Inorganic — asymmetric catalysis
Sharpless asymmetric dihydroxylation
How the Sharpless asymmetric dihydroxylation 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: OsO₄ (cat.), (DHQ)₂PHAL / (DHQD)₂PHAL, K₃Fe(CN)₆ or NMO, K₂CO₃ (AD-mix α/β). Conditions: tBuOH/H₂O 1:1, 0 °C. Bonds formed: 2 C–O (cis diol); bonds broken: C=C π; Os=O π. Stereochemistry: Syn addition; ligand chooses the face (AD-mix α vs β). Rate and selectivity: Ligand-accelerated; hydrolysis of the osmate ester releases product.
At a glance
Step 1: Concerted [3+2] with OsO₄·L*
An OsO₄–chiral ligand complex approaches the alkene; the alkene's π electrons attack osmium in a concerted [3+2] cycloaddition, forming a five-membered cyclic osmate ester across both alkene carbons at once.
Step 2: The ligand blocks one face
The chiral amine ligand (from a cinchona alkaloid) bound to osmium blocks one face of the alkene, so only the exposed face reacts — the same organizational strategy as Sharpless epoxidation, just with a different metal and a [3+2] instead of oxygen transfer.
Step 3: Hydrolysis and reoxidation
Hydrolysis of the osmate ester releases the enantioenriched 1,2-diol and regenerates OsO₄, which is reoxidized by a stoichiometric co-oxidant to continue the catalytic cycle.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- L
- Ligand. A Lewis-base group (often a phosphine) bound to a metal centre.
- K2CO3
- Potassium carbonate. Mild inorganic base.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- OsO4
- Osmium tetroxide. Adds syn across alkenes to give diols (via a cyclic osmate ester).
- NMO
- N-Methylmorpholine N-oxide. Co-oxidant that reoxidises Os(VI) to Os(VIII).
How it compares with related reactions
| Sharpless asymmetric dihydroxylation | Asymmetric phase-transfer catalysis | Crabtree hydrogenation | |
|---|---|---|---|
| Reagents | OsO₄ (cat.), (DHQ)₂PHAL / (DHQD)₂PHAL, K₃Fe(CN)₆ or NMO, K₂CO₃ (AD-mix α/β) | 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 | tBuOH/H₂O 1:1, 0 °C | Toluene/CH₂Cl₂, 0 °C, vigorous stirring | CH₂Cl₂, 25 °C |
| Stereochemistry | Syn addition; ligand chooses the face (AD-mix α vs β) | High ee: chiral ion pair shields one enolate face | Face selectivity set by the directing OH |
| Rate / selectivity | Ligand-accelerated; hydrolysis of the osmate ester releases product | 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 dihydroxylation?
OsO₄ (cat.), (DHQ)₂PHAL / (DHQD)₂PHAL, K₃Fe(CN)₆ or NMO, K₂CO₃ (AD-mix α/β). Conditions: tBuOH/H₂O 1:1, 0 °C.
Which bonds are formed and which are broken?
Formed: 2 C–O (cis diol). Broken: C=C π; Os=O π.
What is the stereochemical outcome?
Syn addition; ligand chooses the face (AD-mix α vs β)
What controls the rate or the selectivity?
Ligand-accelerated; hydrolysis of the osmate ester releases product
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam