Diel’s Alder Reaction

Fig. 5.3.1. Diel s-Alder reaction of anthracene (diene) and maleimide (dienophile).

The Wadsworth-Emmons reaction of the aldehyde (190) with the complex phosphonate (191) has been used to construct the Cio-Cn double bond in a convergent synthesis of lacrimin A (192) (Scheme 27). Phosphonate-based olefination has been extensively used in the synthesis of cytohalasans (e.g. 193), a group of biologically active fungal metabolites. 12 The phosphonate (194) has been used to construct a triene function which ultimately forms the tricyclic structure through an intramolecular Diel s Alder reaction. 14,15-Dehydroforskolin (196) has been prepared by the base-induced reaction of the aldehyde (195) with dimethyl diazomethylphosphonate.l 13 Under certain conditions the phosphonate (197) can be isolated and this provides evidence for the involvement of the Wadsworth-Emmons intermediate (198) in the reaction. The phosphonate... 

Singlet oxygen reacts with fiufuryl alcohol (a 1,3-diene) and 2,5-dimethyl furan (also used as a probe) in what is termed by the organic chemist as a Diel s-Alder reaction to produce an endoperoxide that reacts further to give the products illustrated. The reaction with an alkyl substituted alkene involves abstraction of the allylic hydrogen and recombination to form an... 

The neutral ionic liquids are excellent solvents for the Diels-Alder reaction and are better than the conventional solvents and even water (see Section 12.2). Addition of a mild Lewis acid like Znl increases the selectivities in this reaction. A special advantage of this system is that the ionic liquid and catalyst can be recycled and reused after extraction or direct distillation of the product from the ionic liquid. A typical Diel s-Alder reaction is given (Scheme 6). 

Cycloaddition reactions are one of the most important organic chemical reactions. Diel s-Alder reaction, is the most popular example of cycloaddition reaction and known to every serious student of organic chemistry. Cycloaddition provides route to synthesise cyclic compounds from acyclic reactants. 

The transition state in a Diels-Alder reaction involves transfer of electrons from one molecule to the other. Using SpartanView to compare electrostatic potential maps of cyclopentadiene, tetracyanoethylcne, and their Diel.s-Alder transition state, describe the direction of electron transfer. 

W C, A Tempcz)rrk, R C Hawley and T Hendrickson 1990. Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. Journal of the American Chemical Society 112 6127-6129. ensson M, S Humbel, R D J Froese, T Matsubara, S Sieber and K Morokuma 1996. ONIOM A Multilayered Integrated MO + MM Method for Geometry Optimisations and Single Point Energy Predictions. A Test for Diels-Alder Reactions and Pt(P(t-Bu)3)2 + H2 Oxidative Addition. Journal of Physical Chemistry 100 19357-19363. 

Recently Desimoni et used the same bis(oxazoline) ligand in the magnesium(II) catalysed Diels-Alder reaction of the N-acyloxazolidinone depicted in Scheme 3.4. In dichloromethane a modest preference was observed for the formation of the S-enantiomer. Interestingly, upon addition of two equivalents of water, the R-enantiomer was obtained in excess. This remarkable observation was interpreted in terms of a change from tetrahedral to octahedral coordination upon the introduction of the strongly coordinating water molecules. 

Figure 5.4. Plot of the apparent second-order rate constant, kapp (= kotJ[5.2]i) versus the concentration of surfactant for the Diels-Alder reaction of S.lg with 5.2 in CTAB solution at 25 C. The inset shows the treatment of these data using Equation 5.6. From slope and intercut P j can be calculated (see Table 5.2).

Table 5.5. Influence of micelles of Cu(DS)2, CTAB and C12E7 on the apparent second-order rate constants (M s" ) for the copper(II) catalysed Diels-Alder reaction of 5.1c, 5.If and 5.1 g with 5.2 at 25 C .

Note that the stereochemistry comes out right. H s a and b are cis because they were cis in the starting quinone and the Diels-Alder reaction is stereospecific in this respect. H is also cis to and H " because the Diels-Alder reaction is stereoselectively endo. These points are described in more detail in Norman p.284-6 and explained in Ian Fleming Frontier Orbitals and Organic Chemical Reactions, Wiley 1976, p. 106-109. How would you make diene A ... 

