Conjugate (1,4) addition
Michael addition: malonate enolate + methyl vinyl ketone
How the Michael addition 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: Diethyl malonate, cat. NaOEt; methyl vinyl ketone (MVK). Conditions: EtOH, 0–25 °C. Bonds formed: C–C σ (to the β-carbon); bonds broken: C=C π (of the enone); α C–H. Stereochemistry: Prochiral enolate; new stereocentre formed racemic unless catalyst is chiral. Rate and selectivity: Soft, stabilised nucleophiles favour 1,4-(conjugate) over 1,2-addition.
At a glance
Step 1: Deprotonate the active methylene
Base deprotonates diethyl malonate's doubly-activated C–H (flanked by two ester groups), forming a stabilized enolate nucleophile.
Step 2: 1,4-Addition to the enone
Rather than attacking the ketone's carbonyl carbon directly, the enolate attacks the β-carbon of the enone. Electrons flow in one continuous path: nucleophile → β-carbon → through the C=C → onto oxygen — a 1,4- rather than 1,2-addition.
Step 3: Protonation gives the Michael adduct
Protonation gives the Michael adduct: a new C–C bond formed at the position that was once the alkene, with the ketone's carbonyl fully restored.
Abbreviations and terms
- EtOH
- Ethanol. Polar protic solvent.
- NaOEt
- Sodium ethoxide. Alkoxide base matched to ethyl esters (avoids transesterification).
- pKa
- Acid-dissociation constant (–log). Lower pKa = stronger acid; used to judge which proton a base removes.
How it compares with related reactions
| Michael addition | Mukaiyama-Michael reaction | Acid-catalyzed hydration of an alkene | |
|---|---|---|---|
| Reagents | Diethyl malonate, cat. NaOEt; methyl vinyl ketone (MVK) | Silyl enol ether, α,β-unsaturated ketone, TiCl₄ (or other Lewis acid) | Dilute H₂SO₄ or H₃PO₄ (H₃O⁺), H₂O |
| Conditions | EtOH, 0–25 °C | CH₂Cl₂, –78 °C; aqueous workup | 25–100 °C; heat and excess water favour the alcohol |
| Stereochemistry | Prochiral enolate; new stereocentre formed racemic unless catalyst is chiral | Enol-ether geometry and Lewis acid control syn/anti; new stereocentres possible | Planar carbocation: racemic; Markovnikov regiochemistry |
| Rate / selectivity | Soft, stabilised nucleophiles favour 1,4-(conjugate) over 1,2-addition | Lewis acid binding to the enone drives the conjugate addition | Protonation of the alkene is rate-determining |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Michael addition?
Diethyl malonate, cat. NaOEt; methyl vinyl ketone (MVK). Conditions: EtOH, 0–25 °C.
Which bonds are formed and which are broken?
Formed: C–C σ (to the β-carbon). Broken: C=C π (of the enone); α C–H.
What is the stereochemical outcome?
Prochiral enolate; new stereocentre formed racemic unless catalyst is chiral
What controls the rate or the selectivity?
Soft, stabilised nucleophiles favour 1,4-(conjugate) over 1,2-addition
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