Micellar catalysis, Diels-Alder reaction

What is the effect of micelles on the aqueous Diels-Alder reaction Can micellar catalysis be combined with Lewis-acid catalysis In Chapter 5 these aspects will discussed. 

This chapter describes the effects of micelles on the Diels-Alder reaction of compounds 5,1 a-g (see Scheme 5.1) with cyclopentadiene (5.2). As far as we know, our study is the first detailed kinetic analysis of micellar catalysis of a Diels-Alder reaction. 

In this section the influence of micelles of cetyltrimethylammonium bromide (CTAB), sodium dodecylsulfate (SDS) and dodecyl heptaoxyethylene ether (C12E7) on the Diels-Alder reaction of 5.1a-g with 5.2 in the absence of Lewis-add catalysts is described (see Scheme 5.1). Note that the dienophiles can be divided into nonionic (5.1a-e), anionic (5.If) and cationic (5.1g) species. A comparison of the effect of nonionic (C12E7), anionic (SDS) and cationic (CTAB) micelles on the rates of their reaction with 5.2 will assess of the importance of electrostatic interactions in micellar catalysis or inhibition. 

Interestingly, at very low concentrations of micellised Qi(DS)2, the rate of the reaction of 5.1a with 5.2 was observed to be zero-order in 5.1 a and only depending on the concentration of Cu(DS)2 and 5.2. This is akin to the turn-over and saturation kinetics exhibited by enzymes. The acceleration relative to the reaction in organic media in the absence of catalyst, also approaches enzyme-like magnitudes compared to the process in acetonitrile (Chapter 2), Cu(DS)2 micelles accelerate the Diels-Alder reaction between 5.1a and 5.2 by a factor of 1.8710 . This extremely high catalytic efficiency shows how a combination of a beneficial aqueous solvent effect, Lewis-acid catalysis and micellar catalysis can lead to tremendous accelerations. 

Finally, in Chapter 5, micellar catalysis of Diels-Alder reactions is discussed. In view of the nonpolar nature of most Diels-Alder reactants, efficient micellar catalysis of this reaction was anticipated However, this has not been observed. The results for the Diels-Alder reaction between cyclopentadiene and substituted 3-phenyl-l-(2-pyridyl)-2-propene-l-one dienophiles, discussed in... 

In summary, the work in this thesis provides an overview of what can be achieved with Lewis-acid and micellar catalysis for Diels-Alder reactions in water as exemplified by the reaction of3-phenyl-l-(2-pyridyl)-2-propene-l-ones with cyclopentadiene. Extension of the observed beneficial effect of water on rates and particularly enantioselectivities to other systems is envisaged. 

Chapter 5 describes a study of the effect of micelles on the Diels-Alder reaction of 1 with 2. Literature studies on micellar catalysis of Diels-Alder reactions invariably failed to reveal significant accelerations. These results are unexpected, since most Diels-Alder reactants have a high affinity for... 

Table 4.16 Micellar catalysis of Diels-Alder reactions of cyclopentadiene (1) with 3-(p-substituted phenyl)- -(2-propen-1-one (113) in water at 25 °C. Relative rate constants ( rei) to the reactions performed in sole water...

The Diels-Alder reaction of nonyl acrylate with cyclopentadiene was used to investigate the effect of homochiral surfactant 114 (Figure 4.5) on the enantioselectivity of the reaction [77]. Performing the reaction at room temperature in aqueous medium at pH 3 and in the presence of lithium chloride, a 2.2 1 mixture of endo/exo adducts was obtained with 75% yield. Only 15% of ee was observed, which compares well with the results quoted for Diels-Alder reactions in cyclodextrins [65d]. Only the endo addition was enantioselective and the R enantiomer was prevalent. This is the first reported aqueous chiral micellar catalysis of a Diels-Alder reaction. 

Chiral surfactants have been used in the aqueous chiral micellar catalysis of a Diels-Alder reaction using an (5)-leucine-derived surfactant (Figure 12.4) to catalyze the reaction between cyclopentadiene and nonyl acrylate.65... 

