Lewis acid catalysis water compatibility

In a second attempt to extend the scope of Lewis-acid catalysis of Diels-Alder reactions in water, we have used the Mannich reaction to convert a ketone-activated monodentate dienophile into a potentially chelating p-amino ketone. The Mannich reaction seemed ideally suited for the purpose of introducing a second coordination site on a temporary basis. This reaction adds a strongly Lewis-basic amino functionality on a position p to the ketone. Moreover, the Mannich reaction is usually a reversible process, which should allow removal of the auxiliary after the reaction. Furthermore, the reaction is compatible with the use of an aqueous medium. Some Mannich reactions have even been reported to benefit from the use of water ". Finally, Lewis-acid catalysis of Mannich-type reactions in mixtures of organic solvents and water has been reported ". Hence, if both addition of the auxiliary and the subsequent Diels-Alder reaction benefit from Lewis-acid catalysis, the possibility arises of merging these steps into a one-pot procedure. 

In this chapter Lewis-acid-mediated reactions have been summarized. While more than stoichiometric amounts of the Lewis acids were employed in conventional reactions, many efforts have been made to reduce the amounts of Lewis acid needed, and many truly catalytic reactions have been developed. Chiral Lewis-acid catalysis has been of great interest in the 1990s and early 2000s, and various combinations of metals and ligands have been investigated. Importantly, the established understanding that Lewis acids are easily hydrolyzed in water has been exploded. Water-compatible Lewis acids are stable in air and moisture, and are easily recovered and reused in many cases. These Lewis acids may solve recent environmental issues, and will be used further in many reactions in future. 

Due to increasing demands for optically active compounds, many catalytic asymmetric reactions have been investigated in this decade. However, asymmetric catalysis in water or water/organic solvent systems is difficult because many chiral catalysts are not stable in the presence of water [19]. In particular, chiral Lewis acid catalysis in aqueous media is extremely difficult because most chiral Lewis acids decompose rapidly in the presence of water [20, 21]. To address this issue, catalytic asymmetric reactions using water-compatible Lewis acids with chiral ligands have been developed [22-29]. 

In the course of our investigations to circumvent the second drawback in the use of water (the decomposition problem), we have found that some metal salts such as rare earth metal triflates (triflate = trifluoromethanesulfonate) can be used as water-compatible Lewis acids [16,17]. Lewis acid catalysis has attracted much attention in organic synthesis [18]. Although various kinds of Lewis acids have been developed and many have been applied in industry, these Lewis acids must be generally used under strictly anhydrous conditions. The presence of even a small amount of water stops the reactions, because most Lewis acids immediately react with water rather than substrates. In addition, recovery and reuse of the conventional Lewis acids are formidable tasks. These disadvantages have restricted the use of Lewis acids in organic synthesis. 

Chiral Lewis acid catalysis in aqueous media is known to be very difficult to attain, because most chiral Lewis acids are not stable in the presence of water, even using water-compatible Lewis acids. A breakthrough in this field has been reported in catalytic asymmetric hydroxymethylation in aqueous media [170]. It was found that a combination of Sc(OTf)3 and ligand (3) worked effectively in the reaction of a commercially available formaldehyde water solution with several types of silyl enol ethers (Scheme 12.74) [171]. 

A variety of detailed chemical mechanisms for the carbonic anhydrase-cata-lyzed hydration of CO2 have been suggested which appear to be compatible with most, if not all, of the available physico-chemical information [see Refs. (30—33) ]. The various roles envisaged for zinc ion include (a) the direct Lewis acid activation of CO 2 via inner sphere coordination, (b) enhancement of the nucleophilicity of the attacking water molecule as a consequence of inner sphere coordination and pKa pertimbation, (c) activation of an outer sphere water molecule for nucleophilic attack via base catalysis involving zinc(II)-hydroxide, and (d) a combination of Lweis acid catalysis and nucleophile activation via penta-coordinate intermediates (or transition-states). In the following paragraphs the relative merits and the plausibility of select examples of these mechanisms are considered. 

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