Robinson Annulation: Definition, Process, Reaction Mechanism and Application

Robinson Annulation is an organic chemistry process that is necessary for ring formation. Sir Robert Robison discovered the technique in 1935, and it is now known as Sir Robert Robison's Process. By forming a six-membered ring, the Robinson annulation process creates three new carbon-carbon bonds. Here, we will be discussing the process, reaction mechanism and application of Robinson Annulation along with a few important questions.

Keyterms: Organic chemistry, Carbon, Carbon-carbon bonds, Annulus, Ketone, Ester, Carbonyls

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What is Robinson Annulation?

A di-carbonyl is frequently formed as a result of a Michael addition, which can then undergo an intramolecular aldol reaction. When these two processes are combined in one reaction, two new carbon-carbon bonds are formed, as well as a ring. An annulation is a ring-forming reaction named after the Latin word annulus, which means ring annulus. The reaction is named after Sir Robert Robinson (1886-1975), an English scientist who invented it. It must be noted that five and six-membered rings are recommended during annulations.

Robinson Annulation

An enolate ion or enamine of a cyclic ketone, β -keto ester, or β -diketone is usually the nucleophilic enolate donor. An, β -unsaturated ketone is commonly used as an electrophilic acceptor. Deprotonation of 2-methyl-1,3-cyclohexanedione to generate an enolate influences a Michael reaction addition on 3-buten-2-one, generating a C-C bond. A 1,5-diketone fragment is present in the product, which can undergo intramolecular aldol condensation. The methyl ketone undergoes an intramolecular aldol reaction, which results in the formation of a new enolate. One of the ring carbonyls forms a new C-C bond, forming a new six-membered ring. The resultant alcohol is then removed in the third stage, leaving α, β-unsaturated ketone as the final Robinson annulation product. The Robinson Annulation requires a complete equivalent of the base because it is an aldol reaction.

Read more: Aldehydes, Ketones and Carboxylic

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Processes Involved during Robinson Annulation

Michael's addition is followed by aldol condensation in Robinson's Annulation.

Michael addition: Michael's addition is when the alpha beta-unsaturated ketones are added. The alpha-beta nitriles and carbon nucleophiles undergo a 1,4-addition process. Enolate is produced as a consequence, and tautomerization follows.

Aldol condensation: It is a reaction that occurs between two carbonyl compounds that are not the same. As a result, crystallization occurs, resulting in the formation of a six-membered cyclic product. Hydrolysis then produces alpha and beta-unsaturated cyclic ketones.

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Robinson Annulation Mechanism

Michael's addition and aldol condensation are significant steps in the Robinson annulation reaction.

• First, the Michael reaction occurs following the aldol condensation in the Robinson annulation mechanism.
• The αβ unsaturated ketone undergoes Michael's addition as the following step in the Robinson annulation reaction process.
• Tautomerization leads to the creation of enolates, which then leads to subsequent reactions.
• The following stage is cyclization. Aldol condensation produces a six-membered cyclic product.
• After hydrolysis, the αβ unsaturated cyclic ketones are finally produced.

Robinson Annulation Mechanism

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Application of Robinson Annulation

Spirocyclic molecules are also synthesized using Robinson annulation. The Robinson Annulation's strengths lay in its applicability in the entire synthesis of complex compounds, and it is still the preferred method for synthesizing naturally occurring steroids, alkaloids, and terpenoids.

The Robinson annulation is at the heart of a slew of syntheses. Those that use the Robinson annulation to create an internal ring are noteworthy. The presence of a functionalized chain at the vinyl ketone's alpha carbon facilitates the synthetic process. Robinson Annulation is an extremely significant six-membered ring synthesis.

Application of Robinson Annulation

As Robinson Annulation is a formal [4+2] condensation reaction, the new rings that result are always six-membered. The definition of Robinson annulations has been expanded to include [3+3] annulations. Robinson annulation is a broad term for all ring-forming cascades involving the Micheal and intramolecular aldol reactions.

Read more: Common Ion Effect

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Conditions for Robinson Annulation

Primary conditions are usually required for the Robinson annulation reaction to occur. The reaction has, however, been carried out under various settings. Heathcock and Ellis experimented with sulfuric acid and related compounds, and their findings were published. Michael's reaction can be carried out in neutral conditions with the help of an enamine. The Michael adduct is made by heating the Mannich base in the presence of a ketone. Various versions of the procedure have been utilized, including the Wichterle reaction, Hauser annulation, and asymmetric Robinson annulation. To achieve the variation, methods such as Dieckmann condensation and catalysts such as proline catalysts have been used frequently.

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Things to Remember

• The Robinson annulation is an organic process in which three new C-C bonds form a ring structure.
• It's quite handy for forming fused ring formations.
• The Robinson annulation is a reaction that combines the Michael reaction and intramolecular aldol condensation, two carbonyl coupling reactions.
• In organocatalysis research, the Robinson annulation provides a model reaction for evaluating enantioselectivity.
• The Robinson annulation product of 2-methylcyclohexane-1,3-dione and methyl vinyl ketone is the Wieland–Miescher ketone.
• Methyl vinyl ketone (or variants thereof) is required for the annulation since they are both a Michael acceptor and an aldol condensation participant.