Water formation aldol reaction

In the MPVO reaction, several side-reactions can occur (Scheme 20.23). For example, an aldol reaction can occur between two molecules of acetone, which then leads to the formation of diacetone alcohol. The latter acts as a good ligand for the metal of the MPVO catalyst, rendering it inactive. Moreover, the aldol product may subsequently eliminate water, which hydrolyzes the catalyst. The aldol reaction can be suppressed by adding zeolite NaA [84, 92]. 

Komoto detected lactic acid in the mixture from reaction of D-glucose with ammonia,4 and presumed that it was produced from pyruvaldehyde formed by decomposition of D-glucose. Lactic acid has, indeed, been found as a product of the action of alkali (lime-water) on substituted D-glucose and substituted D-fructose,81,83,96 and the mechanism of its formation involves the reversible aldol reaction, followed by formation of pyruvaldehyde, and the benzilic acid rearrangement already described for saccharinic acid this is illustrated83,96 in Scheme 11. 

An aldol reaction of a trimethoxysilyl enol ether, catalysed by a lithium binaphtholate, shows anti diastereoselectivity and modest ees under dry conditions, but addition of water brings about syn adduct formation, with higher ee.131... 

We have already met this in the formation of 16 by dehydration and in the formation of 37 by stable enolate formation. A couple more examples should make the general strategy clear. The unsymmetrical ketone 110 can form an enolate on either side and at first it seems that we shall need a specific enolate to control the aldol reaction. But one product 109 cannot eliminate water while the other 111 can. Under equilibrating conditions 112 is the only product.22... 

The main class of electrophiles which reacts on the sulfur atom of enethiolates are alkyl halides. This was applied by Vallee and Tchertchian [121] in a one pot synthesis of hydroxy-ketenedithioacetals which elegantly uses the preceding features. Deprotonation of alkyl dithioacetates by LDA at -78 °C provided enethiolates which were treated by aldehydes. Comparable to the case of enolates, the aldol reaction takes place on the carbon atom. When water is added to the reaction mixture, 3-hydroxyalkanedithioates are obtained. However, if the quench is replaced by an alkyl halide addition, hydroxyketenedithioacetals are obtained. Formation of these compounds... 

Another control experiment was done to determine the importance of water in this oxidative cleavage reaction. Water was found to be a necessary reagent for the reaction to occur since no p-hydroxybenzaldehyde was obtained when the sodium salt of chlorostilbene 5b was heated in neat nitrobenzene with or without solid sodium hydroxide and a crown ether phase transfer catalyst. Another set of controls was done to evaluate the formation of p-hydroxybenzaldehyde by a nonoxidative reaction, such as the loss of X-PI1-CH2 in a retrograde-type Aldol reaction. No p-hydroxybenzaldehyde was formed when the chlorostilbene 5b was heated at 155 °C for 5 hours in the presence of 2N NaOH but without the presence of nitrobenzene and atmospheric oxygen. Finally, in all of the above control experiments, no oxidized cleavage products were observed from the nonphenolic side of the alcohols 4 or stilbenes 5 (Dershem, S. M., et al., Holzforschung, in press). 

The following example is an intramolecular reaction similar to the aldol reaction. A deprotonated nitrile (nitrile enolate) acts as a nucleophile and adds via an AdN to another nitrile. The acidic water workup is the reverse of imine formation. Section 10.5.2. 

Mukaiyama aldol reactions using a catalytic amount of a Lewis acidic metal salt afford silylated aldols (silyl ethers) as major products, but not free aldols (alcohols). Three mechanistic pathways which account for the formation of the silylated aldols are illustrated in Scheme 10.14. In a metal-catalyzed process the Lewis acidic metal catalyst is regenerated on silylation of the metal aldolate by intramolecular or intermolecular silicon transfer (paths a and b, respectively). If aldolate silylation is slow, a silicon-catalyzed process (path c) might effectively compete with the metal-catalyzed process. Carreira and Bosnich have concluded that some metal triflates serve as precursors of silyl triflates, which promote the aldol reaction as the actual catalysts, as shown in path c [46, 47]. Three similar pathways are possible in the triarylcarbenium ion-catalyzed reaction. According to Denmark et al. triarylcarbenium ions are the actual catalysts (path b) [48], whereas Bosnich has insisted that hydrolysis of the salts by a trace amount of water generates the silicon-based Lewis acids working as the actual catalysts (path c) [47]. Otera et al. have reported that 10-methylacridinium perchlorate is an efficient catalyst of the aldol reaction of ketene triethylsilyl acetals [49]. In this reaction, the perchlorate reacts smoothly with the acetals to produce the actual catalyst, triethylsilyl perchlorate. 

The use of water in Mannich reactions is counterintuitive since it is supposed to shift to the left the imine formation reaction. However, as in the case of aldol reactions catalysed by species 3-12 (Table 1.1), the success is due to the biphasic heterogeneous conditions adopted - all three components of the Mannich reaction and the catalyst forming an organic phase where the process takes place, the water/organic interphase providing a local environment rich in free OH bonds that can co-activate the substrate. ... 

The catalysts used in alcohol synthesis hold the key to selectivity for methanol, for higher oxygenates, and to the control of hydrocarbon formation. Of interest are the mechanisms and the structure-function relationships in the catalysis of the C-H bond formation in reactions (1) and (2), C-C bond formation in reaction (5), and C-O bond formation in reactions (4), (6) and (7), as well as of reactions utilizing the synthesis intermediates as building blocks for organic syntheses such as amine (refs. 9-11) and aldol (refs. 12-14) syntheses. Further, the mechanistic roles of CO2 and water are of importance to understanding the... 

For aldol reactions carried out under catalytic conditions, dehydration of the initial aldol may provide an additional driving force, due to formation of water (with two strong O—H bonds) and the enone system. Such reactions are almost always thermodynamically favorable. 

Now we are prepared to illustrate these experimental protocols of reaction progress kinetic analysis using data from reaction calorimetric monitoring of the aldol reaction shown in Scheme 27.1. We turn hrst to the issue of catalyst stability using our same excess protocol. In these aldol reactions, it was noted that the active catalyst concentration can be effectively decreased by the formation of oxazolidinones between proline and aldehydes or ketones, and that addition of water can suppress this catalyst deactivation. Same excess reactions carried out in the absence of water and in the presence of water are shown in Figure 27.3a and Figure 27.3b, respectively. The plots do not overlay in the absence of water, but they do when water is present. The overlay in these same [e] experiments in Figure 27.3b means that the total concentration of active catalyst within the cycle is constant and is the same in the two experiments where water is present. 

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