Alkyne synthesis from an aldehyde
Corey-Fuchs reaction
How the Corey-Fuchs 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: 1) CBr₄, PPh₃ 2) 2 equiv n-BuLi, then H₂O. Conditions: CH₂Cl₂, 0 °C; then THF, –78 °C. Bonds formed: C=C (dibromoalkene); C≡C; Ph₃P=O; bonds broken: C=O; C–Br; vinylic C–H. Stereochemistry: No stereochemistry (alkyne is linear). Rate and selectivity: Wittig step fast; Li–Br exchange very fast at –78 °C.
At a glance
Step 1: Dibromo-ylide + aldehyde (Wittig)
CBr₄ and PPh₃ combine to generate a phosphorus ylide bearing two bromines; this ylide reacts with an aldehyde in an ordinary Wittig-type olefination, forming a 1,1-dibromoalkene.
Step 2: First n-BuLi: elimination to bromoalkyne, then Li–Br exchange
Two equivalents of strong base (n-BuLi) sequentially deprotonate and eliminate both bromides from the dibromoalkene, in a double elimination that passes through a vinylidene carbene-like transition state.
Step 3: Aqueous quench: terminal alkyne
The result is a terminal alkyne, extended by one carbon relative to the original aldehyde — a reliable two-step way to convert an aldehyde directly into an alkyne without needing to pre-install a leaving group.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- Ph
- Phenyl. –C₆H₅.
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- n-BuLi
- n-Butyllithium. Very strong base/nucleophile (pKa of butane ≈ 50); deprotonates alkynes and does lithium–halogen exchange.
- PPh3
- Triphenylphosphine. Nucleophilic phosphine; forms very strong P=O bonds, driving Wittig, Appel and Mitsunobu reactions.
- TPPO
- Triphenylphosphine oxide. The thermodynamic sink of Wittig/Mitsunobu/Appel reactions.
How it compares with related reactions
| Corey-Fuchs reaction | Seyferth-Gilbert / Ohira-Bestmann homologation | Aza-Wittig reaction | |
|---|---|---|---|
| Reagents | 1) CBr₄, PPh₃ 2) 2 equiv n-BuLi, then H₂O | Seyferth–Gilbert: (MeO)₂P(O)CHN₂, KOtBu; Ohira–Bestmann: (MeO)₂P(O)C(N₂)C(O)CH₃, K₂CO₃, MeOH | R–N=PPh₃ (from R–N₃ + PPh₃, Staudinger), aldehyde or ketone |
| Conditions | CH₂Cl₂, 0 °C; then THF, –78 °C | THF –78 °C (SG); MeOH, 25 °C (OB) | THF or toluene, 25–110 °C, anhydrous |
| Stereochemistry | No stereochemistry (alkyne is linear) | None (alkyne) | Imine E/Z set at ring collapse; no stereocentre needed |
| Rate / selectivity | Wittig step fast; Li–Br exchange very fast at –78 °C | Carbene formation/1,2-H shift fast; addition is rate-limiting | Cycloreversion is fast; driven by strong P=O bond (≈ 130 kcal/mol) |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Corey-Fuchs reaction?
1) CBr₄, PPh₃ 2) 2 equiv n-BuLi, then H₂O. Conditions: CH₂Cl₂, 0 °C; then THF, –78 °C.
Which bonds are formed and which are broken?
Formed: C=C (dibromoalkene); C≡C; Ph₃P=O. Broken: C=O; C–Br; vinylic C–H.
What is the stereochemical outcome?
No stereochemistry (alkyne is linear)
What controls the rate or the selectivity?
Wittig step fast; Li–Br exchange very fast at –78 °C
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