Frontier cyclohexanones

For axial and equatorial nucleophilic addition to cyclohexanone, the principle of microscopic reversibility dictates that frontier orbital analysis can be considered for addition of the nucleophile to the carbonyl or loss of nucleophile from the product. Since the reaction is considered to be exothermic the frontier orbital interaction that should best represent the transition energy is the orbital interaction of the nucleophile HOMO with the ketone n (LUMO) (Fig. 6-11). 

Figure 6-11. (top) Frontier molecular orbitals, (bottom) potential energy surface for axial and equator-ial attack at 3-substituted cyclohexanones. 

Figure 6-12. The effect of frontier orbital interactions of proximate C-H and RC-C bonds on A lumo-homo for nucleophilic axial and equatorial attack at cyclohexanones.

The Exterior Frontier Orbital Extension (EFOE) model has been applied to predict r-facial selectivity in nucleophilic additions to imines and iminium ions of the cyclohexanone, tropinone, and adamantan-2-one systems." A review of the EFOE model," and other references to its use, are described later under Regio-, Enantio-, and Diastereo-selective Aldol Reactions. 

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