Lithium enolates are usually made at low temperature in THF with a hindered lithium amide base (often LDA) and are stable under those conditions because of the strong O–Li bond. The formation of the enolate begins with Li–O bond formation before the removal of the proton from the position by the basic nitrogen atom.

This reaction happens very quickly—so quickly that the partly formed enolate does not have a chance to react with unenolized carbonyl compound before proton removal is complete.

Now, if a second carbonyl compound is added, it too complexes with the same lithium atom. This allows the aldol reaction to take place by a cyclic mechanism in the coordination sphere of the lithium atom. The aldol step itself is now a very favourable intramolecular reaction with a six-membered cyclic transition state. The product is initially the lithium alkoxide of the aldol, which gives the aldol on work-up.

This reaction works well even if the electrophilic partner is an enolizable aldehyde. In this example, an unsymmetrical ketone (blocked on one side by an aromatic ring) reacts as the enol partner in excellent yield with a very enolizable aldehyde. This is the fi rst complete aldol reaction we have shown you using a specifi c enol equivalent: notice the important point that it is done in two steps:

• first, form the specifi c enol equivalent (here, the lithium enolate at low temperature)

 • then add the electrophile.

Contrast the crossed aldols earlier in the chapter, where enolizable component, base, and electrophile were all mixed together in one step. The next example is particularly impressive. The enol partner is a symmetrical ketone that is very hindered—there is only one hydrogen on either side. The electrophilic partner is a conjugated enal that is not enolizable but that might accept the nucleophile in a conjugate manner. In spite of these potential problems, the reaction goes in excellent yield.

You may wonder why we did not mention the stereochemistry of the fi rst of these two products. Two new stereogenic centres are formed and the product is a mixture of diastereo isomers. In fact, both of these products were wanted for oxidation to the 1,3-diketone so the stereochemistry is irrelevant. This sequence shows that the aldol reaction can be used to make diketones too.

مواضيع ذات صلة

The Robinson annelation

Intramolecular aldol reactions

How to control aldol reactions of aldehydes

How to control aldol reactions of esters

Specifi c enol equivalents from 1,3-dicarbonyl compounds

Conjugated Wittig reagents as specific enol equivalents

Silyl enol ethers in aldol reactions

The Mannich reaction

Base-promoted halogenation

Halogenation

Racemization

Thermodynamically stable enols: 1,3-dicarbonyl compounds