Carbodiimide-activated DMSO oxidation
Moffatt oxidation
How the Moffatt 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: DMSO, DCC, cat. H₃PO₄ (or pyridinium TFA). Conditions: DMSO/benzene, 25 °C. Bonds formed: C=O (carbonyl), Me₂S, dicyclohexylurea; bonds broken: O–H, α C–H, DCC C=N. Stereochemistry: No stereocentre at carbonyl; α-epimerisation possible. Rate and selectivity: Acid-catalysed DCC activation; ylide elimination fast.
At a glance
Step 1: DCC activates DMSO
DCC (the same carbodiimide used in peptide coupling) activates DMSO's oxygen, forming an activated sulfoxonium species with a good leaving group — a different activation strategy from Swern's oxalyl chloride, but the same underlying goal.
Step 2: Alcohol displaces the urea
The alcohol's oxygen displaces the activated leaving group, forming an alkoxysulfonium salt exactly as in Swern and Corey-Kim oxidations.
Step 3: Ylide elimination to the ketone
Intramolecular proton removal (E1cb-like, as throughout this family) ejects dimethyl sulfide and forms the carbonyl, while DCC is converted to dicyclohexylurea — historically the first of these activated-DMSO oxidations, later superseded in popularity by the milder, more reliable Swern procedure.
Abbreviations and terms
- DMSO
- Dimethyl sulfoxide. Polar aprotic solvent; also the oxidant in Swern/Kornblum-type reactions.
- TFA
- Trifluoroacetic acid. A strong organic acid (pKa ≈ 0.5), used to remove Boc groups and protonate carbonyls.
- DCC
- N,N′-Dicyclohexylcarbodiimide. Dehydrating coupling agent: activates RCO₂H as an O-acylisourea; byproduct DCU precipitates.
- DCU
- Dicyclohexylurea. Insoluble by-product of DCC couplings.
- E1cB
- Elimination, unimolecular conjugate base. Deprotonation first to a carbanion, then loss of the leaving group.
How it compares with related reactions
| Moffatt oxidation | Corey-Kim oxidation | Swern oxidation of a primary alcohol | |
|---|---|---|---|
| Reagents | DMSO, DCC, cat. H₃PO₄ (or pyridinium TFA) | NCS, Me₂S, then alcohol, then Et₃N | DMSO, (COCl)₂, then Et₃N |
| Conditions | DMSO/benzene, 25 °C | CH₂Cl₂ or toluene, −25 → 0 °C (higher than Swern) | CH₂Cl₂, –78 °C then warm to 25 °C |
| Stereochemistry | No stereocentre at carbonyl; α-epimerisation possible | No stereocentre at carbonyl; α-epimerisation possible with Et₃N | Retains α-stereocentres (no epimerization) |
| Rate / selectivity | Acid-catalysed DCC activation; ylide elimination fast | Alkoxysulfonium formation fast; ylide elimination via 5-membered TS | 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 Moffatt oxidation?
DMSO, DCC, cat. H₃PO₄ (or pyridinium TFA). Conditions: DMSO/benzene, 25 °C.
Which bonds are formed and which are broken?
Formed: C=O (carbonyl), Me₂S, dicyclohexylurea. Broken: O–H, α C–H, DCC C=N.
What is the stereochemical outcome?
No stereocentre at carbonyl; α-epimerisation possible
What controls the rate or the selectivity?
Acid-catalysed DCC activation; ylide elimination fast
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