Robinson Annulation: Mechanism and its Applications

Robinson annulation is a type of chemical reaction in which ring formation occurs by combining the Michael reaction and the intramolecular aldol reaction. The word annulation comes from the Greek word β€œannulus” which means ring, whereas the word Robinson comes from the name of the chemist Robert Robinson who discovered the method in 1935. Later in 1947, he was awarded Nobel Prize in chemistry.

Robinson annulation required two starting reactants to initiate the reaction. One is the methyl vinyl ketone (a) that forms 𝛼, 𝛽-unsaturated carbonyl compound while the second reactant is the ketone (b) that forms enolate. The resultant product (c) is the six-membered ring that has three new C-C bonds, two sigma (𝝈) bonds, and one pi (πœ‹) bond.

robinson annulation reaction

To generate the enolate during the Robinson annulation reaction, these bases are used:

  • OHβˆ’ in H2O
  • OEtβˆ’ in EtOH

Robinson Annulation Reaction Mechanism

The reaction mechanism of Robinson’s annulation starts with the Michael reaction, in which a nucleophilic attack of ketone takes place on vinyl ketone to produce an intermediate adduct called Michael adduct. At the same time, the aldol-type ring closes and gives keto alcohol. Then dehydration results in an annulation product.

At the stage of Michael’s reaction in Robinson’s annulation, a base attacks the ketone to form an enolate nucleophile. This nucleophile further attacks the electrophile (𝛼, 𝛽-unsaturated ketone in green color). During the reaction, regioselectivity is controlled by the formation of enolate. It can also be controlled by using the beta-diketone or beta-ketoester instead of enolate.

However, deprotonation is more favorable at the carbon which is attached to the carbonyl group and then aldol condensation takes place in such a manner that adds a six-membered.

robinson annulation reaction mechanism

Stereochemistry in Robinson Annulation

Studies revealed that hydroxy ketones can be formed in the Robinson annulation reaction. In kinetically controlled reactions, trans compounds are more favorable due to the anti-periplanar effect of the aldol condensation. Secondly, it is found that cyclization can be done in synclinal orientation also.

These are the three stereochemical pathways:

stereochemistry of robinson annulation

The formation of the above chair transition states depends on the type of solvent. There can be a difference between the formation of the transition states by the interaction of the solvent. However, changing the type of the solvent gives different results in stereochemistry.

Applications of Robinson Annulation

These are the most important applications of Robinson annulation:

  • Robinson annulation is used in the production of chemicals like spirocyclic compounds.
  • The most important use of Robinson annulation is in the formation of cyclohexenone and its derivatives which has very importance in the field of chemistry.
  • It is used in the synthesis of antibiotics, steroids, and cortisone.
  • Robinson annulation reaction was used to introduce new six-membered rings in the compounds.
  • It is used in the synthesis of Wieland-Miescher ketone which has biological importance.

Concepts Berg

What is Robinson’s annulation reaction?

It is a six-membered ring-forming reaction by combining Michael’s reaction and aldol condensation reaction.

What is the product of a Robinson annulation?

The product of the Robinson annulation reaction is a six-membered ring.

What two reactions are involved in Robinson’s annulation?

These are the two reactions involved in the Robinson annulation reaction:

  • Michael reaction
  • Aldol condensation reaction

Can the Robinson annulation be done under acidic conditions?

Robinson’s annulation reaction required a base-catalyzed reaction.

Reference

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