LUMO diene-controlled

These results, including the fact that the cycloaddition rates are independent of solvent polarity, are consistent with a concerted LUMO-diene controlled process. This assumption is also supported by calculations [79]. Interestingly, the... 

Lewis acids have been widely used to catalyze Diels-Alder reactions when thermal conditions were not efficient [43]. A limitation of the Lewis acid catalyzed Diels-Alder cycloaddition reaction has often been found to be due to the sensitivity of the substrates to the strongly acidic media. For instance, when considering the addition of phenylacetylene derivatives to 1-silyloxypyrrole, it was found that the Lewis acids (AICI3, BF3, TiCU) led to decomposition of starting materials, while the thermal processes afforded only negligible amounts of the desired cycloadduct [44]. The successful preparation of the cycloadduct product was achieved with lithium perchlorate in ether. This approach did not produce a very acidic reaction medium, but considerably lowered the LUMO pyrrole energy, almost as much as protonation by itself (Table 14). The final effect was that the reaction became a strongly LUMO diene controlled Diels-Alder reaction. 

A more reliable study of the 1,2-diazole tautomer reactivity as a diene for the Diels-Alder reaction was carried out by the MP2/6-31+G(d) theory model. The predicted order of reactivity was similar to the one generated by the AMI study [2H]-1,2-diazole (0.0 kcal/mol) [4H]-1,2-diazole (-24.3 kcal/mol), and [3LT1-1,2-diazole (-29.1 kcal/mol). Because the reaction is LUMO diene controlled by... 

As in the case of unsubstituted [4//]-l,2-diazole, 3,5-dichloro-[4H]-l,2-diazole is a LUMO diene controlled cycloaddition reaction. Necessary FMO changes for reactants in the exo and endo addition of cyclopropane to 3,5-dichloro-[4H]-1,2-diazole to adapt the transition state structures are presented in Table 48. The required energy is too small to be compared with the other heterocycles presented in this study (for example see Table 41). Furthermore, the endo addition of cyclopropane should be favored over the exo cycloaddition. 

As we have demonstrated with the example of [4//]-l,2-diazole as a diene for the Diels-Alder addition, there are two critical prerequisites for any five-membered heterocycle to become a diene for the Diels alder reaction the aromaticity of the heterocycle should be diminished as much as possible and the formation of two CC bonds is preferable over formation of a C-heteroatom bond. Because these reactions are LUMO diene controlled, it is helpful if electron-withdrawing substituents are attached to the heterocyclic ring, all of which may be accomplished if the nitrogen in position one of 1,2-diazole and 1,3,4-triazole is quaternized. We expect that these heterocycles should be exceptionally good dienes that promote the formation of the endo cycloadduct due to strong steric repulsion interactions between methyl groups of quaternized heterocycles and the dienophiles. To reinforce the existence of a high localization of the double bonds in... 

Certainly a better insight into the reactivity of these two quaternized heterocycles can be obtained through evaluation of the activation barriers for cycloaddition (Table 51). It must be mentioned that transition state structures with these two quaternized heterocycles in reaction with acetylene, ethylene, and cyclopentene are very similar to the transition state structure with unquatemized heterocycles. As predicted on the basis of the bond order distribution in the heterocyclic ring, these two heterocycles were very reactive dienes for the Diels-Alder reactions. The computed energies were in full agreement with the bond order uniformity presented in Table 50. Both heterocycles had low 7t-density on the ring, but the A //-dimethyl-l,3,4-triazolium cation was more electron deficient (SBO = 6.530, Table 50), with a higher 7t-orbital localization (BOD = 2.330, Table 50). Because the reaction is LUMO diene controlled, the activation barriers with the A(,A(-dimethyl-l,3,4-triazolium cation must be lower in comparison to activation... 

The reactivity in Diels-Alder reactions is controlled by the HOMO-LUMO energy gap between the reagents. Generally, the small energy-separation is found between the HOMO of the diene and the LUMO of the dienophile and we talk about normal Diels-Alder reactivity. High HOMO dienes and low LUMO dienophiles are ideal substrates for these types of reactions. By contrast, electron-deficient dienes like 1 have low HOMOs and are more prone to participate in inverse electron demand Diels-Alder. In these cases the interaction HOMO dienophile-LUMO diene controls the process. 

