Aldol reaction in water without organic solvents

4 Aldol reaction in water without organic solvents 

While aldol reactions stated above were smoothly catalyzed by the water-stable Lewis acids in aqueous media, a certain amount of organic solvent such as THF or EtOH had to be still combined with water to promote the reactions efficiently. To avoid the use of the organic solvents, we have developed a new reaction system in which Sc(OTf)3 catalyzes Mukaiyama aldol reactions in pure water without any organic solvents in the presence of a small amount of a surfactant such as sodium dodecyl sulfate (SDS). 

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. 

Several examples of the Sc(OTf)3-catalyzed aldol reactions in micellar systems are shown in Table 14-7. Not only aromatic but also aliphatic and a,/(-unsaturated aldehydes reacted with silyl enol ethers to afford the corresponding aldol adducts in high yields. Formaldehyde/water solution also worked well. Ketene silyl acetal 4, which is known to be hydrolyzed very easily even in the presence of a small amount of water, reacted with an aldehyde in the present micellar system to afford the corresponding aldol adduct in a high yield. 

Furthermore, we have introduced new types of Lewis acids, scandium tris(do-decyl sulfate) (5a) and scandium trisdodecanesulfonate (6a) (Chart 14-1) [36]. 

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