Zinc-mediated carbonyl addition
Reformatsky reaction
How the Reformatsky reaction 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: α-Bromo ester, Zn (activated), aldehyde or ketone; then H₃O⁺. Conditions: THF or benzene/Et₂O, 40–80 °C. Bonds formed: C–Zn; C–C; O–Zn → C–OH; bonds broken: C–Br; C=O π. Stereochemistry: Chair TS; modest syn/anti selectivity. Rate and selectivity: Zn insertion (needs activation) is the slow step.
At a glance
Step 1: Zn inserts into C–Br
Zinc metal inserts into the carbon-halogen bond of an α-halo ester, generating an organozinc reagent — milder and more functional-group-tolerant than a lithium or magnesium enolate equivalent.
Step 2: Zinc enolate adds to the carbonyl
This zinc enolate adds to an aldehyde or ketone's carbonyl carbon through a chelated transition state, exactly paralleling the Grignard mechanism but with zinc's reduced basicity avoiding competing enolization of the substrate itself.
Step 3: Aqueous workup
Aqueous workup gives a β-hydroxy ester — this reaction lets chemists perform an effective 'ester enolate aldol addition' on substrates too base-sensitive to survive a conventional strong-base-generated enolate.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- Et2O
- Diethyl ether. Low-boiling ether solvent, classic for Grignard reagents.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
How it compares with related reactions
| Reformatsky reaction | Acid-catalyzed hydration of an alkene | Br₂ addition to an alkene (vicinal dihalide) | |
|---|---|---|---|
| Reagents | α-Bromo ester, Zn (activated), aldehyde or ketone; then H₃O⁺ | Dilute H₂SO₄ or H₃PO₄ (H₃O⁺), H₂O | Br₂ |
| Conditions | THF or benzene/Et₂O, 40–80 °C | 25–100 °C; heat and excess water favour the alcohol | CH₂Cl₂ or CCl₄, 25 °C, dark |
| Stereochemistry | Chair TS; modest syn/anti selectivity | Planar carbocation: racemic; Markovnikov regiochemistry | Anti addition via bromonium; trans product (racemic) |
| Rate / selectivity | Zn insertion (needs activation) is the slow step | Protonation of the alkene is rate-determining | Bromonium formation rate-limiting; fast |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Reformatsky reaction?
α-Bromo ester, Zn (activated), aldehyde or ketone; then H₃O⁺. Conditions: THF or benzene/Et₂O, 40–80 °C.
Which bonds are formed and which are broken?
Formed: C–Zn; C–C; O–Zn → C–OH. Broken: C–Br; C=O π.
What is the stereochemical outcome?
Chair TS; modest syn/anti selectivity
What controls the rate or the selectivity?
Zn insertion (needs activation) is the slow step
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