Regioselectivity orbital coefficients

The FMO coefficients also allow cpralitative prediction of the kinetically controlled regioselectivity, which needs to be considered for asymmetric dienes in combination with asymmetric dienophiles (A and B in Scheme 1.1). There is a preference for formation of a o-bond between the termini with the most extreme orbital coefficients ... 

The regioselectivity benefits from the increased polarisation of the alkene moiety, reflected in the increased difference in the orbital coefficients on carbon 1 and 2. The increase in endo-exo selectivity is a result of an increased secondary orbital interaction that can be attributed to the increased orbital coefficient on the carbonyl carbon ". Also increased dipolar interactions, as a result of an increased polarisation, will contribute. Interestingly, Yamamoto has demonstrated that by usirg a very bulky catalyst the endo-pathway can be blocked and an excess of exo product can be obtained The increased di as tereo facial selectivity has been attributed to a more compact transition state for the catalysed reaction as a result of more efficient primary and secondary orbital interactions as well as conformational changes in the complexed dienophile" . Calculations show that, with the polarisation of the dienophile, the extent of asynchronicity in the activated complex increases . Some authors even report a zwitteriorric character of the activated complex of the Lewis-acid catalysed reaction " . Currently, Lewis-acid catalysis of Diels-Alder reactions is everyday practice in synthetic organic chemistry. 

The observed regioselectivity can be explained by taking into account the frontier orbital coefficients of the reactants. 

The ortho-para rule is explained by FMO theory on the basis of the orbital coefficients of the atoms forming the cr-bonds. The regiochemistry is determined by the overlap of the orbitals that have larger coefficients (larger lobes in Scheme 1.15). The greater the difference between the orbital coefficients of the two end atoms of diene and two atoms of dienophile, which form the two cr-bonds, the more regioselective the cycloaddition. 

The reactions of 521 with 1,3-dienes were found to proceed exclusively in an [8 + 2] addition mode. The reactions were completely site and regioselective, as exemplified by the reaction between 521 and 2-methyl-l,3-pentadiene (525) which gave 526 after loss of CO2 (equation 152). The regiochemistry observed was in agreement with the frontier orbital coefficients calculated with semi-empirical methods. 

The regioselectivity observed was in agreement with the calculated orbital coefficients for the HOMO of heptafulvene 534 and the LUMOs of the polyenophiles. The largest coefficient in the HOMO of 534 is at C(8). The reactions of nitroethene and (E)-fi-nitrostyrene with 533 (entries 4 and 5) afforded merely exo adducts, the two isomers arising from attack of the polyenophile at the two different sites of 534. 

While the reactivity is determined by the HOMO-LUMO energy separation, the selectivity is dominated by the orbital coefficients64. As a consequence, thekinetically controlled regioselectivity of the Diels-Alder ring closure, and thus the formation of the two new cr-bonds (between atoms 1,6 and 4,5 or between atoms 1,5 and 4,6 in Scheme 1), is determined by the FMO coefficients at the terminal carbon atoms of the diene and the dienophile. The FMO predictions boil down to the fact that the formation of cr-bonds between carbon atoms with similar orbital coefficients is preferred. The magnitudes of these coefficients... 

The influence of the solvent on the regioselectivity is perfectly described by FMO theory142. As mentioned above, the regioselectivity is determined by orbital coefficients on the terminal carbons of the diene and dienophile which, in turn, are determined by the electronic substituent effects. These can be modified by electron donation or electron withdrawal by the solvent or additives like Lewis acids. 

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... 

The product-determining role of the LUMO can also explain the regioselective capture of other radical cations, including the nucleophilic attack on l-aryl-2-alkylcyclopropanes (112 +). The SOMO and LUMO of disubstituted cyclopropane radical cations (e.g., 1,2-dimethylcyclopropane Fig 6.17) suggest that the observed regioselectivity reflects electronic factors capture at the unsubstituted cyclopropane carbon is unlikely, since neither SOMO nor LUMO have orbital coefficients at C3. ... 

Frontier molecular orbital (FMO) theory has been successful in rationalizing the reactivity, electroselectivity, and regioselectivity of many heterocycles, including mesomeric betaines. To apply FMO theory, some knowledge of the frontier orbital coefficients and energies is necessary, and it is useful to draw some general conclusions about the frontier orbitals in mesomeric betaines. 

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). 

The regiochemistry of Diels-Alder reactions with 3.3.3-trifluoropropene (1) shows that the inductive effect of a trifluoromethyl group increases the magnitude of the molecular orbital coefficient of the unsubstituted terminus, but the effect is not great enough to achieve high regioselectivity with dienes other than l-methoxy-3-(trimethylsiloxy)buta-l,3-diene (Danishefsky s diene, 4) compare the reaction of 1 with 2, 3, and 4. ... 

Nitrone 1 reacts with the parent 3,3,3-trifluoropropenc and with various 3,3,3-trifluoro-propenes which arc substituted in the 1-position with another electron-withdrawing group (ester, nitro or sulfone). Regioselectivity depends on the LUMO coefficient of C2 which is larger for sulfones and nitro compounds. However, with 3,3,3-trifluoropropene the predominant formation of the 5-(trifluoromethyl)isoxazolidine is not explained by orbital coefficients, but by stcric hindrance. 

MO calculations that give tt-orbital coefficients for dienes and dienophiles are beyond the scope of this book. However, there is a simple mnemonic trick that will predict regioselectivity in many cases. It involves drawing the four possible diradical intermediates that can be formed by homolytic bonding at one end of each reactant. Always remember, this is just a mnemonic trick most Diels-Alder reactions are concerted and do not proceed through a diradical intermediate. 

The formation of cyclobutanes starting from a,P-unsaturated carbonyl compounds and olefins is referred to as the de Mayo reaction. The carbonyl component is excited upon irradiation by ti <—ti transition. The regioselectivity is determined by orbital coefficients and polarity effects that depend on the solvent, but the stereochemical information of the olefin is not preserved in intermolecular processes, indicating the non-concerted character of a triplet reaction. In this case 1,4-biradical intermediates are formed and the most stable one determines the stereochemistry of the main product. The cycloadducts of pentanones are most often cis-fused while hexanones preferentially give transcycloadducts. ... 

---