Sulfonium ylide chemistry
Corey-Chaykovsky epoxidation/cyclopropanation
How the Corey-Chaykovsky epoxidation/cyclopropanation 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: Me₃S⁺ I⁻, NaH (or n-BuLi), DMSO/THF. Conditions: 0–25 °C. Bonds formed: C–C; C–O (epoxide) or C–C (cyclopropane); bonds broken: C=O π (or C=C π); C–S. Stereochemistry: Diastereoselectivity set at the betaine stage. Rate and selectivity: Ylide formation fast; ring closure by SN2.
At a glance
Step 1: Base makes the sulfonium ylide
Base deprotonates a trimethylsulfonium salt, forming a sulfonium ylide — nucleophilic carbon stabilized by the adjacent, electropositive sulfur, much like the Wittig ylide's phosphorus.
Step 2: Ylide adds to C=O
The ylide attacks a ketone's carbonyl carbon (or a Michael acceptor's β-carbon), forming a betaine intermediate — but unlike phosphorus, sulfur's leaving-group ability lets the ring close differently.
Step 3: Ring closure: epoxide or cyclopropane
Intramolecular SN2 displacement of the sulfide leaving group closes either an epoxide (from a carbonyl) or a cyclopropane (from a Michael acceptor), depending on the substrate — a rare case where one ylide gives two different ring products.
Abbreviations and terms
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- DMSO
- Dimethyl sulfoxide. Polar aprotic solvent; also the oxidant in Swern/Kornblum-type reactions.
- n-BuLi
- n-Butyllithium. Very strong base/nucleophile (pKa of butane ≈ 50); deprotonates alkynes and does lithium–halogen exchange.
- NaH
- Sodium hydride. Insoluble, irreversible base: removes H⁺ and bubbles off H₂.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- SN2
- Bimolecular nucleophilic substitution. One concerted step with backside attack and inversion; rate = k[RX][Nu].
How it compares with related reactions
| Corey-Chaykovsky epoxidation/cyclopropanation | Wittig reaction | Aldol condensation | |
|---|---|---|---|
| Reagents | Me₃S⁺ I⁻, NaH (or n-BuLi), DMSO/THF | Ph₃P=CH₂ (ylide, from Ph₃P⁺CH₃ Br⁻ + n-BuLi); acetaldehyde | NaOH or KOH (cat.) |
| Conditions | 0–25 °C | THF, 0 °C → 25 °C; anhydrous, inert atmosphere | H₂O/EtOH, heat 50–100 °C |
| Stereochemistry | Diastereoselectivity set at the betaine stage | Unstabilised ylides: Z-alkene; stabilised: E-alkene | Mostly E-enal (thermodynamic) |
| Rate / selectivity | Ylide formation fast; ring closure by SN2 | Driven by the strong P=O bond of Ph₃P=O | E1cB; loss of HO⁻ from the enolate is rate-determining |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Corey-Chaykovsky epoxidation/cyclopropanation?
Me₃S⁺ I⁻, NaH (or n-BuLi), DMSO/THF. Conditions: 0–25 °C.
Which bonds are formed and which are broken?
Formed: C–C; C–O (epoxide) or C–C (cyclopropane). Broken: C=O π (or C=C π); C–S.
What is the stereochemical outcome?
Diastereoselectivity set at the betaine stage
What controls the rate or the selectivity?
Ylide formation fast; ring closure by SN2
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