1.3- dipoles frontier orbitals

When both the 1,3-dipoIe and the dipolarophile are unsymmetrical, there are two possible orientations for addition. Both steric and electronic factors play a role in determining the regioselectivity of the addition. The most generally satisfactory interpretation of the regiochemistry of dipolar cycloadditions is based on frontier orbital concepts. As with the Diels-Alder reaction, the most favorable orientation is that which involves complementary interaction between the frontier orbitals of the 1,3-dipole and the dipolarophile. Although most dipolar cycloadditions are of the type in which the LUMO of the dipolarophile interacts with the HOMO of the 1,3-dipole, there are a significant number of systems in which the relationship is reversed. There are also some in which the two possible HOMO-LUMO interactions are of comparable magnitude. 

The type of conjugation is also reflected in the frontier orbital profile, the charge distribution, and the permanent dipole moments. The results of semiempirical calculations on l-methylpyridinium-3-olate (16), Malloapeltine (17), Trigollenine (18), and Homarine (19) are presented in Scheme 7. Characteristically for the class of conjugated mesomeric betaines, the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) are distributed over the entire molecule as examplifled for l-methylpyridinium-3-olate. It was shown that 90% of the... 

Predictions obtained by using the frontier orbital approximation213 were unsuccessful, apparently due to inadequacies in these MO calculations mostly involving the energy gap between HO of the dipole and LU of the dipolarophile. 

Electron affinities for 35 substituted nitrobenzenes have been reported and provided a comprehensive data set for the examination of substituent effects38. The data were used to derive Taft gas-phase substituent parameters and discussed qualitatively based on frontier orbital molecular theory38. The rate constants for the exo-energetic electron-transfer reactions were found to be close to those predicted by the ADO (average dipole orientation) theory38. 

We now turn to the gas-phase 1,3-dipolar cycloaddition of fulminic acid to ethyne. The concerted, almost synchronous nature of this reaction might create the impression that the electronic mechanism of this process should be very similar to that of the Diels-Alder reaction. Such an expectation is reinforced by frontier orbital theory, which treats both reactions in very much the same way (see Ref. 32). The only significant differences are related to the fact that the lowest unoccupied MO (LUMO) for a linear 1,3-dipole... 

The change in frontier orbitals by coordination of a Lewis acid to the dipole... 

The 1,3-dipolar cycloaddition of organic azides with nitriles could give rise to two regioisomers. Since organic azides are Type II 1,3-dipoles on the Sustmann classification (approximately equal HOMO-LUMO gaps between the interacting frontier orbital pairs) the reactions could be dipole HOMO or LUMO controled and the regioselectivity should be determined by the orbital coefficients for the dominant HOMO-LUMO interaction. Such systems show U-shaped kinetic curves in their... 

Due to the increased reactivity of the reaction in the presence of a Lewis acid, the reaction scope was extended to singly activated alkenes. Previous results had shown either no reaction or extremely poor yields. However, under the Lewis acid catalyzed conditions, acrylonitrile furnished a 1 1, endo/exo mixture of products. The addition of the catalyst gave unexpected regiochemistry in the reaction, which is analogous with results described in Grigg s metal catalyzed reactions. These observations in the reversal of regio- and stereocontrol of the reactions were rationalized by a reversal of the dominant, interacting frontier orbitals to a LUMO dipole-HOMO dipolarophile combination due to the ylide-catalyst complex. This complex resulted in a further withdrawal of electrons from the azomethine ylide. 

Figure 5 Calculated (AMI) heats of formation AHf), dipole moments (/r), and frontier orbital coefficient and energies (e) for methyl esters 31a and 8a.

The reactivity and regioselectivity of 1,3-dipolar cycloadditions have been discussed in terms of the frontier orbitals [271]. Most of the features may be understood on the basis of simple Hfickel MO theory. The HOMO and LUMO n orbitals and n orbital energies for all 18 combinations of the parent dipoles are shown in Figure 12.8. The frontier orbitals of many of the 1,3-dipoles have previously been derived by CNDO/2 and extended Hfickel theory [272]. The first six structures, all of 16-electron type, are shown in greater detail ... 

The structural requirements of the mesomeric betaines described in Section III endow these molecules with reactive -electron systems whose orbital symmetries are suitable for participation in a variety of pericyclic reactions. In particular, many betaines undergo 1,3-dipolar cycloaddition reactions giving stable adducts. Since these reactions are moderately exothermic, the transition state can be expected to occur early in the reaction and the magnitude of the frontier orbital interactions, as 1,3-dipole and 1,3-dipolarophile approach, can be expected to influence the energy of the transition state—and therefore the reaction rate and the structure of the product. This is the essence of frontier molecular orbital (EMO) theory, several accounts of which have been published. 16.317 application of the FMO method to the pericyclic reactions of mesomeric betaines has met with considerable success. The following section describes how the reactivity, electroselectivity, and regioselectivity of these molecules have been rationalized. 

The pattern that emerges is that dipoles calculated to have HOMO are the ones that react faster (or only) with dipolarop Z-substituents, and dipoles calculated to have a low energy LI that react faster (or only) with dipolarophiles that have X-s addition, the polarization deduced for the frontier orbitals mat extent the regioselectivity observed in their reactions. The la dipoles, and the extended range created by the addition of substituents, make the subject too large to be covered any moi is enough to know that information is available if you ever nee<... 

The frontier orbital model predicts regioselectivity by determining the relative magnitudes of the coefficients in the HOMO and LUMO of the 1,3-dipole and dipolarophile.65,66 The favored cycloadduct will be that formed by the privileged union of the atoms with the largest coefficients.51,54,58 If the energy of interaction is very small for both possible orientations, addition occurs in both directions and two isomeric triazolines will be obtained.54,67... 

The frontier orbital interactions which favored conformation 3 in propanal also stabilize conformation 8. However, 8 is destabilized by dipole-dipole interaction, whereas conformations 9 and 10 are stabilized by other factors. Thus, the CC1 bond is highly polar and moderately strong (78 kcal mol-1), so it has a low-lying C ccl orbital. This permits a stabilizing rcco-0 ccl interaction in conformation 9. 

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