Diels-Alder Reactions in Alternative Media

Electron-withdrawing groups attached to the dienophile accelerate the rate of the reaction, donating groups decrease it. For the diene, the opposite is true. Because of the high regiospecificity and the tolerance of a wide number of functional groups, the Diels-Alder reaction is of considerable synthetic importance. 

Chemistry in Alternative Reaction Media D. Adams, P. Dyson and S. Tavener 2004 John Wiley Sons, Ltd ISBNs 0-471-49848-3 (Cloth) 0-471-49849-1 (Paper) 

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It is believed that clay minerals promote organic reactions via an acid catalysis [2a]. They are often activated by doping with transition metals to enrich the number of Lewis-acid sites by cationic exchange [4]. Alternative radical pathways have also been proposed [5] in agreement with the observation that clay-catalyzed Diels-Alder reactions are accelerated in the presence of radical sources [6], Montmorillonite K-10 doped with Fe(III) efficiently catalyzes the Diels-Alder reaction of cyclopentadiene (1) with methyl vinyl ketone at room temperature [7] (Table 4.1). In water the diastereoselectivity is higher than in organic media in the absence of clay the cycloaddition proceeds at a much slower rate. 

Diels-Alder reactions have been performed in most alternative reaction media. For certain substrates this reaction is significantly accelerated in fluorous solvents (Figure 1.9) This has been ascribed to a fluorophobic effect, analogous to the better-known hydrophobic effect where there is an inverse relationship between reaction rate and the solubility of reagents. However, it should be noted that in general cycloaddition reactions (including Diels-Alder reactions) are faster in water and this can be attributed to additional hydrogen bond stabilization of the transition state. 

Liquid polyethylene glycol in organic synthesis. Three main types of reaction have been studied substitution, oxidation and reduction (Figure 8.5). The Diels Alder reaction is frequently used as a benchmark for alternative reaction media. For the reaction of 2,3-dimethyl-1,3-butadiene with nitrosobenzene in PEG 300 or PPG 425, a 3.3-fold increase in rate was seen compared with dichloromethane and a 2.5-fold increase compared with ethanol. It has also been shown more recently that in comparison to conventional solvents, the transition state for the Diels-Alder reaction is stabilized in aqueous PEG solutions and this results in a lower activation energy. ... 

Non-chloroaluminate ILs, which are in general poor nucleophiles, have proven to be attractive alternative media for Lewis acid catalyzed reactions. ILs may have a reaction rate accelerating effect, and they may improve selectivity and facilitate catalyst recovery. This is the case for scandium triflate catalyzed Diels-Alder cycloaddition [8,9], three-component (aldehyde, aniline, triethylphosphite) synthesis of a-aminophosphonates [10], Claisen rearrangement and cyclization reactions [11], or Friedel-Crafts reactions [12, 13]. 

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