2 ’- -catalysed aldol reaction

A probable mechanism of these base-catalysed aldol reactions may be written in gena-al terms as follows ... 

It turned out that the dodecylsulfate surfactants Co(DS)i Ni(DS)2, Cu(DS)2 and Zn(DS)2 containing catalytically active counterions are extremely potent catalysts for the Diels-Alder reaction between 5.1 and 5.2 (see Scheme 5.1). The physical properties of these micelles have been described in the literature and a small number of catalytic studies have been reported. The influence of Cu(DS)2 micelles on the kinetics of quenching of a photoexcited species has been investigated. Interestingly, Kobayashi recently employed surfactants in scandium triflate catalysed aldol reactions". Robinson et al. have demonshuted that the interaction between metal ions and ligand at the surface of dodecylsulfate micelles can be extremely efficient. ... 

Gruttadauria, M., Riela, S., Lo Meo, P., D Anna, F., Noto, R. (2004) Supported Ionic Liquid Asymmetric Catalysis A New Method for Chiral Catalysts Recycling, the Case of ProUne-Catalysed Aldol Reaction. Tetrahedon Letters, 45(32), 6113-6116. 

Au-catalysed aldol reaction with sulfur-containing ferrocenylpho-sphine ligand. 

A series of frani -chelating chiral biferrocene diphosphine ligands enable a rhodium(I)-catalysed aldol reaction of 2-cyanopropionates to proceed in up to 93%... 

The synthesis of epothilone A and C using an antibody catalysed aldol reaction has been reported <98M14603>. The synthesis of 12,13-desoxyepothilone has also been reported <99JA7050>. 

Aldol condensations were originally carried out in the liquid phase and catalysed homogeneously by acids or bases this way of operation is still predominant. Solid-catalysed aldol reactions can also be performed in the liquid phase (in trickle or submerged beds of catalyst), but in many cases vapour phase systems are preferred the factors determining the choice are the boiling points and the stability of the reactants at elevated temperatures. At higher temperatures, the formation of a, j3-unsaturated aldehydes or ketones [reactions (B) and (C)] is preferred to aldol (ketol) formation [reaction (A)]. A side reaction, which may become important in some cases, is the self-condensation of the more reactive carbonyl compound if a mixed condensation of two different aldehydes or ketones is occurring. The Cannizzaro reaction of some aldehydes or polymerisation to polyols or other resin-like products can also accompany the main reaction. 

In the work concerning the mechanism of solid-catalysed aldol reactions, the analogy between the homogeneous and heterogeneous mechanisms is usually assumed [370,372—375]. The mechanism of base-catalysed condensations, which has received much attention (cf. ref. 371), may be pictured in general as... 

The base-catalysed Aldol reaction is shown in Equation 3.11 [3, 4], and a mechanism to account for the global process in Scheme 3.1. At low concentrations of acetaldehyde, reverse of the proton-abstraction steps is fast compared with the forward bimolecular enolate capture (k [CH3CHO] <rate limiting. Under these conditions, the kinetics are second order in [CH3CHO] and show specific base catalysis, i.e. the reaction is first order in [HCY ] and, even though B is involved in the mechanism, it does not appear in the rate law [5]. According to this mechanism, therefore, the overall rate law is given by Equation 3.12 ... 

Scheme 3.1 A mechanism for the base-catalysed Aldol reaction.

More effort was therefore invested in the application of synthetic methodologies for these alkaloids and some straightforward chemo-enzymatic approaches were recently developed [150]. An enzyme-catalysed aldol reaction was again a crucial step in that synthetic route and is strongly reminiscent of Wong s research strategy relating to the chemo-enzymatic synthesis of pyrrolizidines mentioned earlier. 

The elimination is even easier in acid solution and acid-catalysed aldol reactions commonly give unsaturated products instead of aldols. In this simple example with a symmetrical cyclic ketone, the enone is formed in good yield in acid or base. We shall use the acid-catalysed reaction to illustrate the mechanism. First the ketone is enolized under acid catalysis as you saw in Chapter 21. 

Then the aldol reaction takes place. Enols are less nucleophilic than enolates, and the reaction occurs because the electrophilic carbonyl component is protonated the addition is acid-catalysed. An acid-catalysed aldol reaction takes place. 

Base-catalysed aldol reactions may give the aldol product, or may give the V dehydrated enone or enalby an ElcB mechanism... 

Scheme 9.6 Ruthenium catalysed aldol reaction with indium(III) acetate as co-catalyst...

While the Lewis acid-catalysed aldol reactions in water-containing solvents described above were catalysed by several metal salts, a certain amount of organic solvents such as THF and ethanol still had to be combined with water to dissolve organic substrates and promote the reactions efficiently. However, it is desirable to avoid the use of harmful organic solvents. Therefore, we initiated investigations to develop a new system for Lewis acid-catalysed reactions in water without using any organic solvents. 

TABLE 13.2. Effect of solvents on LASC-catalysed aldol reaction. 

Various substrates have been successfully used in the present LASC-catalysed aldol reaction. Aromatic as well as aliphatic, a, 3-unsaturated and heterocyclic aldehydes worked well. As for silicon enolates, silyl enol ethers derived from ketones as well as ketene silyl acetals derived from thioesters and esters reacted well to give the corresponding adducts in high yields. It is noted that highly water-sensitive ketene silyl acetals reacted smoothly in water under these conditions. 

Even greater rates have been achieved in the Yb(OTf)3-catalysed aldol reactions of silylenol ethers with aldehydes in micelles, by adding a small quantity of surfactant, such as sodium dodecyl sulfate. 

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