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OxidationAdvancedNobel Prize 1980
Sharpless Asymmetric Epoxidation
Also known as: SAE, Sharpless Epoxidation
Discovered by K. Barry Sharpless (1980)
General Equation
Allylic alcohol + TBHP → Epoxy alcohol (>90% ee)
Description
Enantioselective epoxidation of allylic alcohols using Ti(OiPr)₄, a tartrate ester ligand, and TBHP as oxidant. The mnemonic: draw the allylic alcohol with OH in the lower right — L-(+)-DIPT delivers oxygen from the top, D-(-)-DIPT from the bottom. Nobel Prize 2001.
Reaction Scheme
Reactants:
- • Allylic alcohol
Products:
- • Enantioenriched 2,3-epoxy alcohol (>90% ee)
Reagents:
- • Ti(OiPr)₄ (titanium tetraisopropoxide)
- • TBHP (tert-butyl hydroperoxide)
- • DET or DIPT (chiral tartrate ligand)
Conditions:
- • CH₂Cl₂, -20°C, molecular sieves
Mechanism (2 steps)
1
Ti(OiPr)₄ exchanges two isopropoxide ligands with the tartrate (DET/DIPT) and the allylic alcohol, forming a chiral Ti-peroxo complex.
Arrow: curvedChiral Ti-peroxo complex
Allylic alcohol coordinates to Ti — substrate must have OH
2
The peroxide oxygen is delivered to one specific face of the alkene (determined by the tartrate chirality), forming the epoxide enantioselectively.
Arrow: curved
L-tartrate → top face; D-tartrate → bottom face (mnemonic)
Key Points to Remember
- ✓Only works with allylic alcohols (OH required for Ti coordination)
- ✓Mnemonic: draw OH at lower right → L-(+)-DET attacks from top, D-(-)-DET from bottom
- ✓Typically >90% ee (often >95% ee)
- ✓Catalytic with molecular sieves (removes water)
- ✓Kinetic resolution: racemic allylic alcohols → one enantiomer epoxidized selectively
- ✓K. Barry Sharpless — Nobel Prize 2001 (also 2022 for click chemistry!)
Examples
Reactant:
Geraniol (E-allylic alcohol)
Reagent:
Ti(OiPr)₄, L-(+)-DET, TBHP, -20°C
Product:
(2S,3S)-2,3-Epoxygeraniol
Yield: 90%, 95% ee
Reactant:
(E)-2-Buten-1-ol
Reagent:
Ti(OiPr)₄, D-(-)-DIPT, TBHP
Product:
(2S,3S)-Epoxybutan-1-ol
Yield: 85%, 93% ee
Synthetic Utility
First practical catalytic asymmetric synthesis. Epoxy alcohols are extremely versatile intermediates for total synthesis. Changed the field of asymmetric catalysis.
Limitations
- ⚠Only allylic alcohols (not simple alkenes)
- ⚠For non-allylic alkenes: use Jacobsen epoxidation (Mn-salen) or Shi epoxidation
- ⚠Sensitive to moisture (need molecular sieves)
#asymmetric#epoxidation#Nobel#ee#Sharpless#enantioselective