Orbital Polarization — Substituent Amphoterism

Charge-transfer interactions between frontier molecular orbitals are clearly not the only factors which determine the relative stabilities of various transition states, in spite of the fact that frontier orbital theory has been remarkably successful in accounting for relative reactivities and regioselectivities in various reactions. For example, frontier molecular orbital theory is based on orbital shapes and energies present in the isolated molecules, and these are expected to change upon the approach of one molecule to another. 

We have carried out model calculations to determine how the approach of one reagent to another will influence polarization of frontier molecular orbitals57. As will 

The positive charge increases the polarization of both the HOMO and LUMO, so that the coefficient at the unsubstituted carbon is much larger than that at the methylated carbon, while the LUMO polarization is increased in the opposite direction. However, the effect of the negative charge is to reverse the polarization to some extent. The HOMO remains polarized in the same direction, but the LUMO polarization is reversed. 

The reason for this is outlined in Fig. 22, which shows in the center of the diagram, the it orbitals of ethylene, and the it donor and acceptor orbitals of a generalized substituent. As shown at the left of the diagram, donor substituents cause polarization like that of propene, since the low-lying orbital causes the tt to mix in 

The results not only indicate that the cyano group can act as a donor in cases of extreme electron-demand (at least where HOMO polarization is concerned), but removes some uncertainty as to the true HOMO polarization in unsymmetrical electron-deficient alkenes56). In fact, as an electrophile approaches such a species, the less substituted terminus gains electron density, and is, therefore, the predicted site of attack by electrophiles. 

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