Frontier MO theory

The [2 + 2] photodimerization of a, j8-unsaturated sulfones is correctly viewed as a photoreaction of alkenes, rather than the sulfone group, and this aspect has been reviewed recently by Reid, as part of a wider survey of the photoreaction of O- and S-heterocycles. The topic continues to attract considerable interest and a few recent examples, as well as some synthetic applications, will be discussed here. Much of the photodimerization work has been carried out on the benzo[fc]thiophene (thianaphthene) 1,1-dioxide system. For example. Porter and coworkers have shown that both 3-carboxybenzo[i]thiophene 1,1-dioxide (65) and its methyl ester give only the head-to-head (hth), anti dimer (66) on irradiation in ethanol. In a rather unusual finding for such systems, the same dimer was obtained on thermal dimerization of 65. Similar findings for a much wider variety of 3-substituted benzo[fi]thiophene 1,1-dioxides have been reported more recently by Geneste and coworkers . In the 2-substituted analogs, the hth dimer is accompanied by some of the head-to-tail (htt), anti dimer. The formation of the major dimer appears to proceed by way of an excited triplet and the regiochemistry observed is in accord with frontier MO theory. 

This quantity can be viewed as a generalization of Fukui s frontier molecular orbital (MO) concept [25] and plays a key role in linking Frontier MO theory and the HSAB principle. It can be interpreted either as the sensitivity of a system s chemical potential to an external perturbation at a particular point r, or as the change of the electron density p(r) at each point r when the total number of electrons is changed. The former definition has recently been implemented to evaluate this function [26,27] but the derivative of the density with respect to the number of electrons remains by far the most widely used definition. 

Such cycloadditions involve the addition of a 2tt- electron system (alkene) to a 4ir- electron system (ylide) and have been predicted to occur in a concerted manner according to the Woodward-Hoffmann rules. The two most important factors involved in the cycloaddition reactions are (i) the energy and symmetry of the reacting orbitals and (ii) the thermodynamic stability of the cycloadduct. The reactivity of 1,3-dipolar systems has been successfully accounted for in terms of HOMO-LUMO interactions using frontier MO theory (71TL2717). This approach has been extended to explain the 1,3 reactivities of the nonclassical A,B-diheteropentalenes <77HC(30)317). 

The primary adducts (156) and (157) of oxazoles with alkenes and alkynes, respectively, are usually too unstable to be isolated. An exception is compound (158), obtained from 5-ethoxy-4-methyloxazole and 4,7-dihydro-l,3-dioxepin, which has been separated into its endo and exo components. If the dienophile is unsymmetrical the cycloaddition can take place in two senses. This is usually the case in the reactions of oxazoles with monosubstituted alkynes with alkenes on the other hand, regioselectivity is observed. Attempts to rationalize the orientation of the major adducts by the use of various MO indices, such as 7r-electron densities or localization energies and by Frontier MO theory (80KGS1255) have not been uniformly successful. A general rule for the reactions of alkyl- and alkoxy-substituted oxazoles is that in the adducts the more electronegative substituent R4 of the dienophile occupies the position shown in formula (156). The primary adducts undergo a spontaneous decomposition, whose outcome depends on the nature of the groups R and on whether alkenes or alkynes have been employed. 

Frontier MO theory can be used to understand the dependence of the rate of the Diels-Alder reaction on the electronic nature of the substrates. As in any reaction, the rate of the Diels-Alder reaction is determined by the energy of its TS. In the TS of most Diels-Alder reactions, the HOMO of the diene interacts with the LUMO of the dienophile. 

Some cycloadditions proceed thermally, whereas others require hv. The dependence of certain cycloadditions on the presence of light can be explained by examining interactions between the MOs of the two reacting components. Frontier MO theory suggests that the rate of cycloadditions is determined by the strength of the interaction of the HOMO of one component with the LUMO of the other. In normal electron-demand Diels-Alder reactions, HOMOdiene ( Ai) interacts with LUMOdienophiie (< >i ) There is positive overlap between the orbitals where the two cr bonds form when both components of the reaction react from the same face of the tt system (suprafacially). 

The regiochemistry of the addition of 54 to isoprene and trans-piperylene is that expected from frontier MO theory, with the methyl substituent on the diene located metd to the silicon atom305. The selectivity is higher in the case of trans-piperylene. 

Besides the above proof, Li and Evans have demonstrated the HSAB principle through the local descriptors and softness kernel in their proof. One of the impressive features of their study is that the Fukui function is shown to be one of the key concepts in relating the frontier MO theory and the HSAB principle. The final expression for the interaction energy, considering the interaction between two molecules i and j, takes the form... 

The cycloaddition of ketones with nitrile ylides proceeds much more slowly than the corresponding cycloaddition with aldehydes. On the other hand, ketones with electron-withdrawing groups such as trifluoromethyl, ethoxycar-bonyl, nitrile, or phosphonate at the a position react rapidly with the 1,3 dipole. All of this is understandable in terms of frontier MO theory. Nitrile... 

In contrast to the o-allylphenyl substituted 2/f-azirines (197 and 200) which undergo 1,1 cycloaddition, azirine 203 cycloadds exclusively in the 1,3 sense. The formation of the 1,3-dipolar cycloadduct 204 is quite consistent with the principles of frontier MO theory. With this system the rate of internal 1,3-dipolar cycloaddition of the nitrile ylide derived from 203 proceeds much more rapidly than that of the ylides derived from 197 and 200. This is to be expected since electron-withdrawing substituents on the double bond narrow the HO dipole-LU dipolarophile gap. In order for the 1,3-dipolar cycloaddition of 209 to occur, a slight distortion away from the strictly parallel-plane approach of the dipole and dipolarophile will be necessary. The interplay of entropy and... 

Now let us turn to the case of a highly reactive electrophile, where we expect an early transition state. In this case the total charge density and the coefficient of the HOMO at each atom would be expected to be the features governing the orientation of electrophilic attack. The transition state should resemble the reactants and, according to frontier MO theory, the electrophile should attack the positions with the largest coefficients for the HOMO. The case of anisole can be taken as a... 

Table 5 Correlation of the ionization potential of olefins with the selectivity of the addition and with frontier MO theory...

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