Inorganic — asymmetric catalysis
Sharpless asymmetric epoxidation
How the Sharpless asymmetric 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: Ti(OiPr)₄ (cat.), (+)- or (–)-DET/DIPT, tBuOOH. Conditions: CH₂Cl₂, –20 °C, 3 Å molecular sieves. Bonds formed: 2 C–O (epoxide); Ti–OtBu; bonds broken: O–O (peroxide); Ti–OiPr. Stereochemistry: Tartrate enantiomer dictates the epoxidised face; allylic OH required. Rate and selectivity: Ligand-accelerated; 80–95% yield, >90% ee typical.
At a glance
Step 1: Ti binds alcohol and hydroperoxide
A titanium(IV) tartrate complex binds both the allylic alcohol substrate (through its oxygen) and tert-butyl hydroperoxide (through its oxygen) simultaneously, holding both reactive groups in a well-defined chiral pocket.
Step 2: Oxygen transfer to one alkene face
With both partners held rigidly by the same metal center, oxygen transfers directly from the peroxide to the alkene face that the chiral tartrate ligand makes accessible — the titanium's role is purely organizational, positioning the substrate for facially selective attack.
Step 3: One enantiomer of the epoxy alcohol
The alkene face reacted upon is fully predictable from which tartrate enantiomer (natural or unnatural) is used — this single method reliably gave synthetic chemists access to enantiopure epoxides for the first time and won its inventor a share of the 2001 Nobel Prize.
Abbreviations and terms
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- 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
| Sharpless asymmetric epoxidation | Asymmetric phase-transfer catalysis | Crabtree hydrogenation | |
|---|---|---|---|
| Reagents | Ti(OiPr)₄ (cat.), (+)- or (–)-DET/DIPT, tBuOOH | Chiral cinchona-derived Q*⁺Br⁻ (1–10 mol%), 50% aq. KOH, glycine imine tBu ester, BnBr | [Ir(cod)(PCy₃)(py)]⁺ PF₆⁻, H₂ (1 atm) |
| Conditions | CH₂Cl₂, –20 °C, 3 Å molecular sieves | Toluene/CH₂Cl₂, 0 °C, vigorous stirring | CH₂Cl₂, 25 °C |
| Stereochemistry | Tartrate enantiomer dictates the epoxidised face; allylic OH required | High ee: chiral ion pair shields one enolate face | Face selectivity set by the directing OH |
| Rate / selectivity | Ligand-accelerated; 80–95% yield, >90% ee typical | Alkylation of the ion pair is rate-limiting | Alkene insertion/oxidative addition; works for tetrasubstituted alkenes |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Sharpless asymmetric epoxidation?
Ti(OiPr)₄ (cat.), (+)- or (–)-DET/DIPT, tBuOOH. Conditions: CH₂Cl₂, –20 °C, 3 Å molecular sieves.
Which bonds are formed and which are broken?
Formed: 2 C–O (epoxide); Ti–OtBu. Broken: O–O (peroxide); Ti–OiPr.
What is the stereochemical outcome?
Tartrate enantiomer dictates the epoxidised face; allylic OH required
What controls the rate or the selectivity?
Ligand-accelerated; 80–95% yield, >90% ee typical
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam