Inorganic — concerted outer-sphere hydrogenation
Noyori asymmetric transfer hydrogenation
How the Noyori asymmetric transfer hydrogenation 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: RuCl[(S,S)-TsDPEN](p-cymene) (0.5–2 mol%), iPrOH/KOH or HCO₂H/Et₃N. Conditions: 25–40 °C. Bonds formed: C–H; O–H; bonds broken: Ru–H; N–H; C=O π. Stereochemistry: High ee; CH/π interaction of arene with substrate in the TS. Rate and selectivity: Concerted H₂ transfer is rate-limiting.
At a glance
Step 1: Donor regenerates the Ru–H / N–H catalyst
A chiral Ru(II) complex bearing both an N–H-containing ligand and a hydride, generated from a hydrogen donor like isopropanol or formic acid, positions the ketone substrate's carbonyl near both the metal hydride and the ligand's N–H proton simultaneously.
Step 2: Concerted hydride + proton transfer (outer sphere)
Hydride and proton transfer to the substrate's carbon and oxygen simultaneously, in a concerted, six-membered pericyclic-like transition state — crucially, the substrate never directly bonds to the metal at all, unlike Noyori's own H₂-based hydrogenation covered earlier.
Step 3: Alcohol released, catalyst re-armed
This outer-sphere mechanism (metal-ligand bifunctional catalysis) releases the enantioenriched alcohol and regenerates the Ru–H/N–H catalyst from the hydrogen-donor solvent — avoiding substrate coordination entirely is what allows this method to tolerate substrates that would poison or bind too strongly to conventional inner-sphere hydrogenation catalysts.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- Ar
- Aryl group. Any aromatic ring substituent such as phenyl.
- Ph
- Phenyl. –C₆H₅.
- Ts
- Tosyl. p-Toluenesulfonyl (p-CH₃C₆H₄SO₂–).
- Et3N
- Triethylamine. Common tertiary-amine base that scavenges HCl.
- KOH
- Potassium hydroxide. Strong aqueous/alcoholic base.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- RE
- Reductive elimination. Two groups on a metal couple and leave, lowering the oxidation state by two.
- ee
- Enantiomeric excess. How much more of one enantiomer than the other is present.
How it compares with related reactions
| Noyori asymmetric transfer hydrogenation | Associative ligand substitution at a square-planar Pt(II) complex | Asymmetric phase-transfer catalysis | |
|---|---|---|---|
| Reagents | RuCl[(S,S)-TsDPEN](p-cymene) (0.5–2 mol%), iPrOH/KOH or HCO₂H/Et₃N | K₂[PtCl₄] + NH₃ (aq) | Chiral cinchona-derived Q*⁺Br⁻ (1–10 mol%), 50% aq. KOH, glycine imine tBu ester, BnBr |
| Conditions | 25–40 °C | H₂O, 25 °C | Toluene/CH₂Cl₂, 0 °C, vigorous stirring |
| Stereochemistry | High ee; CH/π interaction of arene with substrate in the TS | Trigonal-bipyramidal intermediate; retention of geometry | High ee: chiral ion pair shields one enolate face |
| Rate / selectivity | Concerted H₂ transfer is rate-limiting | Rate = k₁[Pt] + k₂[Pt][NH₃] (associative; entering-ligand dependent) | Alkylation of the ion pair is rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Noyori asymmetric transfer hydrogenation?
RuCl[(S,S)-TsDPEN](p-cymene) (0.5–2 mol%), iPrOH/KOH or HCO₂H/Et₃N. Conditions: 25–40 °C.
Which bonds are formed and which are broken?
Formed: C–H; O–H. Broken: Ru–H; N–H; C=O π.
What is the stereochemical outcome?
High ee; CH/π interaction of arene with substrate in the TS
What controls the rate or the selectivity?
Concerted H₂ transfer 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