Alkene synthesis — sulfone-based
Julia-Kocienski olefination
How the Julia-Kocienski olefination 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: 1-phenyl-1H-tetrazol-5-yl (PT) sulfone, KHMDS (or NaHMDS, LiHMDS), aldehyde. Conditions: THF or DME, –78 °C → 25 °C. Bonds formed: C=C; SO₂; PT–O⁻; bonds broken: C=O π; C–S; S–C(het). Stereochemistry: Highly E-selective (anti-adduct, then anti elimination). Rate and selectivity: One-pot; Smiles shift and elimination are fast after addition.
At a glance
Step 1: Sulfonyl carbanion adds to the aldehyde
A metalated heteroarylsulfone's carbanion (stabilized by the adjacent sulfone and heterocycle) attacks an aldehyde's carbonyl carbon, forming an alkoxide.
Step 2: Smiles rearrangement: PT moves S → O
That alkoxide attacks the adjacent heterocycle's ipso carbon intramolecularly (a Smiles rearrangement), migrating the heteroaryl ring from sulfur to oxygen and leaving the sulfonyl group on carbon as a good leaving group.
Step 3: Fragmentation to alkene
Fragmentation ejects SO₂ and the heteroaryl-oxide anion, forming the new C=C bond directly — a robust, highly E-selective alternative to the Wittig for hindered substrates.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- LiHMDS
- Lithium hexamethyldisilazide. Strong, bulky, non-nucleophilic base (pKa ≈ 26).
- NaHMDS
- Sodium hexamethyldisilazide. Strong, bulky, non-nucleophilic base.
- KHMDS
- Potassium hexamethyldisilazide. Strong, bulky base that favours more reactive (“naked”) enolates.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- Meisenheimer
- Meisenheimer complex. The anionic cyclohexadienyl intermediate of SNAr stabilised by electron-withdrawing groups.
How it compares with related reactions
| Julia-Kocienski olefination | Peterson olefination | Horner-Wadsworth-Emmons (HWE) reaction | |
|---|---|---|---|
| Reagents | 1-phenyl-1H-tetrazol-5-yl (PT) sulfone, KHMDS (or NaHMDS, LiHMDS), aldehyde | Me₃SiCH₂⁻ (from Me₃SiCH₂Cl, Mg or n-BuLi), ketone/aldehyde | Phosphonate ester (EtO)₂P(O)CH₂CO₂Et, NaH or NaOMe, aldehyde |
| Conditions | THF or DME, –78 °C → 25 °C | THF, –78 → 25 °C; base (KH) or acid (H₂SO₄, BF₃) for elimination | THF or DME, 0–25 °C |
| Stereochemistry | Highly E-selective (anti-adduct, then anti elimination) | Basic: syn elimination; acid: anti elimination (opposite alkene geometry) | Strong E-selectivity (trans) |
| Rate / selectivity | One-pot; Smiles shift and elimination are fast after addition | Alkoxide addition fast; elimination driven by Si–O bond (≈ 110 kcal/mol) | Aldehyde addition rate-limiting; water-soluble phosphate easily removed |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Julia-Kocienski olefination?
1-phenyl-1H-tetrazol-5-yl (PT) sulfone, KHMDS (or NaHMDS, LiHMDS), aldehyde. Conditions: THF or DME, –78 °C → 25 °C.
Which bonds are formed and which are broken?
Formed: C=C; SO₂; PT–O⁻. Broken: C=O π; C–S; S–C(het).
What is the stereochemical outcome?
Highly E-selective (anti-adduct, then anti elimination)
What controls the rate or the selectivity?
One-pot; Smiles shift and elimination are fast after addition
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