Frontier interactions

To recap splitting a molecule into fragments (Section 2.4) allows unimolecu-lar reactions to be treated as bimolecular processes. Only one or two frontier interactions have to be considered, irrespective of the problem (Section 2.3). Two cases can be distinguished ... 

Moreover, it can be shown5 that the frontier coefficients increase at the reaction centers, thus enforcing the role of frontier interactions. 

Frontier orbital theory must always be used with the utmost caution in structural problems, for two reasons. The first, and main reason, is that frontier interactions are only dominant in the transition state and in structural problems the structures under study are stable ones. Furthermore, if a transition state may be considered with good reasons to be the perturbed initial system, as the bonds undergoing transformation are not completely formed or completely broken, this is no longer true in structural problems. The formal recombination of two fragments to give the final product corresponds to the complete formation of one or several new bonds, an important modification which may not always be treated as a perturbation. That is the second reason. 

The addition of a carbene to a double bond is easily dealt with by FO theory only the non-linear approach allows a good frontier interaction (Figure 4.9). This result is in agreement with the selection rules quoted earlier the system having four electrons (two coming from the carbene and two from the ethylene) and its n component... 

Figure 4.9 Frontier interactions between a carbene and a double bond.

Rule 3 Reaction occurs preferentially at the site having the highest frontier interaction with the incoming reagent. 

Figure 6.2 Major frontier interactions for an electron-donating substituent. Wavy line = unfavorable interaction dotted line = favorable interaction.

This FO treatment has been criticized by Inagaki et al.,35 who pointed out that the acetoxycyclopentadiene HOMO should be antibonding between the lone pair and the ring n system so that when the secondary interaction between the oxygen and the dienophile is favorable, the main diene-dienophile frontier interaction is unfavorable (wavy lines in the diagram below) ... 

Note that a frontier interaction such as HOMO(l)-LUMO(2) automatically implies electron transfer from molecule (1) to molecule (2), so that electrostatic factors are already partially taken into account in frontier control. 

Care must be taken in generalizing gas-phase computational results, which tend to overemphasize charge control while underemphasizing frontier control. Indeed, in the absence of solvent, coulombic forces, which vary as the inverse square of the distance, are stronger at large distances than frontier interactions, which diminish exponentially with the separation. The reaction then becomes charge controlled with an early transition state in which the reagents may still be in their most stable conformations. The role of the conformational effect is then somewhat overstated. This is especially true in older calculations in which O or Cl were replaced by F and Na+ and K+ were modeled by Li+. 

In mesityl oxide, the two new methyls increase the frontier interactions which favor the transoid form, but this cannot compensate for the strong steric repulsion between Q and the methyl located at C4 ... 

Semi-empirical models, like force field methods, perform best when their parameters are good, that is, for well-known systems. They cannot predict completely new structures. Even for known compounds, their results are not always dependable. Thus, semi-empirical calculations tend to overstress diradical mechanisms in cycloadditions.17 AMI and PM3 underestimate frontier interactions with respect to steric repulsions. Basicities of anions are overestimated and their nucleophilicities underestimated. Optimizations may give unreasonable structures. Usually, but not systematically, PM3 gives more reliable structures and AMI more realistic energies.18... 

Scheme 3 Orbital frontier interactions foj- thermal and catalyzed reaction...

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