Inorganic — asymmetric phase-transfer catalysis
Asymmetric phase-transfer catalysis
How the Asymmetric phase-transfer catalysis 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 cinchona-derived Q*⁺Br⁻ (1–10 mol%), 50% aq. KOH, glycine imine tBu ester, BnBr. Conditions: Toluene/CH₂Cl₂, 0 °C, vigorous stirring. Bonds formed: C–C (α-alkylation); bonds broken: α C–H; C–Br. Stereochemistry: High ee: chiral ion pair shields one enolate face. Rate and selectivity: Alkylation of the ion pair is rate-limiting.
At a glance
Step 1: Interfacial deprotonation; cation carries the enolate
A chiral quaternary ammonium salt (often cinchona-alkaloid-derived) shuttles a deprotonated enolate anion from the aqueous/solid base phase into the organic phase — the identical anion-shuttling logic as ordinary phase-transfer catalysis.
Step 2: Chiral cation shields one face
Because the chiral cation forms a tight, well-defined ion pair with the enolate, it shields one face of the anion far more effectively than the other, exactly as a chiral auxiliary or organocatalyst's steric bulk does elsewhere in this library.
Step 3: Alkylation from the open face
The shielded enolate reacts with an electrophile (commonly an alkyl halide, in an SN2 alkylation) selectively from its open face, giving an enantioenriched product — this lets a simple achiral base and a catalytic chiral salt replace what would otherwise require a stoichiometric chiral auxiliary.
Abbreviations and terms
- t-Bu
- tert-Butyl. –C(CH₃)₃, a bulky group.
- Ph
- Phenyl. –C₆H₅.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- KOH
- Potassium hydroxide. Strong aqueous/alcoholic base.
- SN2
- Bimolecular nucleophilic substitution. One concerted step with backside attack and inversion; rate = k[RX][Nu].
- ee
- Enantiomeric excess. How much more of one enantiomer than the other is present.
How it compares with related reactions
| Asymmetric phase-transfer catalysis | Phase-transfer catalysis (anion shuttle) | Crabtree hydrogenation | |
|---|---|---|---|
| Reagents | Chiral cinchona-derived Q*⁺Br⁻ (1–10 mol%), 50% aq. KOH, glycine imine tBu ester, BnBr | Q⁺X⁻ (e.g. Bu₄N⁺Br⁻, 1–10 mol%), NaCN (aq), alkyl bromide (organic) | [Ir(cod)(PCy₃)(py)]⁺ PF₆⁻, H₂ (1 atm) |
| Conditions | Toluene/CH₂Cl₂, 0 °C, vigorous stirring | Biphasic H₂O / toluene, 25–80 °C, vigorous stirring | CH₂Cl₂, 25 °C |
| Stereochemistry | High ee: chiral ion pair shields one enolate face | SN2 inversion where applicable | Face selectivity set by the directing OH |
| Rate / selectivity | Alkylation of the ion pair is rate-limiting | Interfacial anion exchange and SN2 in organic phase | 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 Asymmetric phase-transfer catalysis?
Chiral cinchona-derived Q*⁺Br⁻ (1–10 mol%), 50% aq. KOH, glycine imine tBu ester, BnBr. Conditions: Toluene/CH₂Cl₂, 0 °C, vigorous stirring.
Which bonds are formed and which are broken?
Formed: C–C (α-alkylation). Broken: α C–H; C–Br.
What is the stereochemical outcome?
High ee: chiral ion pair shields one enolate face
What controls the rate or the selectivity?
Alkylation of the ion pair 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