A major difficulty with the Diels-Alder reaction is its sensitivity to sterical hindrance. Tri- and tetrasubstituted olefins or dienes with bulky substituents at the terminal carbons react only very slowly. Therefore bicyclic compounds with polar reactions are more suitable for such target molecules, e.g. steroids. There exist, however, several exceptions, e. g. a reaction of a tetrasubstituted alkene with a 1,1-disubstituted diene to produce a cyclohexene intermediate containing three contiguous quaternary carbon atoms (S. Danishefsky, 1979). This reaction was assisted by large polarity differences between the electron rich diene and the electron deficient ene component. 

As final examples, the intramolecular cyclopropane formation from cycloolefins with diazo groups (S.D. Burke, 1979), intramolecular cyclobutane formation by photochemical cycloaddition (p. 78, 297f., section 4.9), and intramolecular Diels-Alder reactions (p. 153f, 335ff.) are mentioned. The application of these three cycloaddition reactions has led to an enormous variety of exotic polycycles (E.J. Corey, 1967A). 

Since the six carbons shown above have 10 additional bonds, the variety of substituents they carry or the structures they can be a part of is quite varied, making the Diels-Alder reaction a powerful synthetic tool in organic chemistry. A moment s reflection will convince us that a molecule like structure [XVI] is monofunctional from the point of view of the Diels-Alder condensation. If the Diels-Alder reaction is to be used for the preparation of polymers, the reactants must be bis-dienes and bis-dienophiles. If the diene, the dienophile, or both are part of a ring system to begin with, a polycyclic product results. One of the first high molecular weight polymers prepared by this synthetic route was the product resulting from the reaction of 2-vinyl butadiene [XIX] and benzoquinone [XX] ... 

Acrolein a.s Dienophile. The participation of acrolein as the dienophile in Diels-Alder reactions is, in general, an exothermic process. Dienes such as cyclopentadiene and l-dieth5laniino-l,3-butadiene react rapidly with acrolein at room temperature. 

Another stereochemical feature of the Diels-Alder reaction is addressed by the Alder rule. The empirical observation is that if two isomeric adducts are possible, the one that has an unsaturated substituent(s) on the alkene oriented toward the newly formed cyclohexene double bond is the preferred product. The two alternative transition states are referred to as the endo and exo transition states ... 

Lastly, in perfluorobutadiene s codimerization reaction with butadiene, a significant amount of Diels-Alder adduct is obtained, with the perfluorodiene acting as the diene component [125] (equation 105)... 

Step through the sequence of structures corresponding to the combination of c/s -1,3-butadiene and ethene to give cyclohexene (Diels-Alder reaction). 

Tables 12.1-12.3 below give some examples of the magnitude of each term for two bimolecular reactions (Diels-Alder and Sn2 reactions, forming either one or two molecules as the product) and a unimolecular rearrangement (Claisen reaction). All values have been calculated at the MP2 level with the 6-31G(d) basis for the Diels-Alder and Claisen reactions, and the 6-31+G(d) basis for the S l reaction. The values are given in kcal/mol at a temperature of 300 K (RT = 0.60 kcal/mol).

The course of the reaction may involve either the acylation of the ketone to a -diketonic intermediate following thereupon the pathway in Section II, C, 2, a, or alternatively the condensation of two moles of ketone to yield an intermediate dypnone which then undergoes acylation following the pathway in Section II,C, l,a. Dilthey and Fischer thought the first alternative more plausible, on the basis of reaction yields, and this lead them to explore the pathway in Section II,C,2,a. Schneider and Ross and Diels and Alder believed that the second alternative operates. Both views are plausible since acylations of methyl ketones to S-diketones are known to take place in the conditions of this reaction, and dypnone ha.s been isolated from acetophenone on treatment with Friedel-Crafts catalysts, in the absence of an acid anhydride or chloride (an excess of catalyst... 

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