Molecular-orbital calculations Diels-Alder reactions

Fig. 22 The Diels-Alder cycloaddition between the dienophile [54] and diene [53 yields two diastereoisomers [55] and [56]. Attenuated substrate analogues [57] and [58 were used in molecular orbital calculations of this reaction.

Molecular orbital calculations indicate that cyclo C-18 carbyne should be relatively stable and experimental evidence for cyclocarbynes has been found [25], Fig. 3B. Diederich et al [25] synthesised a precursor of cyclo C-18 and showed by laser flash heating and time-of flight mass spectrometry that a series of retro Diels-Alder reactions occurred leading to cyclo C-18 as the predominant fragmentation pattern. Diederich has also presented a fascinating review of possible cyclic all-carbon molecules and other carbon-rich nanometre-sized carbon networks that may be susceptible to synthesis using organic chemical techniques [26]. 

This chapter will try to cover some developments in the theoretical understanding of metal-catalyzed cycloaddition reactions. The reactions to be discussed below are related to the other chapters in this book in an attempt to obtain a coherent picture of the metal-catalyzed reactions discussed. The intention with this chapter is not to go into details of the theoretical methods used for the calculations - the reader must go to the original literature to obtain this information. The examples chosen are related to the different chapters, i.e. this chapter will cover carbo-Diels-Alder, hetero-Diels-Alder and 1,3-dipolar cycloaddition reactions. Each section will start with a description of the reactions considered, based on the frontier molecular orbital approach, in an attempt for the reader to understand the basis molecular orbital concepts for the reaction. 

The hetero-Diels-Alder reaction of aldehydes 12 with 2-azabutadienes 13 (Scheme 8.5) has been studied using high-level ab-initio multiconfigurational molecular orbital and density functionality calculation methods [28]. 

Intramolecular inverse electron-demand Diels-Alder reaction of iV-propargyl-2-(pyrimidin-2-yl)pyrrolidine provides an alternative route to pyridopyrrolizines. For example, heating of 130 to 170 °C in nitrobenzene affords the cyclized product with the loss of HCN <1992JOC3000> (Equation 9). The above reference includes molecular orbital (MO) calculations on relative reactivities in this series. 

AMI semi-empirical and B3LYP/6-31G(d)/AMl density functional theory (DFT) computational studies were performed with the purpose of determining which variously substituted 1,3,4-oxadiazoles would participate in Diels-Alder reactions as dienes and under what conditions. Also, bond orders for 1,3,4-oxadiazole and its 2,5-diacetyl, 2,5-dimethyl, 2,5-di(trifluoromethyl), and 2,5-di(methoxycarbonyl) derivatives were calculated <1998JMT153>. The AMI method was also used to evaluate the electronic properties of 2,5-bis[5-(4,5,6,7-tetrahydrobenzo[A thien-2-yl)thien-2-yl]-l,3,4-oxadiazole 8. The experimentally determined redox potentials were compared with the calculated highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO) energies. The performance of the available parameters from AMI was verified with other semi-empirical calculations (PM3, MNDO) as well as by ab initio methods <1998CEJ2211>. 

In the course of investigation of reactivity of the mesoionic compound 44 (Scheme 2) the question arose if this bicyclic system participates in Diels-Alder reactions as an electron-rich or an electron-poor component <1999T13703>. The energy level of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals were calculated by PM3 method. Comparison of these values with those of two different dienophiles (dimethyl acetylenedicarboxylate (DMAD) and 1,1-diethylamino-l-propyne) suggested that a faster cycloaddition can be expected with the electron-rich ynamine, that is, the Diels-Alder reaction of inverse electron demand is preferred. The experimental results seemed to support this assumption. 

Of the many PET Diels-Alder reactions of potential synthetic utility we mention two reactions of vinylindole (103) catalyzed by 2,4,6-tris(4-methoxyphenyl)-pyrylium tetrafluoroborate. With cyclohexadiene, 103 reacts as a diene, giving rise to tetrahydrocarbazole (104) with exocychc dienes, 103 serves as dienophile generating a different tetrahydrocarbazole (105). Molecular orbital calculations provide a rationale for the regio- and diastereoselectivities of these reactions. 

Although exo-endo selectivity in the Diels-Alder reaction of olefinic dienophiles has been extensively studied both experimentally and theoretically [31], exo-endo selectivity of the transition structure in the reaction of acetylenic dienophiles has not previously been investigated, because the adducts produced via exo- or endo-transi-tion-state assembly are identical diastereomerically. We used ab initio molecular orbital calculations at the RHF/6-31G level [32] to identify the transition struetures of simple processes of this type, i.e. acid-free and BFs-promoted reactions of cyclopenta-diene and propynal (Fig. 9). As expected, our calculations showed that the exo transition structures are more stable than the endo structures by 0.8 kcal mol" for the former reaction and by 2.0 and 2.4 kcal moF for anti and syn pairs, respectively, for the latter. These calculations strongly suggest the predominance of an exo transition structure and its enhancement by coordination of the Lewis acid. 

Cyclopentadienone is an elusive compound that has been sought for many years but with little success. Molecular orbital calculations predict that it should be highly reactive, and so it is it exists only as the dimer. The tetraphenyl derivative of this compound is to be synthesized in this experiment. This derivative is stable, and reacts readily with dienophiles. It is used not only for the synthesis of highly aromatic, highly arylated compounds, but also for examination of the mechanism of the Diels-Alder reaction itself. Tetraphenylcyclopentadienone has been carefully studied by means of molecular orbital methods in attempts to understand its unusual reactivity, color, and dipole moment. In Chapter 48 this highly reactive molecule is used to trap the fleeting benzyne to form tetraphenylnaphthalene. Indeed, this reaction constitutes evidence that benzyne does exist. 

Theoretical calculations have also permitted one to understand the simultaneous increase of reactivity and selectivity in Lewis acid catalyzed Diels-Alder reactions . This has been traditionally interpreted by frontier orbital considerations through the destabilization of the dienophile s LUMO and the increase in the asymmetry of molecular orbital coefficients produced by the catalyst. Birney and Houk have correctly reproduced, at the RHF/3-21G level, the lowering of the energy barrier and the increase in the endo selectivity for the reaction between acrolein and butadiene catalyzed by BH3. They have shown that the catalytic effect leads to a more asynchronous mechanism, in which the transition state stmcture presents a large zwitterionic character. Similar results have been recently obtained, at several ab initio levels, for the reaction between sulfur dioxide and isoprene. ... 

On the basis of Monte Carlo simulations [40] and molecular orbital calculations [26a], hydrogen bonding was proposed as the key factor controlling the variation of the acceleration for Diels-Alder reactions in water. Experimental differences of rate acceleration in water-promoted cycloadditions were recently observed [41]. Cycloadditions of cyclopentadiene with acridizinium bromide, acrylonitrile and methyl vinyl ketone were investigated in water and in ethanol for comparison (Scheme 3). Only a modest rate acceleration of 5.3 was found with acridizinium bromide, which was attributed to the absence of hydrogenbonding groups in the reactants. The acceleration factor reaches about 14 with acrylonitrile and 60 with methyl vinyl ketone, which is the best hydrogen-bond acceptor [41]. 

Recently, molecular orbital calculations have been performed on the parent heterocycle.The results of the calculations indicate C-5 and C-7 should be the most reactive sites to electrophilic, nucleophilic, and free-radical attack. The degree of bond fixation evident from bond length calculations suggested that these positions should also act as the termini of a s-butadiene fragment rendering the molecule liable to Diels-Alder-type reactions. 

In order to get more information on these two effects we have performed the Diels-Alder reaction between dihych opyi an and acrolein in the presence of various H-form zeolites such as H-faujasites, H-(t and H-mordenites. This reaction was reported to proceed with difficulty under thermal conditions in the absence of catalyst (11). The catalysts tested in this work differ both in their shape selective as well as their acidic properties. On the other hand, molecular orbital calculations (MNDO) have been performed to account for the experimental results on the uncatalyzed and catalyzed reactions. 

Theoretical quantitative treatments of cycloadditions mainly concern the Diels-Alder reaction. A possible approach is that of calculating the para-localisation energy, that is the variation of Tr-electron energy of the conjugated diene system, when two Tr-electrons are localised upon the atoms, in 1,4-relation to each other, which must form the new tr-bonds. This has been done by Brown , using the molecular orbital method some successful predictions of reactivity and of the positions of addition for polycyclic aromatic hydrocarbons and polyenes were made. This method has also been used by other authors - . 

Geerlings and co-workers examined Diels-Alder reactions of ethylene with quinodimethanes, including 751, using ab initio molecular orbital calculations and density functional theory (DFT). 

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