Although these are the oldest of the specifi c enol equivalents, they are still widely used because they need no special conditions—no low temperatures or strictly anhydrous solvents. The two most important are derived from malonic acid and ethyl acetoacetate.

Ethyl acetoacetate is partly enolized under normal conditions. So, you might ask, why doesn’t it immediately react with itself by the aldol reaction? There are two aspects to the answer. First, the enol is very stable and, second, the carbonyl groups in the unenolized fraction of the sample are poorly electrophilic ester and ketone groups. The second carbonyl group of the enol is not electrophilic because of conjugation. When a normal carbonyl compound is treated with catalytic acid or base, we have a small proportion of reactive enol or enolate in the presence of large amounts of unenolized electrophile. Aldol reaction (self-condensation) occurs. With 1,3-dicarbonyl compounds we have a small proportion of not particularly reactive unenolized compound in the presence of large amounts of stable (and hence unreactive) enol. No aldol occurs. If we want a crossed aldol reaction with a 1,3-dicarbonyl compound, we simply add a second, electrophilic carbonyl compound such as an aldehyde, along with a weak acid or base. Often a mixture of a secondary amine and a carboxylic acid is used.

Reaction no doubt occurs via the enolate ion generated by the amine while the carboxylic acid buffers the solution, neutralizing the product and preventing enolization of the aldehyde. The amine (pKa R2NH2 + about 10) is a strong enough base to form a significant concentration of enolate from the 1,3-dicarbonyl compound (pKa about 13) but not strong enough to form the enolate from the aldehyde (pKa about 20). The formation of the enolate can be drawn from either tautomer of the malonate.

Now the enolate ion can attack the aldehyde in the usual way, and the buffer action of the acid produces the aldol product in the reaction mixture.

There is still one proton between the two carbonyl groups so enolate anion formation is again easy and dehydration follows to give the unsaturated product.

You may not want a product with both ester groups present, There is a simpler route with the aldol reaction. If, instead of the malonate diester, malonic acid is used, the decarboxylation occurs spontaneously during the reaction. The catalysts this time are usually a more basic mixture of piperidine and pyridine.

The reaction presumably uses the enolate anion of the monocarboxylate anion of malonic acid. Although this enolate is a dianion, its extensive delocalization and the intramolecular hydrogen bond make it really quite stable.

Next comes the aldol step. The dianion attacks the aldehyde, and after proton exchange the aldol is formed (still as the monocarboxylate in this basic solution).

Next comes the aldol step. The dianion attacks the aldehyde, and after proton exchange the aldol is formed (still as the monocarboxylate in this basic solution).

Finally comes the decarboxylation step, which can occur though a cyclic. The decarboxylation could give either an E or a Z double bond depending on which acid group is lost as CO₂, but the transition state lead ing to the more stable E product must be lower in energy since the product has E geometry.

In the first part of this chapter we have looked at general solutions to the problem of control ling crossed aldol reactions. We’ll now turn to the detailed ways those solutions are used with different classes of enolizable compounds.

مواضيع ذات صلة

The Robinson annelation

Intramolecular aldol reactions

How to control aldol reactions of aldehydes

How to control aldol reactions of esters

Conjugated Wittig reagents as specific enol equivalents

Silyl enol ethers in aldol reactions

Lithium enolates in aldol reactions

The Mannich reaction

Base-promoted halogenation

Halogenation

Racemization

Thermodynamically stable enols: 1,3-dicarbonyl compounds