Cu-catalyzed aerobic coupling
Chan-Lam coupling
How the Chan-Lam 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: ArB(OH)₂, R₂NH or ROH, Cu(OAc)₂ (cat. to stoich.), base (Et₃N or pyridine), O₂. Conditions: CH₂Cl₂ or MeOH, 25 °C, open to air. Bonds formed: Ar–N (or Ar–O) C–heteroatom bond; bonds broken: C–B; N–H (O–H). Stereochemistry: No stereocenters formed. Rate and selectivity: Transmetalation and N-coordination fast; reoxidation by O₂ can limit turnover.
At a glance
Step 1: Transmetalation from boron to Cu(II)
Unlike every Pd-catalyzed coupling so far, this reaction never goes through oxidative addition: a boronic acid transmetalates directly onto a Cu(II) center, transferring its organic group without ever needing an aryl halide.
Step 2: Amine binds; C–N reductive elimination
An amine (or alcohol) coordinates to the same copper center as a second ligand, and reductive elimination forges the new C–N (or C–O) bond directly, reducing Cu(II) to Cu(0)/Cu(I).
Step 3: Aerobic reoxidation closes the cycle
Ambient O₂ reoxidizes the reduced copper back to Cu(II), closing the catalytic cycle — this aerobic reoxidation is what lets Chan-Lam coupling run efficiently at room temperature with air as the only stoichiometric oxidant needed.
Abbreviations and terms
- Ar
- Aryl group. Any aromatic ring substituent such as phenyl.
- Me
- Methyl. –CH₃.
- Ph
- Phenyl. –C₆H₅.
- OAc
- Acetoxy. –OC(=O)CH₃, an acetate group.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- MeOH
- Methanol. Polar protic solvent (also a nucleophile in solvolysis).
- AcOH
- Acetic acid. Weak acid and polar protic solvent.
- Et3N
- Triethylamine. Common tertiary-amine base that scavenges HCl.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
How it compares with related reactions
| Chan-Lam coupling | Buchwald-Hartwig amination | Buchwald-Hartwig etherification | |
|---|---|---|---|
| Reagents | ArB(OH)₂, R₂NH or ROH, Cu(OAc)₂ (cat. to stoich.), base (Et₃N or pyridine), O₂ | ArBr, R₂NH, Pd₂(dba)₃ / bulky phosphine (XPhos, BINAP), NaOtBu | ArBr, ROH, Pd₂(dba)₃ or Pd(OAc)₂ / bulky biaryl phosphine (RockPhos, tBuBrettPhos), Cs₂CO₃ or NaOtBu |
| Conditions | CH₂Cl₂ or MeOH, 25 °C, open to air | Toluene or dioxane, 80–110 °C | Toluene or dioxane, 80–100 °C |
| Stereochemistry | No stereocenters formed | No new stereocentre; retention of aryl geometry | No new stereocentre; aryl geometry retained |
| Rate / selectivity | Transmetalation and N-coordination fast; reoxidation by O₂ can limit turnover | Bulky, electron-rich ligand speeds oxidative addition and C–N reductive elimination | C–O reductive elimination is slow, so very bulky ligands are needed |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Chan-Lam coupling?
ArB(OH)₂, R₂NH or ROH, Cu(OAc)₂ (cat. to stoich.), base (Et₃N or pyridine), O₂. Conditions: CH₂Cl₂ or MeOH, 25 °C, open to air.
Which bonds are formed and which are broken?
Formed: Ar–N (or Ar–O) C–heteroatom bond. Broken: C–B; N–H (O–H).
What is the stereochemical outcome?
No stereocenters formed
What controls the rate or the selectivity?
Transmetalation and N-coordination fast; reoxidation by O₂ can limit turnover
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam