Frontier orbitals, imine

The reaction mechanism proposed for the LiBr/NEta induced azomethine ylide cycloadditions to a,p-unsaturated carbonyl acceptors is illustrated in Scheme 11.10. The ( , )-ylides, reversibly generated from the imine esters, interact with acceptors under frontier orbital control, and the lithium atom of ylides coordinates with the carbonyl oxygen of the acceptors. Either through a direct cycloaddition (path a) or a sequence of Michael addition-intramolecular cyclization (path b), the cycloadducts are produced with endo- and regioselectivity. Path b is more likely, since in some cases Michael adducts are isolated. 

The reaction of the acid chloride phenylhydrazone (11) with base gives the nitrile-imine 1,3-dipolar compound (12) which reacts with potassium thiocyanate to give the A2-thiadiazo-line (13 Scheme 1). Thus the cycloaddition occurs at the C=S and not the C=N bond. This regioselectivity can be explained in terms of the frontier orbital treatment. Due to the electron rich nature of the thiocyanate anion, its reaction with (12) is expected to be controlled by the LUMO and HOMO of (12) and the thiocyanate respectively. As the HOMO of the thiocyanate anion has the larger orbital coefficient on the sulfur atom, it can be concluded that the larger orbital coefficient in the LUMO of (12) is on the carbon atom. This is also in agreement with other dipolar cycloadditions (82H( 19)57). 

Dipolarophiles with electronegative heteroatoms such as carbonyl groups, imines and cyano groups also show an orientation in agreement with frontier orbital theory. Because heterodienophiles all have low-energy LUMOs, their reactions will usually be dipole-HO-controlled. The reaction of diazomethane with an imine giving the triazoline 6.240 and the final step in the formation of an ozonide... 

Fig. 6.46 Frontier orbitals for azomethine imines and representative dipolarophiles...

In closing, it is pointed out that the ionization patterns of nitrile imines (Figure 8) confirm the proposed frontier orbital sequence, which allows their regioselectivity to be rationalized in 1,3-dipolar additions79. 

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. 

---