Robinson Annulation - Reaction Mechanism

Reaction Mechanism

The original procedure of the Robinson annulation begins with the nucleophilic attack of a ketone in a Michael reaction on a vinyl ketone to produce the intermediate Michael adduct. Subsequent aldol type ring closure leads to the keto alcohol, which is then followed by dehydration to produce the annulation product.

In the Michael reaction, the ketone, labeled A in the diagram below, is deprotonated by a base to form an enolate nucleophile which attacks the electron acceptor as we can see in step B. This acceptor is generally an α,β-unsaturated ketone, although aldehydes, acid derivatives and similar compounds can work as well (see scope). The aldol condensation is an intramolecular process that creates the namesake ring of the Robinson annulation product going from step C through to step F.

In order to avoid a reaction between the original enolate and the cyclohexenone product, the initial Michael adduct, labeled C, is often isolated first and then cyclized to give the desired octalone, labeled F, in a separate step.