Pericyclic — electrocyclization
Nazarov cyclization
How the Nazarov cyclization 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: Divinyl ketone; Brønsted or Lewis acid (H₂SO₄, FeCl₃, BF₃). Conditions: CH₂Cl₂ or neat acid, 0–25 °C. Bonds formed: C–C σ (ring closure); C=C (shifted); bonds broken: C=C π; O–H⁺ (proton lost). Stereochemistry: Conrotatory 4π closure sets ring stereocentres. Rate and selectivity: Often rate-limited by ring closure; EWG/silicon directing groups help.
At a glance
Step 1: Protonation gives pentadienyl cation
Acid protonates a divinyl ketone's carbonyl, generating a conjugated pentadienyl cation spanning all five carbons.
Step 2: Conrotatory 4π electrocyclisation
This cation undergoes a conrotatory 4π electrocyclic ring closure — both ends of the pi system rotate in the same direction as the new σ bond forms, closing a five-membered ring.
Step 3: Loss of proton → cyclopentenone
Loss of a proton from the resulting cyclopentenyl cation gives a cyclopentenone — a reliable way to build five-membered rings using only orbital symmetry, no external nucleophile needed.
Abbreviations and terms
- EWG
- Electron-withdrawing group. A substituent (C=O, NO₂, CN…) that pulls electron density away, stabilising anions and activating electrophiles.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- Lewis acid
- Lewis acid. Electron-pair acceptor (AlCl₃, BF₃, TiCl₄…) that activates carbonyls and halides.
- BF3
- Boron trifluoride. Lewis acid (usually as the Et₂O complex).
- H2SO4
- Sulfuric acid. Strong acid and dehydrating agent.
How it compares with related reactions
| Nazarov cyclization | 1,3-dipolar cycloaddition | 2-Aza-Cope rearrangement | |
|---|---|---|---|
| Reagents | Divinyl ketone; Brønsted or Lewis acid (H₂SO₄, FeCl₃, BF₃) | Nitrile oxide (from hydroximoyl chloride + Et₃N, or ArCH=NOH + NCS/base), alkene | Homoallylic amine, aldehyde (to give the iminium), acid |
| Conditions | CH₂Cl₂ or neat acid, 0–25 °C | CH₂Cl₂ or toluene, 25–80 °C; no catalyst | Mild heat or RT (cationic variant), CH₂Cl₂ or MeCN |
| Stereochemistry | Conrotatory 4π closure sets ring stereocentres | Suprafacial, stereospecific (alkene geometry retained); 5-substituted regioisomer favored | Chair TS; stereo transferred |
| Rate / selectivity | Often rate-limited by ring closure; EWG/silicon directing groups help | Concerted, thermal; HOMO/LUMO of dipole and alkene both matter | Faster than all-carbon Cope (cationic N) |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Nazarov cyclization?
Divinyl ketone; Brønsted or Lewis acid (H₂SO₄, FeCl₃, BF₃). Conditions: CH₂Cl₂ or neat acid, 0–25 °C.
Which bonds are formed and which are broken?
Formed: C–C σ (ring closure); C=C (shifted). Broken: C=C π; O–H⁺ (proton lost).
What is the stereochemical outcome?
Conrotatory 4π closure sets ring stereocentres
What controls the rate or the selectivity?
Often rate-limited by ring closure; EWG/silicon directing groups help
Study guides that help with this reaction
- Pericyclic reactions explained: cycloadditions, electrocyclisations and sigmatropic shifts
- Stereochemistry in mechanisms: inversion, retention, syn and anti