Ab initio calculations on aza-Diels-Alder reactions of electron-deficient imines with buta-l,3-diene show that these reactions are HOMO (diene)-LUMO(dienophile)-controlled and that electron-deficient imines should be more reactive than alkyl-or aryl-imines. The Diels-Alder reaction of r-butyl 2//-azirine-3-carboxylate (80) proceeds with high diastereoselectivity with electron-rich dienes (81) (Scheme 28). The hetero-Diels-Alder additions of imines with sterically demanding dienes yield perhydroquinolines bearing an angular methyl group. The asymmetric hetero-Diels-Alder reaction between alkenyloxazolines and isocyanates produces diastereometri-cally pure oxazolo[3,2-c]pyrimidines. °... 

Because of the strong rr-deficiency of most six-membered heteroaromatic compounds, cycloadditions of this type belong to Diels-Alder reactions with inverse electron demands in other words, they are LUMO -HOMOp, controlled reactions (for review see (B-87MI 502-08)). Acceptor substituents in the heterocyclic diene and donor substituents in the dienophile accelerate the reaction, as shown by kinetic data (83TL1481,84TL2541,90TL6851). 

Five-membered heteroaromatic systems that possess an electron-deficient azadiene substructure, e.g., oxazoles and thiazoles, are suitable for participation in Diels-Alder reactions with inverse electron-demand [49JA3062 59JA4342 62AG(E)329]. The introduction of strongly electron-donating substituents in many cases is sufficient to overcome the electron-deficient nature of the azadiene moiety and permits normal HOMO diene/ LUMO dienophile controlled Diels-Alder reactions (87MI6). 

Studies on the addition of acyl nitroso compounds to 1,2-dihydropyridine derivatives have been described, and some of the results are shown in equation (38). It was found that the nitroso dienophiles produced from hydroxamic acids (100) reacted with dihydropyridine (99) at di erent rates and afforded the ratios of regioisomeric products indicated. Both the relative reaction rates and orientation are in accord with a HOMO-diene/LUMO-dienophile controlled process. 

Alkyl-substituted selenoaldehydes only cycloadd to certain reactive dienes such as cyclopentadiene or 1,3-diphenylisobenzofuran. On the other hand, selenoaldehydes bearing electron-withdrawing groups react with a wide range of electron-rich dienes. One method of formation of this type of dienophile and some regiochemical results with an unsymmetrical 1,3-diene are shown in equation (106). The orientation observed here is in accord with a dienophile-LUMO/diene-HOMO controlled process. 

Because these transition state structures are symmetric, all previously used approaches for determining relative reactivity of the heterocycles should be applicable in these cases. The cycloaddition is a HOMO dienophile and LUMO heterocycle (diene) controlled cycloaddition reaction with exceptionally low demand for orbital energy changes in reactants to achieve the electronic contribution present in the transition state structure (Table 41). There is no doubt that 1,3,4-oxadiazole is the most reactive of all five-membered heterocycles with three heteroatoms. However, the question remains as to whether this heterocycle is more reactive than, for instance, furan or even cyclopentadiene. To answer this question, the deviation of bond order uniformity in the six-membered ring being formed was computed (Table 42). The bond order uniformity selected 1,3,4-... 

As mentioned above, the cycloaddition reaction with 1,3,4-oxadiazole is predicted to be LUMO diene (heterocycle) controlled. That definitely suggests that with electron-withdrawing substituents in the two and five positions of the heterocycle ring, the heterocycle should become more reactive as a diene for Diels-Alder reactions. To study the usefulness of 1,3,4-oxadiazole and its derivatives as dienes for the Diels-Alder reaction, we are presenting the results of our theoretical study of the cyclopropene addition to 2,5-di(trifluoromethyl)-l,3,4-oxadiazole. The AMI computed FMO energy gap for this reaction pair was only 8.00266 eV in comparison to 9.64149 eV FMO energy gap between LUMO of 1,3,4-oxadiazole and HOMO of cyclopropene. Therefore, the computed activation barrier for the cyclopropene addition to 2,5-bis(trifluoromethyl)-1,3,4-oxadiazole should be very... 

To confirm these findings, we have computed activation barriers for the acetylene, ethylene and cyclopropane additions to 3,5-dichloro-[4H]-1,2-diazole. The computed activation barriers (Table 49) were even slightly lower than the activation barriers for same reaction with 4,4-dimethyl-[4H]-l,2-diazole as a diene (Table 47). This is a reasonable observation because the cycloaddition reaction is LUMO heterocycle (diene) controlled. The LUMO energy of 3,5-dichloro-[4fir -1,2-diazole was substantially lower than the LUMO energy of 4,4-dimethyl-[4/Tl-1,2-diazole. Subsequently, with a modest activation barrier of 20.1 kcal/mol, even poor dienophiles such as acetylene should be capable to react with 3,5-dichloro-[4i/]-1,2-diazole as a diene in the Diels-Alder reactions (Table 49). 

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