Acid Catalysis in Water

In addition to these advantages, there are several synthetic uses of water as a solvent. First, simple operation systems can be attained by the use of water. That is, workup procedures can be simplified because many organic compounds are lipophilic and may be separated easily from the aqueous phase. Second, control of reaction temperature is easier because the heat capacity of water is extremely high compared with those of most organic solvents. Third, the need for protective groups is reduced in water as amino acids, carbohydrates, and other water-soluble materials can be used as they are. Finally, the unique solvent effects of water are expected to influence the course of many reactions in water. 

In this chapter, we focus on acid catalysis in water. While there are numerous examples of catalytic reactions in water, the main body of these involves acid catalysis. Homogeneous catalysis, heterogeneous catalysis, and micellar catalysis, including catalytic enantioselective reactions, are discussed in detail. Acid-catalyzed reactions using a small amount of water may not be included unless they are crucial for the further development of the field. 

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The second important influence of the solvent on Lewis acid - Lewis base equilibria concerns the interactions with the Lewis base. Consequently the Lewis addity and, for hard Lewis bases, especially the hydrogen bond donor capacity of tire solvent are important parameters. The electron pair acceptor capacities, quantified by the acceptor number AN, together with the hydrogen bond donor addities. O, of some selected solvents are listed in Table 1.5. Water is among the solvents with the highest AN and, accordingly, interacts strongly witli Lewis bases. This seriously hampers die efficiency of Lewis-acid catalysis in water. 

Towards Enantioselective Lewis-Acid Catalysis in Water ... 

Giovanni Boocaletti is gratefully acknowledged for the large number of experiments that paved the way to enantioselective Lewis-acid catalysis in water. Furthermore, we kindly thank the Syncom company for the use of the chiral HPLC column. 

The merits of (enantioselective) Lewis-acid catalysis of Diels-Alder reactions in aqueous solution have been highlighted in Chapters 2 and 3. Both chapters focused on the Diels-Alder reaction of substituted 3-phenyl-1-(2-pyr idyl)-2-prop ene-1-one dienophiles. In this chapter the scope of Lewis-acid catalysis of Diels-Alder reactions in water is investigated. Some literature claims in this area are critically examined and requirements for ejfective Lewis-acid catalysis are formulated. Finally an attempt is made to extend the scope of Lewis-acid catalysis in water by making use of a strongly coordinating auxiliary. 

In summary, the groups of Espenson and Loh observe catalysis of Diels-Alder reactions involving monodentate reactants by Lewis acids in water. If their observations reflect Lewis-acid catalysis, involvirg coordination and concomitant activation of the dienophile, we would conclude that Lewis-acid catalysis in water need not suffer from a limitation to chelating reactants. This conclusion contradicts our observations which have invariably stressed the importance of a chelating potential of the dienophile. Hence it was decided to investigate the effect of indium trichloride and methylrhenium trioxide under homogeneous conditions. 

I owe a lot to Federica Bertondn and Giovanni Boccaletti. During their stay as Erasmus students in Groningen they brought a little bit of Italy with them (I remember some very good meals). Also from a chemical point of view their stays were successful. The compounds prepared and purified by Federica are at the basis of the work described in this thesis. The work of Giovanni has paved the way to enantioselective Lewis-acid catalysis in water, which is perhaps the most significant result of this thesis. 

Judging from these findings, the mechanism of Lewis acid catalysis in water (for example, aldol reactions of aldehydes with silyl enol ethers) can be assumed to be as follows. When metal compounds are added to water, the metals dissodate and hydration occurs immediatdy. At this stage, the intramolecular and intermolecular exchange reactions of water molecules frequently occur. If an aldehyde exists in the system, there is a chance that it will coordinate to the metal cations instead of the water molecules and the aldehyde is then activated. A silyl enol ether attacks this adivated aldehyde to produce the aldol adduct. According to this mechanism, it is expected that many Lewis acid-catalyzed reactions should be successful in aqueous solutions. Although the precise activity as Lewis acids in aqueous media cannot be predicted quantitatively... 

The second important solvent effect on Lewis acid-Lewis base equilibria concerns the interactions with the Lewis base. Since water is also a good electron-pair acceptor129, Lewis-type interactions are competitive. This often seriously hampers the efficiency of Lewis acid catalysis in water. Thirdly, the intermolecular association of a solvent affects the Lewis acid-base equilibrium242. Upon complexation, one or more solvent molecules that were initially coordinated to the Lewis acid or the Lewis base are liberated into the bulk liquid phase, which is an entropically favourable process. This effect is more pronounced in aprotic than in protic solvents which usually have higher cohesive energy densities. The unfavourable entropy changes in protic solvents are somewhat counterbalanced by the formation of new hydrogen bonds in the bulk liquid. 

In summary, water appears as an extremely unsuitable solvent for coordination of hard Lewis acids to hard Lewis bases, as it strongly solvates both species and hinders their interaction. Hence, catalysis of Diels-Alder reactions in water is expected to be difficult due to the relative inefficiency of the interactions between the Diels-Alder reactants and the Lewis acid catalyst. On the other hand, the high stereoselectivities and yields observed in biosyntheses, with water as the solvent, indicate that these rationalizations cannot entirely be true. As a matter of fact, we will demonstrate in the following that Lewis acid catalysis in water is not only possible, but also allows for effective as well as environmentally friendly reaction conditions. 

Aluminium montmorilIonite and rhodium carbonyl have been reported as catalysts for the aldol reaction of enol silanes with aldehydes, but in neither case are the stereoselectives at all high. The reaction has also been found to occur without Lewis acid catalysis in water or in 1 1 water oxolane. Although the yields are not high, the method is of interest in that syn-products were... 

Gu, W., Zhou, W.-J. and Gin, D.L., A nanostructured, scandium-containing polymer for heterogeneous Lewis acid catalysis in water, Chem. Mater., 2001, 13, 1949-1951. 

Ogawa C, Kobayashi S. Acid catalysis in water. In Lindstrom UM, editor. Organic reactions in water principles, strategies and applications. Oxforf, UK Blackwell Publishing Ltd 2007. p. 65. 

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