Aldol reactions micellar systems

Aldol and Mannich-type reactions. Micellar systems favor aldol reactions and... 

Sc(OTf)3-catalyzed aldol reactions have been successfully performed in micellar systems (Scheme 15).59 The catalyst activity is remarkably enhanced by adding a small amount of a surfactant. Allylation60 and Mannich-type reactions61 also proceed smoothly in water in the presence of a catalytic amount of Sc(OTf)3 and a surfactant. 

Table 4. Sc(OTf)3-catalyzed aldol reactions in micellar systems.

Several examples of Sc(OTf)3-catalyzed aldol reactions in micellar systems are shown in Table 4. Not only aromatic, but also aliphatic and a,j8-unsaturated aldehydes react with silyl enol ethers to afford the corresponding aldol adducts in high yields. Aqueous formaldehyde solution also worked well. Even the ketene silyl acetals, which readily hydrolyze in the presence of a small amount of water, reacted with aldehydes... 

S. Kobayashi, T. Wakabayashi, S. Nagayama, H. Oyamada, Tetrahedron Lett. 1997,38,4559-4562. Judging from the amount of the surfactant used in the present case, the aldol reaction would not proceed only in micelles, (a) J. H. Fendler, E. J. Fendler, Catalysis in Micellar and Macromolecular Systems, Academic, London, 1975. (b) Mixed Surfactant Systems (Eds. P. M. Holland, D. N. Rubingh), ACS, Washington, DC, 19W. (c) Structure and Reactivity in Aqueous Solution (Eds. C. J. Cramer, D. G. Truhlar), ACS, Washington, DC, 1994. (d) Surfactant-Enhanced Subsurface Remediation (Eds. D. A. Sabatini, R. C. Knox, J. H. Harwell), ACS, Washington, DC, 1994. 

Lewis acid catalysis in micellar systems [33] was first found in the model reaction in Table 14-6 [34]. While the reaction proceeded sluggishly in the presence of 0.2 eq. Yb(OTf)3 in water, remarkable enhancement of the reactivity was observed when the reaction was carried out in the presence of 0.2 eq. Yb(OTf)3 in an aqueous solution of sodium dodecyl sulfate (SDS, 0.2 eq., 35 mM), and the corresponding aldol adduct was obtained in 50% yield. In the absence of the Lewis acid and the surfactant (water-promoted conditions), only 20% yield of the aldol adduct was isolated after 48 h, while 33% yield of the aldol adduct was obtained after 48 h in the absence of the Lewis acid in an aqueous solution of SDS. The amount of the surfactant also influenced the reactivity, and the yield was improved when Sc(OTf)3 was used as a Lewis acid catalyst. Judging from the critical micelle concentration, micelles would be formed in these reactions, and it is noteworthy that the Lewis acid-catalyzed reactions proceeded smoothly in micellar systems [35]. It was also found that the surfactants influenced the yield, and that Triton X-100 was effective in the aldol reaction (but required long reaction time), while only a trace amount of the adduct was detected when using cetyltri-methylammonium bromide (CTAB) as a surfactant. 

Loh et al. reported that InClj worked as an effective catalyst of aldol reactions of SEE in water [77]. Later, Kobayashi et al. reported different results [78] - hydrolysis of SEE is faster than the desired reaction in the InCls-catalyzed aqueous system the InCls-catalyzed reaction proceeds to some extent under solvent-free conditions InCls is an effective catalyst in micellar systems. 

Quite recently, it has been found that scandium triflate (Sc(OTf)rcatalyzed aldol reactions of silyl enol ethers with aldehydes can be successfully carried out in micellar systems [24], While the reactions proceeded sluggishly in pure water (without organic solvents), remarkable enhancement of the reactivity was observed in the presence of a small amount of a surfactant (cf. Section 4.5). 

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. 

Scandium triflate-catalyzed aldol reactions of silyl enol ethers with aldehyde were successfully carried out in micellar systems and encapsulating systems. While the reactions proceeded sluggishly in water alone, strong enhancement of the reactivity was observed in the presence of a small amount of a surfactant. The effect of surfactant was attributed to the stabiMzation of enol silyl ether by it. Versatile carbon-carbon bondforming reactions proceeded in water without using any organic solvents. Cross-linked Sc-containing dendrimers were also found to be effective and the catalyst can be readily recycled without any appreciable loss of catalytic activity.Aldol reaction of 1-phenyl-l-(trimethylsilyloxy) ethylene and benzaldehyde was also conducted in a gel medium of fluoroalkyl end-capped 2-acrylamido-2-methylpropanesulfonic acid polymer. A nanostmctured, polymer-supported Sc(III) catalyst (NP-Sc) functions in water at ambient temperature and can be efficiently recycled. It also affords stereoselectivities different from isotropic solution and solid-state scandium catalysts in Mukaiyama aldol and Mannich-type reactions. 

The Sc(OTf)3-catalyzed aldol-type reactions of silyl enol ethers with aldehydes can be performed in micellar systems using a catalytic amount of a surfactant such as sodium dodecylsulfate (SDS). In these systems, reactions proceed smoothly in water without using any organic solvent. 

In an early stage of developing organic reactions in aqueous systems, rare earth triflates were used for aldol reactions in THF-water or ethanol-water, giving successful results. On the other hand, when the reactions were carried out in pure water, the corresponding aldol products were obtained only in low yields. " This was probably because solubility of organic substrates was low and decomposition of silyl enol ethers occurred faster than the desired aldol reactions in water. To address this issue, micellar catalysis in water was... 

As mentioned in the previous section, lanthanide and scandium triflates (Ln(OTf)3 and Sc(OTf)3) are stable Lewis acids in water, and aldol reactions of silyl enol ethers with aldehydes proceed smoothly in aqueous media in the presence of a catalytic amount of the lanthanide salt. While the reactions were successfully carried out in THF-water or toluene-ethanol-water, lower yields were obtained in pure water. In the course of our investigations to develop new synthetic reactions, especially carbon-carbon bond-forming reactions, in aqueous media, we have found that such reactions proceeded smoothly in micellar systems. 

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