Some examples of Diels-Alder reactions

Indole-2,3-quinodimethanes [44] 44 are bicyclic outer-ring dienes that are widely used to prepare a variety of heterocyclic polycyclic compounds. These dienes, generated by extrusion of CO2 from lactones, are then trapped by dienophiles. Some examples of Diels Alder reactions of the dienes 44 are reported in Scheme 2.19. 

Good yields and high diastereoselectivities were obtained by using zeolites in combination with Lewis-acid catalyst [21]. Table 4.7 illustrates some examples of Diels-Alder reactions of cyclopentadiene, cyclohexadiene and furan with methyl acrylate. Na-Y and Ce-Y zeolites gave excellent results for the cycloadditions of carbocyclic dienes, and combining these zeolites with anhydrous ZnBr2 further enhanced the endo diastereoselectivity of the reaction. An exception is the cycloaddition of furan that occurred considerably faster and with better yield, in comparison with the classic procedure [22], when performed in the presence of sole zeolites. 

Aldehydes bearing electron-withdrawing substituents are reactive as hetoxxlienophiles under mild conditions with a range of 1,3-dienes. In particular, glyoxylate derivatives have been widely used in these cycloadditions. Some examples of Diels -Alder reactions of this type are shown in equations (68), (69) and (70). As can be seen, these reactions occur at relatively low temperatures and are regioselective. ... 

No reaction has been found with simple vinylpyrroles and TCNE. Nevertheless, there are examples of Diels-Alder reaction of some protoporphyrins with this dienophile. It was first reported [73JCS(P1)1424] that compound 184 reacted with TCNE in refluxing chloroform, giving the cycloadduct 185 in 56% yield. A later study reexamined the reaction and found more complicated chemistry (80JOC5196). In initial experiments, reactions of TCNE with protoporphyrin di-ter/-butyl ester were shown to give three major products, 186,187, and 188 but depending on the conditions of the reaction, time, solvent or amount of TCNE, the results were different. The authors also characterized compounds 189 and 190. 

Since their introduction in 1962 by Cookson, 4-substituted 1,2,4-triazo-line-3,5-diones have become some of the most widely used dienophiles in organic chemistry.48 This type of dienophile has found such extensive use that it is not possible to more than touch on its applications here.49 Previous reviews contain more detailed information. -29-30b Table 6-IV contains a few recent representative examples of Diels-Alder reactions with... 

Examples of some compounds that exhibit a high level of dienophilic reactivity are collected in Table 7.1 and examples of Diels-Alder reactions of several of them... 

Further examples of Diels-Alder cycloaddition reactions with small or negligible rate solvent effects can be found in the literature [531-535], The thermolysis of 7-oxabicyclo[2.2.1]hept-5-ene derivatives is an example of a solvent-independent retro-Diels-Alder reaction [537]. For some theoretical treatments of the solvent influence on Diels-Alder cycloaddition reactions, which, in general, confirm their small solvent-dependence, see references [536, 797-799]. 

However, catalysis of Diels-Alder reactions is satisfactory only with specific dienophiles, for example, the two cited in the examples, acrolein, and acrylic acid. Another limitation is that some dienes polymerize in the presence of a Friedel-Crafts catalyst. 

However, [4 + 2] cycloadditions are usually more rapid than the corresponding ene reaction. Table 3-III shows some representative examples of Diels-Alder cycloadditions of acylnitroso dienophiles.38... 

The use of alumina and silica to promote Diels-Alder reactions was first reported by Hudlicky [24]. The reactions of 1-acetoxy-l,3-butadiene with tetrafluoro-p-benzoquinone or / -benzoquinone were considerably accelerated when they occurred inside the pores of the adsorbents. Several other silica- or alumina-catalyzed Diels-Alder reactions, dealing either with investigation of standard model reactions [25] or of reactions of more synthetic utility, were subsequently described. For example, neutral alumina catalyzed the intramolecular reaction of a tetraene to the verrucarol skeleton [26] (Scheme 3). The catalytic action was observed in an attempt to isolate the tetraene by column chromatography. A variety of Diels-Alder reactions were accelerated by silica or the more basic Florisil (Mg0.Si02) in the absence of solvent [27-30]. Table 3 gives some examples of these reactions, which are thought to be catalyzed via multicentered donor-acceptor interactions of the substrates with the active sites of the surface of the adsorbents. 

Some ionic liquids are soluble in nonpolar organic solvents and can therefore be used as microwave coupling agents when microwave-transparent solvents are employed. For example, in Diels-Alder reactions, when adding ionic liquids to toluene, the temperature can reach 195 °C within 150 s of irradiation in contrast to 109 °C without ionic liquids [24]. Leadbeater et al. used this method to increase the rate of the Diels-Alder reaction (Scheme 11.1) (see Chapter 7 of this book). 

For some time it has been known that many pericyclic reactions can be greatly accelerated if they are run under single electron transfer (SET) conditions (also known as electron transfer catalysis, ETC). Examples include Diels-Alder reactions, electrocyclic openings of cyclobutenes, and retro [2-1-2] cycloadditions. From the beginning it has been debated whether these SET reactions really are concerted processes with aromatic transition states, or whether they are better thought of as stepwise processes involving radical cation intermediates. 

Concerted reactions are commonly used to join carbons. For example, the Diels-Alder reaction is the formation of a cyclohexene from a diene and an alkene. Usually the alkene is rendered electrophilic by conjugation with a carbonyl group, and the diene may be rendered nucleophilic by electron-donating substituents. In the case shown in Equation 7.38 the alkene is further electron depleted by association with a Lewis acid [64], a common technique for accelerating Diels-Alder reactions. In some cases, the alkene is nucleophilic and the diene is electrophilic as in Equation 7.39 [65]. Examples of this sort are called reverse-electron-demand Diels-Alder reactions. It is important to point out here that the concerted reactions differ from the foregoing in that no carbanion or cation intermediate is involved, and in many cases, electrophilic and nucleophilic factors are not present, as in the very favorable dimerization of cyclopentadiene. These reactions are covered in more detail in Chapter 5. 

The influence of pressure on organic reactions catalyzed by chiral metal-free organic molecules was studied for selected asymmetric Michael, Baylis-Hillman, aldol, Mannich, Friedel-Crafls, and Diels-Alder reactions-the essential part of this work was done in Japan. In the early stages of those investigations the high-pressure technique was applied to reactions catalyzed by cinchona alkaloids and in most cases low or moderate enantioselectivities were observed. Since 2002 some examples of high-pressure reactions catalyzed by proUne, thioureas, and modified cinchona alkaloids have appeared. 

The first example of enantioselective catalysis of a Diels-Alder reaction was reported in 1979 . Since then, an extensive set of successful chiral Lewis-acid catalysts has been prepared. Some selected examples will be presented here together with their mechanistic interpretation. For a more complete... 

This goal might well be achieved by introducing an auxiliary that aids the coordination to the catalyst. After completion of the Diels-Alder reaction and removal of the auxiliary the desired adduct is obtained. This approach is summarised in Scheme 4.6. Some examples in which a temporary additional coordination site has been introduced to aid a catalytic reaction have been reported in the literature and are described in Section 4.2.1. Section 4.2.2 relates an attempt to use (2-pyridyl)hydrazone as coordinating auxiliary for the Lewis-acid catalysed 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).

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