Tandem Michael + aldol
Robinson annulation: building a ring in two steps
How the Robinson annulation works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: Ketone + methyl vinyl ketone (MVK); NaOEt or KOH. Conditions: EtOH, 25–80 °C; heat for dehydration. Bonds formed: C–C (Michael), C–C (aldol), C=C; bonds broken: α C–H (×2), C=C of MVK, C–OH. Stereochemistry: Quaternary stereocentre; often racemic (proline gives ee). Rate and selectivity: Michael first, then intramolecular aldol; E1cB dehydration last.
At a glance
Step 1: Michael addition
An enolate performs a Michael addition onto an enone, forming a new C–C bond and a 1,5-diketone — the same conjugate addition covered earlier, now setting up ring formation.
Step 2: Intramolecular aldol
Under the same basic conditions, an intramolecular aldol addition then connects the two ends of that diketone chain, closing a new six-membered ring.
Step 3: Dehydration to the enone
Dehydration (E1cb, as in the aldol condensation) gives a conjugated cyclohexenone — the two mechanisms you already know, chained together to build rings.
Abbreviations and terms
- EtOH
- Ethanol. Polar protic solvent.
- NaOEt
- Sodium ethoxide. Alkoxide base matched to ethyl esters (avoids transesterification).
- KOH
- Potassium hydroxide. Strong aqueous/alcoholic base.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- E1cB
- Elimination, unimolecular conjugate base. Deprotonation first to a carbanion, then loss of the leaving group.
- ee
- Enantiomeric excess. How much more of one enantiomer than the other is present.
How it compares with related reactions
| Robinson annulation | Baylis-Hillman reaction | Claisen-Schmidt condensation | |
|---|---|---|---|
| Reagents | Ketone + methyl vinyl ketone (MVK); NaOEt or KOH | Activated alkene (methyl acrylate), aldehyde, DABCO (10–100 mol %) | Methyl ketone (ArCOCH₃), ArCHO (no α-H), NaOH or KOH |
| Conditions | EtOH, 25–80 °C; heat for dehydration | Neat or MeOH/CH₃CN, 25 °C, days (slow) | EtOH/H₂O, 0–25 °C |
| Stereochemistry | Quaternary stereocentre; often racemic (proline gives ee) | Racemic unless chiral amine/Brønsted acid used | E-chalcone (thermodynamic) |
| Rate / selectivity | Michael first, then intramolecular aldol; E1cB dehydration last | Proton transfer/elimination is rate-limiting; accelerated by protic additives | Aldol addition reversible; E1cB dehydration drives it forward |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Robinson annulation?
Ketone + methyl vinyl ketone (MVK); NaOEt or KOH. Conditions: EtOH, 25–80 °C; heat for dehydration.
Which bonds are formed and which are broken?
Formed: C–C (Michael), C–C (aldol), C=C. Broken: α C–H (×2), C=C of MVK, C–OH.
What is the stereochemical outcome?
Quaternary stereocentre; often racemic (proline gives ee)
What controls the rate or the selectivity?
Michael first, then intramolecular aldol; E1cB dehydration last
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go