Organocatalysis — dioxirane oxidant
Shi epoxidation
How the Shi epoxidation 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: Chiral fructose-derived ketone (cat.), Oxone (KHSO₅), K₂CO₃ buffer. Conditions: MeCN/H₂O, pH ≈ 10.5, 0 °C. Bonds formed: C–O ×2 (epoxide); dioxirane O–O; bonds broken: C=C π; peroxide O–O. Stereochemistry: Spiro TS: high ee for trans- and trisubstituted alkenes. Rate and selectivity: Oxygen transfer from the dioxirane is rate-limiting.
At a glance
Step 1: Ketone + Oxone → dioxirane
A chiral ketone catalyst reacts with a peroxymonosulfate oxidant (Oxone) to form a reactive dioxirane in situ — a three-membered ring bearing two oxygens, generated fresh from the ketone rather than pre-made and stored.
Step 2: Concerted spiro oxygen transfer
This chiral dioxirane transfers one of its oxygens directly to an alkene, in a concerted, spiro-like transition state where the alkene approaches from whichever face the chiral ketone's own substituents leave open.
Step 3: Epoxide released, ketone regenerated
The epoxide is released and the original ketone catalyst is regenerated, ready to react with more Oxone — because the catalyst is a simple, readily-modified ketone rather than a metal complex, this offers a metal-free complement to the Sharpless and Jacobsen-Katsuki epoxidations.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- Ph
- Phenyl. –C₆H₅.
- MeCN
- Acetonitrile. Polar aprotic solvent.
- K2CO3
- Potassium carbonate. Mild inorganic base.
- Oxone
- Potassium peroxymonosulfate. Inexpensive solid peracid-type oxidant.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- ee
- Enantiomeric excess. How much more of one enantiomer than the other is present.
How it compares with related reactions
| Shi epoxidation | CBS reduction (Corey-Bakshi-Shibata) | MacMillan iminium organocatalysis | |
|---|---|---|---|
| Reagents | Chiral fructose-derived ketone (cat.), Oxone (KHSO₅), K₂CO₃ buffer | (S)- or (R)-Me-CBS oxazaborolidine (5–10 mol%), BH₃·THF or BH₃·SMe₂ | Chiral imidazolidinone·HCl (5–20 mol%), enal, nucleophile or diene |
| Conditions | MeCN/H₂O, pH ≈ 10.5, 0 °C | THF, –20 to 25 °C, anhydrous | MeOH/H₂O or CH₂Cl₂, 25 °C |
| Stereochemistry | Spiro TS: high ee for trans- and trisubstituted alkenes | Predictable absolute configuration: hydride to the face set by the chiral boron-N framework | High ee: bulky group shields one iminium face |
| Rate / selectivity | Oxygen transfer from the dioxirane is rate-limiting | Hydride transfer is rate-limiting; catalyst turnover fast | Nucleophilic addition to the iminium is rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Shi epoxidation?
Chiral fructose-derived ketone (cat.), Oxone (KHSO₅), K₂CO₃ buffer. Conditions: MeCN/H₂O, pH ≈ 10.5, 0 °C.
Which bonds are formed and which are broken?
Formed: C–O ×2 (epoxide); dioxirane O–O. Broken: C=C π; peroxide O–O.
What is the stereochemical outcome?
Spiro TS: high ee for trans- and trisubstituted alkenes
What controls the rate or the selectivity?
Oxygen transfer from the dioxirane is rate-limiting
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam