One of the most important applications of the intramolecular aldol reaction is a ring synthesis (annelation or annulation) that takes place in two steps, both involving enols. The compound made by Robinson in the first example is a bicyclic diketone that contains the basic structure of rings A and B of the steroids. The bonds made in the two steps are marked.

Only a weak base is needed to form the stable enolate of the 1,3-diketone and this does conjugate addition onto the enone. The intermediate triketone may be isolated but often isn’t.

The second stage starts with the intramolecular aldol reaction. You should be able to see that the alternatives to a six-membered ring are a four-membered ring and bridged products. The hydroxy-ketone, which happens to have the cis stereochemistry, can also be isolated but eliminates by the E1cB mechanism to complete the aldol sequence

Other ways to carry out this same reaction are to use a secondary amine as the weak base. This gives an excellent yield of the hydroxyketone that can be converted into the enone with acid.

In this sequence the new ring is built onto the side of an old ring but this is not necessary. Any combination of an easily enolizable compound and an enone may give a Robinson annelation product. A simple example combines a non-enolizable enone with ethyl aceto acetate to give an excellent yield of a cyclohexenone. As these compounds are so robust a stronger base can be used.

مواضيع ذات صلة

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

Lithium enolates in aldol reactions

The Mannich reaction

Base-promoted halogenation

Halogenation

Racemization

Thermodynamically stable enols: 1,3-dicarbonyl compounds