Inorganic — cobalt-stabilized cation
Nicholas reaction
How the Nicholas 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) Co₂(CO)₈ 2) BF₃·OEt₂ (or HBF₄), Nu–H 3) CAN (or NMO, I₂). Conditions: CH₂Cl₂, −78 → 25 °C; decomplexation at 0 °C. Bonds formed: C–Nu bond at propargylic carbon; bonds broken: C–OH; Co–alkyne (final step). Stereochemistry: Cation is planar; Nu adds from the less hindered face. Rate and selectivity: Ionisation is fast: Co₂(CO)₆ delocalises the cation (metal-stabilised).
At a glance
Step 1: Ionisation to the Co-stabilised cation
Co₂(CO)₆ coordinates a propargylic alcohol's alkyne, and under mild Lewis or Brønsted acid, the propargylic C–O bond ionizes — the cobalt cluster dramatically stabilizes the resulting propargyl cation, which would otherwise be far too unstable to isolate or use deliberately.
Step 2: Nucleophile attacks the cation
This cobalt-stabilized cation is now a bench-stable, isolable electrophile that reacts with a wide range of nucleophiles (alcohols, silyl enol ethers, arenes) at the propargylic carbon, exactly like any stabilized carbocation would.
Step 3: Oxidative decomplexation
Oxidative removal of the cobalt (with cerium(IV) or similar) unmasks the alkyne once the new C–nucleophile bond is in place — the cobalt cluster's whole job was temporary: protecting the alkyne while simultaneously turning an otherwise-inaccessible cation into a usable synthetic handle.
Abbreviations and terms
- Nu
- Nucleophile. An electron-rich species that donates an electron pair to form a new bond.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- CAN
- Ceric ammonium nitrate. One-electron Ce(IV) oxidant.
- NMO
- N-Methylmorpholine N-oxide. Co-oxidant that reoxidises Os(VI) to Os(VIII).
- BF3
- Boron trifluoride. Lewis acid (usually as the Et₂O complex).
- CO
- Carbon monoxide (carbonyl ligand). σ-donor / strong π-acceptor ligand; also a C1 building block.
How it compares with related reactions
| Nicholas reaction | Associative ligand substitution at a square-planar Pt(II) complex | Asymmetric phase-transfer catalysis | |
|---|---|---|---|
| Reagents | 1) Co₂(CO)₈ 2) BF₃·OEt₂ (or HBF₄), Nu–H 3) CAN (or NMO, I₂) | K₂[PtCl₄] + NH₃ (aq) | Chiral cinchona-derived Q*⁺Br⁻ (1–10 mol%), 50% aq. KOH, glycine imine tBu ester, BnBr |
| Conditions | CH₂Cl₂, −78 → 25 °C; decomplexation at 0 °C | H₂O, 25 °C | Toluene/CH₂Cl₂, 0 °C, vigorous stirring |
| Stereochemistry | Cation is planar; Nu adds from the less hindered face | Trigonal-bipyramidal intermediate; retention of geometry | High ee: chiral ion pair shields one enolate face |
| Rate / selectivity | Ionisation is fast: Co₂(CO)₆ delocalises the cation (metal-stabilised) | Rate = k₁[Pt] + k₂[Pt][NH₃] (associative; entering-ligand dependent) | Alkylation of the ion pair is rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Nicholas reaction?
1) Co₂(CO)₈ 2) BF₃·OEt₂ (or HBF₄), Nu–H 3) CAN (or NMO, I₂). Conditions: CH₂Cl₂, −78 → 25 °C; decomplexation at 0 °C.
Which bonds are formed and which are broken?
Formed: C–Nu bond at propargylic carbon. Broken: C–OH; Co–alkyne (final step).
What is the stereochemical outcome?
Cation is planar; Nu adds from the less hindered face
What controls the rate or the selectivity?
Ionisation is fast: Co₂(CO)₆ delocalises the cation (metal-stabilised)
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam