Ti-mediated reductive coupling
McMurry coupling
How the McMurry coupling 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: TiCl₃ or TiCl₄, Zn (or Zn–Cu, LiAlH₄). Conditions: THF, reflux, inert atmosphere. Bonds formed: C=C (alkene); bonds broken: 2 × C=O. Stereochemistry: Mixture of E/Z for unsymmetrical alkenes. Rate and selectivity: Pinacol coupling at low T; deoxygenation needs heat.
At a glance
Step 1: Ti(0) gives electrons: ketyl radicals
Low-valent titanium (generated in situ from TiCl₃ or TiCl₄ and a reducing metal like Zn) transfers electrons to two separate carbonyl compounds, generating two ketyl radical anions bound to the titanium surface.
Step 2: Radical coupling: Ti-pinacolate
These two radicals couple directly on the metal surface — the same radical-radical combination logic as radical polymerization termination — forming a new C–C bond and a titanium-bound 1,2-diolate, essentially a surface-mediated pinacol coupling.
Step 3: Deoxygenation: alkene
The titanium diolate then undergoes a syn-elimination (mechanistically related to the Corey-Winter olefination), losing both oxygens as titanium oxide species and forming the new alkene directly — this reductive dimerization is one of the only general ways to join two separate carbonyl compounds into a single symmetric or unsymmetric alkene.
Abbreviations and terms
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- LiAlH4
- Lithium aluminium hydride. Powerful hydride (H⁻) donor; reduces esters, acids, amides to alcohols/amines.
- TiCl4
- Titanium tetrachloride. Strong, oxophilic Lewis acid that chelates carbonyls.
How it compares with related reactions
| McMurry coupling | Borch reductive amination | Corey-House synthesis | |
|---|---|---|---|
| Reagents | TiCl₃ or TiCl₄, Zn (or Zn–Cu, LiAlH₄) | Amine, ketone/aldehyde, NaBH₃CN | 2 R–Li, CuI; then R′–X (primary alkyl iodide, bromide or tosylate) |
| Conditions | THF, reflux, inert atmosphere | MeOH, pH 6–7 (AcOH), 25 °C | Et₂O or THF, –78 to 25 °C |
| Stereochemistry | Mixture of E/Z for unsymmetrical alkenes | New stereocentre usually racemic (unless chiral amine/ketone) | Inversion at a stereogenic sp³ C–X in many cases; best with 1° halides |
| Rate / selectivity | Pinacol coupling at low T; deoxygenation needs heat | Iminium formation is rate-limiting; iminium reduced much faster than ketone at this pH | Soft, low-polarity C–Cu bond: little elimination or carbonyl attack vs RLi |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the McMurry coupling?
TiCl₃ or TiCl₄, Zn (or Zn–Cu, LiAlH₄). Conditions: THF, reflux, inert atmosphere.
Which bonds are formed and which are broken?
Formed: C=C (alkene). Broken: 2 × C=O.
What is the stereochemical outcome?
Mixture of E/Z for unsymmetrical alkenes
What controls the rate or the selectivity?
Pinacol coupling at low T; deoxygenation needs heat
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go