Activated-DMSO oxidation
Corey-Kim oxidation
How the Corey-Kim oxidation 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: NCS, Me₂S, then alcohol, then Et₃N. Conditions: CH₂Cl₂ or toluene, −25 → 0 °C (higher than Swern). Bonds formed: C=O (carbonyl), Me₂S; bonds broken: O–H, α C–H, N–Cl. Stereochemistry: No stereocentre at carbonyl; α-epimerisation possible with Et₃N. Rate and selectivity: Alkoxysulfonium formation fast; ylide elimination via 5-membered TS.
At a glance
Step 1: NCS activates Me₂S
N-chlorosuccinimide activates dimethyl sulfide's sulfur, forming a chlorosulfonium species — a close cousin of the chlorosulfonium intermediate used to activate DMSO in the Swern oxidation, just built from a different sulfide.
Step 2: Alkoxysulfonium, then ylide
The alcohol's oxygen displaces chloride, forming an alkoxysulfonium salt; base then removes a proton from the sulfur's methyl group in the same intramolecular, five-membered E1cb-like elimination used throughout this family of oxidations.
Step 3: Five-membered elimination
This ejects dimethyl sulfide and delivers the aldehyde — mechanistically almost identical to Swern, this variant is often preferred when oxalyl chloride's low-temperature requirements are inconvenient, since NCS activation can run at higher temperature.
Abbreviations and terms
- DMSO
- Dimethyl sulfoxide. Polar aprotic solvent; also the oxidant in Swern/Kornblum-type reactions.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- Et3N
- Triethylamine. Common tertiary-amine base that scavenges HCl.
- NCS
- N-Chlorosuccinimide. Electrophilic chlorine source.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- E1cB
- Elimination, unimolecular conjugate base. Deprotonation first to a carbanion, then loss of the leaving group.
How it compares with related reactions
| Corey-Kim oxidation | Moffatt oxidation | Swern oxidation of a primary alcohol | |
|---|---|---|---|
| Reagents | NCS, Me₂S, then alcohol, then Et₃N | DMSO, DCC, cat. H₃PO₄ (or pyridinium TFA) | DMSO, (COCl)₂, then Et₃N |
| Conditions | CH₂Cl₂ or toluene, −25 → 0 °C (higher than Swern) | DMSO/benzene, 25 °C | CH₂Cl₂, –78 °C then warm to 25 °C |
| Stereochemistry | No stereocentre at carbonyl; α-epimerisation possible with Et₃N | No stereocentre at carbonyl; α-epimerisation possible | Retains α-stereocentres (no epimerization) |
| Rate / selectivity | Alkoxysulfonium formation fast; ylide elimination via 5-membered TS | Acid-catalysed DCC activation; ylide elimination fast | Activation at –78 °C; ylide collapse fast on warming |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Corey-Kim oxidation?
NCS, Me₂S, then alcohol, then Et₃N. Conditions: CH₂Cl₂ or toluene, −25 → 0 °C (higher than Swern).
Which bonds are formed and which are broken?
Formed: C=O (carbonyl), Me₂S. Broken: O–H, α C–H, N–Cl.
What is the stereochemical outcome?
No stereocentre at carbonyl; α-epimerisation possible with Et₃N
What controls the rate or the selectivity?
Alkoxysulfonium formation fast; ylide elimination via 5-membered TS
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