Inorganic — asymmetric π-allyl chemistry
Trost asymmetric allylic alkylation
How the Trost asymmetric allylic alkylation 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: Allylic acetate, soft nucleophile (dimethyl malonate, BSA/KOAc), Pd₂(dba)₃ or [Pd(allyl)Cl]₂, chiral bisphosphine ligand L* (Trost ligand). Conditions: CH₂Cl₂ or THF, 25 °C. Bonds formed: C–C (new stereocentre); Pd–allyl (temporary); bonds broken: C–OAc. Stereochemistry: Ligand pocket selects the face and terminus attacked: high ee. Rate and selectivity: Oxidative ionisation or nucleophilic attack can be rate-limiting; fast enantiodetermining attack.
At a glance
Step 1: Ionisation to the π-allyl complex
A chiral bisphosphine ligand on Pd(0) oxidatively adds an allylic substrate, forming the same symmetric π-allyl palladium intermediate as the ordinary Tsuji-Trost reaction — but now held within a well-defined chiral pocket set by the ligand's shape.
Step 2: The chiral pocket picks a face
The chiral ligand environment makes one face (and often one terminus) of the π-allyl system substantially more accessible to an incoming nucleophile than the other — the identical facial-blocking strategy used by every other asymmetric catalyst in this library, just applied to an allyl-metal intermediate instead of a carbonyl or alkene.
Step 3: Enantioenriched allylic product
The nucleophile attacks the favored position, releasing an enantioenriched allylic product — this extension of the ordinary Tsuji-Trost mechanism with a chiral ligand is one of the most general, reliable ways to install a new stereocenter at an allylic position.
Abbreviations and terms
- L
- Ligand. A Lewis-base group (often a phosphine) bound to a metal centre.
- Ph
- Phenyl. –C₆H₅.
- OAc
- Acetoxy. –OC(=O)CH₃, an acetate group.
- THF
- Tetrahydrofuran. Cyclic ether solvent; its oxygen lone pairs solvate Li⁺/Mg²⁺ so organometallics stay dissolved and reactive.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- Pd2(dba)3
- Tris(dibenzylideneacetone)dipalladium(0). Air-stable source of Pd(0).
- dba
- Dibenzylideneacetone. Weakly bound alkene ligand on Pd(0).
- SN2
- Bimolecular nucleophilic substitution. One concerted step with backside attack and inversion; rate = k[RX][Nu].
- SN2′
- SN2-prime (allylic). Nucleophile attacks the alkene terminus with allylic transposition.
- ee
- Enantiomeric excess. How much more of one enantiomer than the other is present.
How it compares with related reactions
| Trost asymmetric allylic alkylation | Tsuji-Trost allylic substitution | Associative ligand substitution at a square-planar Pt(II) complex | |
|---|---|---|---|
| Reagents | Allylic acetate, soft nucleophile (dimethyl malonate, BSA/KOAc), Pd₂(dba)₃ or [Pd(allyl)Cl]₂, chiral bisphosphine ligand L* (Trost ligand) | allylic acetate/carbonate, soft Nu–H (e.g. dimethyl malonate), base, cat. Pd(PPh₃)₄ | K₂[PtCl₄] + NH₃ (aq) |
| Conditions | CH₂Cl₂ or THF, 25 °C | THF, 25–65 °C | H₂O, 25 °C |
| Stereochemistry | Ligand pocket selects the face and terminus attacked: high ee | Soft Nu: net retention (inversion at ionisation + inversion at attack) | Trigonal-bipyramidal intermediate; retention of geometry |
| Rate / selectivity | Oxidative ionisation or nucleophilic attack can be rate-limiting; fast enantiodetermining attack | Ionisation to the π-allyl complex is usually rate-limiting | Rate = k₁[Pt] + k₂[Pt][NH₃] (associative; entering-ligand dependent) |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Trost asymmetric allylic alkylation?
Allylic acetate, soft nucleophile (dimethyl malonate, BSA/KOAc), Pd₂(dba)₃ or [Pd(allyl)Cl]₂, chiral bisphosphine ligand L* (Trost ligand). Conditions: CH₂Cl₂ or THF, 25 °C.
Which bonds are formed and which are broken?
Formed: C–C (new stereocentre); Pd–allyl (temporary). Broken: C–OAc.
What is the stereochemical outcome?
Ligand pocket selects the face and terminus attacked: high ee
What controls the rate or the selectivity?
Oxidative ionisation or nucleophilic attack can be rate-limiting; fast enantiodetermining attack
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam