Furan oxidative ring expansion
Achmatowicz rearrangement
How the Achmatowicz rearrangement 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: NBS, THF/H₂O, NaHCO₃ (or mCPBA; or VO(acac)₂/t-BuOOH; or Oxone/KBr). Conditions: 0 °C, then 25 °C. Bonds formed: C–O (hemiacetal ring); C=O; C=C (enone); bonds broken: furan aromaticity; C–O (furan ring). Stereochemistry: New anomeric center (α/β mix); substituent at C2 retained. Rate and selectivity: Oxidative furan opening is fast; hemiketalization is rapid and reversible.
At a glance
Step 1: Oxidative opening of the furan
An oxidant (NBS or mCPBA) adds across furfuryl alcohol's ring, opening the furan and generating a reactive, conjugated dicarbonyl-type intermediate — related to the ring-opening step at the start of the Piancatelli rearrangement.
Step 2: Pendant OH closes a hemiacetal
The pendant primary alcohol attacks intramolecularly, closing a new six-membered ring in a fresh hemiketal-forming cyclization.
Step 3: Overall: furan to dihydropyranone
The product is a dihydropyranone bearing a new stereocenter and an enone — this reliably converts cheap, biomass-derived furfuryl alcohols into densely functionalized six-membered oxygen heterocycles used throughout carbohydrate and natural product synthesis.
Abbreviations and terms
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- mCPBA
- meta-Chloroperoxybenzoic acid. Peracid that transfers an electrophilic oxygen (epoxidation, Baeyer–Villiger).
- NBS
- N-Bromosuccinimide. Source of a low, steady concentration of Br₂/Br• for allylic/benzylic bromination.
- Oxone
- Potassium peroxymonosulfate. Inexpensive solid peracid-type oxidant.
- HBr
- Hydrobromic acid. Strong acid; bromide is a good nucleophile.
- acac
- Acetylacetonate. Bidentate O,O-chelating ligand.
How it compares with related reactions
| Achmatowicz rearrangement | Biginelli reaction | Bischler indole synthesis | |
|---|---|---|---|
| Reagents | NBS, THF/H₂O, NaHCO₃ (or mCPBA; or VO(acac)₂/t-BuOOH; or Oxone/KBr) | Aldehyde, urea, ethyl acetoacetate, HCl or Lewis acid | Aniline (excess), α-haloketone (PhCOCH₂Br) |
| Conditions | 0 °C, then 25 °C | EtOH, reflux (or neat, 90 °C) | Step 1: 25–80 °C; step 2: acid (or aniline·HBr), 150–200 °C |
| Stereochemistry | New anomeric center (α/β mix); substituent at C2 retained | C4 stereocentre formed (racemic unless chiral acid catalyst) | None |
| Rate / selectivity | Oxidative furan opening is fast; hemiketalization is rapid and reversible | Iminium formation or its Mannich-type capture is rate-limiting | Cyclisation (high T) is slow; SN2 alkylation is fast |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Achmatowicz rearrangement?
NBS, THF/H₂O, NaHCO₃ (or mCPBA; or VO(acac)₂/t-BuOOH; or Oxone/KBr). Conditions: 0 °C, then 25 °C.
Which bonds are formed and which are broken?
Formed: C–O (hemiacetal ring); C=O; C=C (enone). Broken: furan aromaticity; C–O (furan ring).
What is the stereochemical outcome?
New anomeric center (α/β mix); substituent at C2 retained
What controls the rate or the selectivity?
Oxidative furan opening is fast; hemiketalization is rapid and reversible
Study guides that help with this reaction
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go
- How to answer mechanism questions in an exam