh and Thanh have suggested that the stereochemical outcome of an aldol reaction may be controlled by the overlap between the frontier molecular orbitals [23aJ. This same cycloaddition-like transition structure was first used by Mulzer to explain the high selectivity observed in... 

Activation of an alkene to enable addition of carbon radicals may be achieved by complexation of the alkene undergoing addition to an electron-deficient species such as a Lewis acid. This strategy has been used extensively in the activation of dienophiles towards cycloadditions, and the reasons for its efficacy in both cycloaddition and radical addition have the same roots. In a Diels-Alder reaction [4] with normal electron demand, the dominant frontier orbital interaction is between the HOMO of the diene and the LUMO of the dienophile. Complexation of a Lewis acid to the dienophile lowers its LUMO and magnifies the important frontier MO interaction. 

The Diels-Alder cycloaddition reaction of dihydropyran with acrolein was performed in the presence of various H-form zeolites such as H-Faujasites, H-p, H-Mordenites which differ both in their shape selective as well as their acidic properties. The activity of the different catalysts was determined and the reaction products were identified. High 3delds in cycloadduct were obtained over dealuminated HY (Si/Al=15) and Hp (Si/Al=25) compared to HM (Si/Al=10). These results were accounted for in terms of acidity, shape selectivity and microporosity vs mesoporosity properties. The activity and the regioselectivity were then discussed in terms of frontier orbital interactions on the basis of MNDO calculations for thermal and catalyzed reactions by complexing the diene and the dienophile with Bronsted and Lewis acidic sites. From these calculations, Bronsted acidic sites appeared to be more efficient than Lewis acidic sites to achieve Diels-Alder reactions. 

The ethylene-butadiene cycloaddition is a good example to illustrate that symmetry allowedness does not necessarily mean that the reaction occurs easily. This reaction has a comparatively high activation energy, 144 kJ/mol [7-7]. A large number of quantum-chemical calculations has been devoted to this reaction with conflicting results (for recent references, see Ref. [7-18]). It seems, however, that the concerted nature of the prototype Diels-Alder reaction is well established. The reason for the relatively high activation energy is that substantial distortion must occur in the reactants before frontier orbital interactions can stabilize the product. 

Since these reactions are inverse electron demand cycloadditions, the relevant frontier orbital interactions are between the LUMO of the diene and the HOMO of the dienophile. The accelerating effect of a Lewis acid can be understood since complexation of the nitroalkene should decrease the HOMO—LUMO gap by lowering the LUMO of the diene. Thus, the peri-selectivity of the reaction is controlled by the complexation of the nitroalkene to the Lewis acid. 

The Woodward-Hoffmann mles for cycloaddition reactions can be explained from frontier orbital interactions, orbital correlation diagram and aromatic transition... 

F. 3.11 Frontier orbital interactions in a 1,3-dipolar cycloaddition reaction... 

Figure 3.1 Frontier orbital interactions of a thermally forbidden [tt s+tt s]-cycloaddition reaction, b photochemically...

A cyclic transition state model, that differs from the Zimmerman-Traxler and the related cyclic models inasmuch as it does not incorporate the metal in a chelate, has been proposed by Mulzer and coworkers [78] It has been developed as a rationale for the observation that, in the aldol addition of the dianion of phenylacetic acid 152, the high ti-selectivity is reached with naked enolate anions (e.g., with the additive 18-crown-6). Thus, it was postulated that the approach of the enolate to the aldehyde is dominated by an interaction of the enolate HOMO and the n orbital of the aldehyde that functions as the LUMO (Scheme 4.31), the phenyl substituents of the enolate (phenyl) and the residue R of the aldehyde being oriented in anti position at the forming carbon bond, so that the steric repulsion in the transition state 153 is minimized. Mulzer s frontier molecular orbital-inspired approach reminds of a 1,3-dipolar cycloaddition. However, the corresponding cycloadduct 154 does not form, because of the weakness of the oxygen-oxygen bond. Instead, the doubly metallated aldol adduct 155 results. Anh and coworkers also emphasized the frontier orbital interactions as being essential for the stereochemical outcome of the aldol reaction [79]. 

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. 

How can we predict whether a given cycloaddition reaction will occur with suprafacial or with antarafacial geometry According to frontier orbital theory, a cycloaddition reaction takes place when a bonding interaction occurs between the HOMO of one reactant and the LUMO of the other. An intuitive explanation of this rule is to imagine that one reactant donates electrons to the other. As with elec-trocyclic reactions, it s the electrons in the HOMO of the first reactant that are least tightly held and most likely to be donated. But when the second reactant accepts those electrons, they must go into a vacant, unoccupied orbital—the LUMO. 

---