Dielsalder Reactions In Water

In this chapter we will focus our attention first on Diels-Alder reactions in aqueous solutions: much to the surprise of many chemists, it has been found that

Methods and Reagents for Green Chemistry: An Introduction, Edited by Pietro Tundo, Alvise Perosa, and Fulvio Zecchini

Copyright © 2007 John Wiley & Sons, Inc.

Diels-Alder reactions and other types of cycloadditions are often greatly accelerated in water compared to organic solvents. Also the preferred stereochemistry (i.e., endo/exo ratio) of these reactions is greatly affected in aqueous media. In synthetic organic chemistry, advantage has been taken of this finding. Recent studies have been aimed at identifying the reasons for the rate enhancements and improved stereochemistry. The problem has been settled only recently. Ongoing research is focused on obtaining further understanding of organic reactivity in water.

Then we briefly examine Lewis-acid catalysis of Diels-Alder reactions in water: Lewis-acid catalysis is a valuable alternative for acid catalysis in organic chemistry and biochemistry. The Lewis-acid catalysts are usually polyvalent cations that bind to polar moieties in organic substances, thereby avoiding high Gibbs energy intermediates during the activation process for the particular transformation. In water these binding processes are in competition with hydration of the cations, usually resulting in weak (or no) binding and inefficient catalysis. However, in case of specially designed substrates, extremely efficient catalysis can be achieved.

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.

The Diels-Alder reaction (Figure 7.1) is of great value in synthetic organic chemistry. It is a [4 + 2] cycloaddition in which a diene (4-p component) reacts with a dienophile (2-p component) to provide a six-membered ring. In the reaction six new stereocenters are formed in a single step. The reaction is stereospeci-fic and the absolute configuration of the newly formed asymmetric centers can be controlled efficiently.

Traditionally, the Diels -Alder reaction is performed in organic solvents.

In the one-step symmetry-allowed mechanism, with little charge separation in the activated complex, the Hammett p-values for p-XC6H4- substituted substrates are very small. As anticipated, the reaction has a negative volume of activation.

Quite generally, kinetic solvent effects on the Diels-Alder reaction are small, and, in fact, the small solvent effects have been taken as evidence for minor charge separation during the activation process, consistent with a concerted mechanism.

The first kinetic study of acceleration of some Diels-Alder3-7 reactions in water by Breslow et al. has set the stage for worldwide interest in organic s,

Figure 7.1 Classic mechanism of a Diels-Alder reaction.

TABLE 7.1 Acceleration of Some Diels-Alder Reactions in Water

TABLE 7.1 Acceleration of Some Diels-Alder Reactions in Water

Diels Alder Problem Sets
Source: Refs. 3, 5, and 7.

reactions in water. Some of the results obtained in our laboratory are shown in Table 7.1. It is clear that the aqueous rate accelerations strongly depend on the nature of the diene and the dienophile.

Apart from the aqueous rate accelerations, the aqueous medium has also a favorable effect on the endo-exo selectivity. Substantially higher preferences for the endo isomer were found. This effect can be explained taking the more efficient secondary orbital interactions into considerations as well as additional o


Exo stabilization of the endo transition state, because it is more polar and has a smaller contact area with water.3

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  • karen
    Why is deilsalder reaction in water green?
    8 years ago
    How is the diels alder reaction green chemistry?
    7 years ago
  • danielle
    What is the dies alder reaction in green chemistry?
    7 years ago
  • folcard
    What is a green chemistry advantage of diels alder reaction?
    7 years ago

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