Ionic water aldol reaction

Aqueous base (e.g., NaOH or basic ion-exchange resin) has been used for Aldol reactions. In this case, the performance of the ionic liquids containing 1 mol% NaOH was compared with that of water with the same NaOH content. In the Aldol... 

In the (S)-proline-catalyzed aldol reactions, the addition of a small amount of water did not affect the stereoselectivities [6]. However, a large amount of water often resulted in products with low enantiomeric excess water molecules interrupt the hydrogen bonds and ionic interactions critical for the transition states that lead to the high stereocontrol. For example, in the (S)-proline-catalyzed aldol reaction of acetone and 4-nitrobenzaldehyde in DMSO, the addition of 10% (v/v) water to the reaction mixture reduced the ee-value from 76% (no water) to 30% [6]. Note that the addition of a small amount of water into (S)-proline-catalyzed reactions often accelerates the reaction rate, and the addition of water should be investigated when optimizing these reactions [61]. 

The surfactant-aided Lewis acid catalysis was first demonstrated in the model reaction shown in Table 13.1 [22]. While the reaction proceeded sluggishly in the presence of 10 mol% scandimn triflate (ScfOTOs) in water, a remarkable enhancement of the reactivity was observed when the reaction was carried out in the presence of 10 mol% Sc(OTf)3 in an aqueous solution of sodium dodecyl sulfate (SDS, 20 mol%, 35 mM), and the corresponding aldol adduct was obtained in high yield. It was found that the type of surfactant influenced the yield, and that Triton X-100, a non-ionic surfactant, was also effective in the aldol reaction (but required longer reaction time), while only a trace amount of the adduct was detected when using a representative cationic surfactant, cetyltrimethylammonium bromide (CTAB). The effectiveness of the anionic surfactant is attributed to high local concentration of scandium cation on the surfaces of dispersed organic phases, which are surroimded by the surfactant molecules. 

Zlotin et al. demonstrated that the asymmetric aldol reaction between aldehydes and ketones could be catalysed by novel chiral ionic liquids bearing a 4-hydroxyproline moiety and pyridinium cation in water. The use of the catalyst with the readily regenerated anion PFe allowed the aldol products to be obtained in excellent stereoselectivities and yields, as shown in Scheme 2.7. 

D. E. Siyutkin, A.S. Kucherenko, M.l. Struchkova, S.G. Zlotin, Anovel (S)-proline-modified task-specific chiral ionic liquid - an amphiphilic recoverable catalyst for direct as)fmmetric aldol reactions in water. Tetrahedron Lett. 49 (2008) 1212-1216. 

BF4] or [bmim][PF6] (Scheme 22.8). Bis-amide 19-catalyzed aldol reactions performed in [bmimllBFJ required a much lower excess of donor ketone 21 (3 equiv. instead of 30 equiv. in proline-catalyzed reactions) and allowed a synthesis of chiral compounds 22 bearing heterocyclic, prenyl, or metallocene units [43], The improved catalytic performance of prolinamide derivatives in ionic liquids might be due to a stabihzation of the iminium intermediate formed from the ketone and the catalyst or because of the enhanced nucleophilicity of the enamine [42]. Notably, IL dilution with water (1 1 by volume) accelerated the enamine/iminium ion hydrolysis and raised reaction rates and product yields, with the enantioselec-tivity being retained or even becoming somewhat higher than under water-free conditions [45], Furthermore, the catalyst/lL/water system could be easily recycled five times without aldol yield, dr, and ee losses. 

Zlotin et al. synthesized the new amphiphihc (S)-proline-modified task-specific chiral ionic liquid 41, bearing hydrophobic anions for asymmetric aldol reactions in water (Scheme 8.17). This hexafluorophosphate salt gave a suspension in water, and high yields and diastereo- and enantioselectivities were observed for the reaction of cyclohexanone with aryl aldehydes. This catalyst could be recycled easily, and retained its activity and selectivity over at least five reaction cycles [43]. A similar type of catalyst was reported by Trombini et al. [44] for carrying out highly enantioselective aldol reactions in water. High enantioselectivities and... 

II reaction under similar conditions at temperatures between 80 and 100°C and with a four-fold excess of 2-methylpentanal (to compensate for the low solubility), the selectivity for the Aldol II product (80%) was 20% higher in [BMIMJEF NaOH than in the water/NaOH system, both at 100% propanal conversion. The increased selectivity was attributed to the higher solubility of the reactant 2-methylpentanal in the ionic liquid phase than in the water phase. The higher solubility of 2-methylpentanal effectively suppressed the self-aldol condensation in the ionic liquid. 

In this initial step, an aldol condensation takes place. The solvent of this reaction is an ionic liquid. It is a very polar solvent that is able to stabilize polar molecules and can act as an acceptor for hydrogen bonds. Thus, it is able to shift the equilibrium towards the enol tautomers. After the aldol addition, the intermediate can eliminate water via a second enol intermediate. Although the substrates are both aldehydes, only one product is formed because 19 lacks an acidic position, so it cannot become a nucleophile. Owing to its tendency to form homodimers, a two-fold excess of propionaldehyde 20 is needed. 

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