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15.38 : Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation

Robinson annulation involves the formation of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors and α,β-unsaturated carbonyl acceptors using a base.

The reaction produces a six-membered ring with three new C–C bonds.

The two-step reaction comprises Michael addition followed by intramolecular aldol condensation.

Michael addition initiates with a base deprotonating the acidic hydrogen in the Michael donor to generate an enolate ion.

Conjugate addition of the enolate to the Michael acceptor, followed by protonation, forms the Michael adduct, which further endures an intramolecular aldol condensation pathway.

Deprotonation of a suitable α hydrogen yields another enolate ion which intramolecularly adds to the carbonyl carbon resulting in a cyclic alkoxy intermediate.

A subsequent protonation, followed by dehydration, gives the annulated product.

To conclude, in Robinson annulation, the α carbon of the donor bonds to the β carbon of the acceptor via Michael addition, and a six-membered ring forms via an intramolecular aldol condensation with a double bond at the position of the ring closure.

Robinson annulation is a base-catalyzed reaction for the synthesis of 2-cyclohexenone derivatives from 1,3-dicarbonyl donors (such as cyclic diketones, β-ketoesters, or β-diketones) and α,β-unsaturated carbonyl acceptors. Named after Sir Robert Robinson, who discovered it, this reaction yields a six-membered ring with three new C–C bonds (two σ bonds and one π bond).

The ring-forming reaction occurs in two stages: Michael addition and the subsequent intramolecular aldol condensation. The reaction commences with the deprotonation of the acidic hydrogen in the donor, generating an enolate ion.

The α,β-unsaturated compound undergoes nucleophilic attack by the enolate via Michael addition, forming an anionic species that gives the Michael adduct upon protonation.

Consequently, the base abstracts an appropriate α proton from the adduct, forming an enolate ion. It undergoes an intramolecular aldol condensation via attack at the carbonyl carbon, forming a cyclic alkoxy intermediate. Finally, protonation of the alkoxy ion and subsequent dehydration gives the annulated product.

Tags

Robinson Annulation Cyclohexenones Michael Addition Aldol Condensation 1 3 dicarbonyl Donors Enolate Ion Nucleophilic Attack Michael Adduct Cyclic Alkoxy Intermediate Annulated Product

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