Much effort has been directed at developing aqueous Diels-Alder reactions toward the syntheses of a variety of complex natural products. Grieco employed micellar catalysis and pure water as the solvent for the Diels-Alder reaction of dienecarboxylate with a variety of dienophiles. For example, when the Diels-Alder reaction in Scheme 12.3 was carried out in water, a higher reaction rate and reversal of the selectivity were observed, compared with the same reaction in a hydrocarbon solvent (Scheme 12.3).81 Similarly, the reaction of 2,6-dimethylbenzoquinone with sodium ( )-3,5-hexadienoate (generated in situ by the addition of 0.95 equiv sodium bicarbonate to a suspension of the precursor acid in water) proceeded for 1 hour to give a 77% yield of the adduct... 

In this chapter we wish to review the collected evidence for the astonishing effects of water on reactivities and selectivities as exemplified by the Diels-Alder reactions of dienes. Examples of Lewis acid and micellar catalysis in aqueous media are also presented. Finally, the newest computational investigations including solvent effects on Diels-Alder reactions are put forward in order to rationalize some of the remarkable observations. 

In subsequent studies it has been found that a combination of Lewis-acid and micellar catalysis can lead to huge (in fact, enzyme like) rate acceleration in water. In the absence of Lewis-acid catalysts, micelles tend to inhibit Diels-Alder reactions, largely because of the particular nature of the substrate binding sites at the micelle. This problem can be solved by adding Lewis-acid catalysts that bind effectively at the micellar surface. 

Micellar catalysis, conducted in the absence of Lewis acid tends to inhibit the Diels-Alder reaction, relative to the reaction in water. The reason is that the local reaction medium in the Stern region is less favorable than bulk water. However, by combining Lewis-acid and micellar catalysis, enzyme-hke rate accelerations can be obtained (Table 7.5) in case the Lewis acid acts as the counterion for the miceUe. " ... 

Lewis-acid catalysis of Diels-Alder reactions involving bidentate dienophiles in water is possible also if the beneficial effect of water on the catalyzed reaction is reduced relative to pure water. There are no additional effects on endo-exo selectivity. As expected, catalysis by Cu ions is much more efficient than specific-acid catalysis.Using a-amino acids as chiral ligands, Lewis-acid enan-tioselectivity is enhanced in water compared to organic solvents. Micelles, in the absence of Lewis acids, are poor catalysts, but combining Lewis-acid catalysis and micellar catalysis leads to a rate accelaration that is enzyme-like. 

Grieco, P. A. Giamer, P. He, Z.-M. "Micellar" catalysis in the aqueous intermolecular Diels-Alder reaction Rate acceleration and enhanced selectivity, Tetrahedron Lett. 1983, 24,1897-1900. 

On the basis of the pronounced non-polar character of the majority of Diels-Alder reactants, efficient micellar catalysis of their reaction might be anticipated. The first time a micellar catalysed Diels-Alder reaction was mentioned, not the micelle itself, but some type of micellar catalysis, resulting in mutual binding of reactants was suggested to be responsible for the observed rate accelerations . Further investigations on the catalytic activity of micelles showed that several species which are able to form micelles in aqueous solution lead to higher yields in intramolecular Diels-Alder reactions . In detailed studies of the effects of /3-cyclodexlrin 12 on the rates of Diels-Alder reactions " it became clear that the infiuence of cyclodextrin micelles can lead either to inhibition or to acceleration (Table 27). 

Another important finding in micellar catalysis is its ability to combine rate acceleration with enhanced selectivities, as shown by Grieco et al. In the case of the Diels-Alder reaction, the authors observed an increased endo/exo ratio in water that was attributed to the enforced relative orientation of the reactants in the micelles, which were formed by the sodium salt of the diene itself (Figure 3). ... 

Another interesting coupled system between Lewis acid and micellar catalysis was developed by Engberts et al. with a million-fold acceleration of the Diels-Alder reaction. It was shown that if in the absence of Lewis acids, the reaction is retarded by micelles of CTAB or SDS—because of the different binding locations between the diene and the dienophile—the addition of copper dodecylsulfate leads to dramatic rate accelerations due to the complexation of the dienophile to the catalytically active copper ions, and to the high local concentration of both species at the micellar surface. ... 

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