Fragmentation
Grob fragmentation
How the Grob fragmentation 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: Substrate with γ-leaving group and donor (e.g. NR₂, O⁻); often base or heat. Conditions: Polar solvent, mild heat. Bonds formed: C=C (or C=N⁺/C=O); free LG; bonds broken: C–C (central σ bond); C–LG. Stereochemistry: Antiperiplanar alignment of donor lone pair, C–C and C–LG. Rate and selectivity: Concerted; favoured by good LG (OTs) and strong donor.
At a glance
Step 1: Donor and leaving group, 1,3-related
A leaving group and an electron-donating group (like an amine or alkoxide) sit 1,3 to each other, anti-periplanar across the connecting bonds.
Step 2: One concerted push of electrons
Electrons flow in a continuous chain: the donor's lone pair pushes into the C–C bond between them, which breaks as the leaving group departs — a single concerted fragmentation, not a stepwise process.
Step 3: Two fragments
The molecule splits into two pieces: a new alkene (or iminium/oxocarbenium ion) forms at the donor end, while the leaving group departs from the other — useful for cleaving rings that are otherwise hard to open.
Abbreviations and terms
- LG
- Leaving group. The group that departs with the bonding electrons (good ones are weak bases: I⁻, Br⁻, TsO⁻…).
- OTs
- Tosylate. p-Toluenesulfonate ester – an excellent leaving group.
How it compares with related reactions
| Grob fragmentation | Eschenmoser-Tanabe fragmentation | 1,3-dipolar cycloaddition | |
|---|---|---|---|
| Reagents | Substrate with γ-leaving group and donor (e.g. NR₂, O⁻); often base or heat | TsNHNH₂, AcOH (or Et₃N); α,β-epoxy ketone | Nitrile oxide (from hydroximoyl chloride + Et₃N, or ArCH=NOH + NCS/base), alkene |
| Conditions | Polar solvent, mild heat | CH₂Cl₂ or AcOH, 0–25 °C | CH₂Cl₂ or toluene, 25–80 °C; no catalyst |
| Stereochemistry | Antiperiplanar alignment of donor lone pair, C–C and C–LG | Alkyne carbons lose stereochemistry | Suprafacial, stereospecific (alkene geometry retained); 5-substituted regioisomer favored |
| Rate / selectivity | Concerted; favoured by good LG (OTs) and strong donor | Hydrazone formation, then fast irreversible fragmentation | Concerted, thermal; HOMO/LUMO of dipole and alkene both matter |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Grob fragmentation?
Substrate with γ-leaving group and donor (e.g. NR₂, O⁻); often base or heat. Conditions: Polar solvent, mild heat.
Which bonds are formed and which are broken?
Formed: C=C (or C=N⁺/C=O); free LG. Broken: C–C (central σ bond); C–LG.
What is the stereochemical outcome?
Antiperiplanar alignment of donor lone pair, C–C and C–LG
What controls the rate or the selectivity?
Concerted; favoured by good LG (OTs) and strong donor
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti