Asymmetric Catalysis in Aqueous Media

Catalytic asymmetric aldol reactions have emerged as one of the most powerful carbon-carbon bond-forming processes affording synthetically useful, optically active /3-hydroxy carbonyl compounds [36]. Among them, chiral Lewis acid-catalyzed reactions of aldehydes with silyl enol ethers are one of the most promising methods. Although several successful examples have been developed since 1990 [37], most of the reactions have to be conducted at low reaction temperatures (e.g., — 78°C) in aprotic anhydrous solvents such as dry dichloromethane, toluene, and propionitrile. 

While Ln(OTf)3 are the first metal salts which were found to catalyze aldol reactions of aldehydes with silyl enol ethers efficiently in aqueous media, it has been difficult to realize asymmetric versions of Ln(OTf)3-catalyzed reactions in such media. Recently, the first example of this type of reaction using chiral bis-pyridino-18-crown-6 (Structure 4) has been developed (Eq. 8) [38]. In the reaction of benzal-dehyde 5 with water-ethanol (1/9), the cation size of rare earth metal triflates including Ln(OTf)3 strongly affected the diastereo- and enantioselectivities of the 

A study on the reaction profile of the asymmetric aldol reaction catalyzed by Pr(OTf)3 with 4 revealed that his crown ether-type chiral ligand did not significantly reduce the activity of the metal triflates. This retention of the activity even in the presence of the crown ether containing oxygen and nitrogen atoms in a key to realize the asymmetric induction in this asymmetric aldol reaction in aqueous me- 

Lanthanide triflates are stable Lewis acids in water and are successfully used in several carbon-carbon bond-forming reactions in aqueous solutions. The reactions proceed smoothly in the presence of a catalytic amount of the triflate under mild conditions. Moreover, the catalysts can be recovered after the reactions are completed and can be re-used. Lewis acid catalysis in micellar systems will lead to clean and environmentally friendly processes, and it will become a more important topic in the future. Finally, catalytic asymmetric aldol reactions in aqueous media have been attained using Ln(OTf)3-chiral crown ether complex as a catalyst. 

Cordova, J. Am. Chem. Soc. 1982, 104, 555 (b) B. B. Snider, in Selec-tivities in Lewis Acid Promoted Reactions (Ed. D. Schinzer), Kluwer, Dordrecht, 1989, p. 147 (c) K. Maruoka, A. B. Concepcion, N. Hirayama, H. Yamamoto, 

Mesmer, The Hydrolysis of Cations, John Wiley, New York 1976, p. 129. 

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Abstract Several bismuth-catalyzed synthetic reactions, which proceed well in aqueous media, are discussed. Due to increasing demand of water as a solvent in organic synthesis, catalysts that can be used in aqueous media are becoming more and more important. Although bismuth Lewis acids are not very stable in water, it has been revealed that they can be stabilized by basic ligands. Chiral amine and related basic ligands combined with bismuth Lewis acids are particularly useful in asymmetric catalysis in aqueous media. On the other hand, bismuth hydroxide is stable and works as an efficient catalyst for carbon-carbon bond-forming reactions in water. 

I 6 Heterogeneous Asymmetric Catalysis in Aqueous Media Table 6.1 Asymmetric allylic alkylation in water with a chiral polymeric palladium complex. 

Uozomi Y. Heterogeneous asymmetric catalysis in aqueous media. In Ding K, Uozomi Y, editors. Handbook of asymmetric heterogenous catalysis. Weinheim Wiley-VCH 2008 p 209-232. 

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]. 

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]. 

Lewis acids as water-stable catalysts have been developed. Metal salts, such as rare earth metal triflates, can be used in aldol reactions of aldehydes with silyl enolates in aqueous media. These salts can be recovered after the reactions and reused. Furthermore, surfactant-aided Lewis acid catalysis, which can be used for aldol reactions in water without using any organic solvents, has been also developed. These reaction systems have been applied successfully to catalytic asymmetric aldol reactions in aqueous media. In addition, the surfactant-aided Lewis acid catalysis for Mannich-type reactions in water has been disclosed. These investigations are expected to contribute to the decrease of the use of harmful organic solvents in chemical processes, leading to environmentally friendly green chemistry. 

There is very little information available on asymmetric hydroformylation in aqueous solutions or biphasic mixtures despite that asymmetric hydroformylation in organic solvents has long been studied very actively. This is even more surprising since enantioselective hydrogenation in aqueous media has been traditionally a focal point of aqueous organometallic catalysis and several water soluble phosphine ligands have been synthetized in enantiomerically pure form. 

Enzyme-catalyzed asymmetric syntheses involve two types of reactions (1) the asymmetric reduction of a prochiral center and (2) the resolution of a racemic material by selective reaction of one enantiomer. Both types arc demonstrated in the syntheses of chiral insect phermones reviewed by Sonnet (1988). Enzymes that have broad substrate specificity and still retain other selectivity features can be versatile and powerful catalysts. In addition, enzyme catalysis is applicable not only in aqueous media but also in nonaqueous solvents, including supercritical fluids (20-22), In all cases, however, enzymes require water to function as catalysts. A small amount of water, corresponding to a monolayer on the enzyme molecule, is usually sufficient (20),... 

General reviews include the direct aldol/" aldoi and related processes,the Zimmerman-Traxler TS model used to explain the stereochemistry of the aldoi condensation,catalysis of direct asymmetric aldols by prolinamides versus prolinef/zioamides, " " the catalytic asymmetric aldoi reaction in aqueous media (considering both organometallic and organocatalytic approaches), " the use of BINAP oxide in enantioselective direct aldols,and the use of metal enolates as synthons. " ... 

Direct asymmetric aldol reactions in aqueous media catalysed by phenolic proli-namides show enhanced de and ee when the catalysis is augmented by LiCl, ZnClj or 0... 

Corey, E. J. Catalytic Enantioselective Diels-Alder Reactions Methods, Mechanistic Fundamentals, Pathways, and Applications Anptew. Chem. IntEd. 2002, 41, 1560-1567. Fringuelli, F. Piermatti, O. Pizzo, F. Vaccaro, L. Recent Advances in Lewis Acid Catalyzed Diels-Alder Reactions in Aqueous Media Eur. J. Orpj. Chem. 2001, 439-455. Evans, D. A. Johnson, J. S. Diels-Alder Reactions Comprehensive Asymmetric Catalysis 1999, 5, 1177-1235. 

Asymmetric water-soluble ligands are known for the metal-catalyzed hydrocyanation of achiral alkenes. However, neither Jenck [21] or Davis [22] actually provides any examples of hydrocyanation catalysis in these patents so the performance of these mono- and bisphosphines in aqueous and supported aqueous media cannot be assessed although this may be a promising route for the synthesis of biologically active nitrile intermediates and products. 

More common is the general acid- or base-catalyzed addition of HCN to ketones and aldehydes to give cyanohydrins [Eq. (2)] [1]. Because of the propensity of HCN to spontaneously and exothermically polymerize under basic conditions, general acid catalysis is sometimes favored over basic media, as was the case in the recent Sumitomo [3] and Upjohn work [4, 5]. Applications of aqueous media have been reported to lead to asymmetric hydrocyanation catalysis [Eq. (3)] [6, 7]. 

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