Lewis-acid-catalyzed allylation
Sakurai-Hosomi allylation
How the Sakurai-Hosomi allylation 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: Allyltrimethylsilane, aldehyde or ketone, TiCl₄ (or BF₃·OEt₂). Conditions: CH₂Cl₂, –78 °C → 0 °C; aqueous workup. Bonds formed: C–C (γ-carbon of allylsilane to C=O carbon); C=C shifted; Si–Cl; bonds broken: C=O π; C–Si; allyl C=C π (moved). Stereochemistry: Open (acyclic) TS; allyl terminus attacks, product alkene transposed. Rate and selectivity: Lewis-acid activation of C=O makes addition fast even at –78 °C.
At a glance
Step 1: TiCl₄ activates the carbonyl
A Lewis acid (like TiCl₄) coordinates a carbonyl oxygen, activating the carbon toward nucleophilic attack — the same Lewis-acid activation strategy as Mukaiyama aldol.
Step 2: Allylsilane π bond attacks (β-silyl cation)
An allylsilane's alkene attacks the activated carbonyl carbon through its π electrons, with the developing positive charge stabilized specifically at the carbon bearing silicon — the β-silicon effect, where an adjacent C–Si bond hyperconjugatively stabilizes cationic character.
Step 3: Loss of the silyl group
Loss of the silyl group (captured by the departing alkoxide or an external nucleophile) delivers a homoallylic alcohol with the double bond transposed — the allyl group has migrated one carbon over, a signature of this addition-elimination pathway.
Abbreviations and terms
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- Lewis acid
- Lewis acid. Electron-pair acceptor (AlCl₃, BF₃, TiCl₄…) that activates carbonyls and halides.
- BF3
- Boron trifluoride. Lewis acid (usually as the Et₂O complex).
- TiCl4
- Titanium tetrachloride. Strong, oxophilic Lewis acid that chelates carbonyls.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
- LUMO
- Lowest unoccupied molecular orbital. The orbital that accepts electrons in a reaction.
How it compares with related reactions
| Sakurai-Hosomi allylation | Mukaiyama aldol reaction | Mukaiyama-Michael reaction | |
|---|---|---|---|
| Reagents | Allyltrimethylsilane, aldehyde or ketone, TiCl₄ (or BF₃·OEt₂) | Silyl enol ether, aldehyde, TiCl₄ (or BF₃·OEt₂, Sc(OTf)₃) | Silyl enol ether, α,β-unsaturated ketone, TiCl₄ (or other Lewis acid) |
| Conditions | CH₂Cl₂, –78 °C → 0 °C; aqueous workup | CH₂Cl₂, –78 °C; aqueous work-up | CH₂Cl₂, –78 °C; aqueous workup |
| Stereochemistry | Open (acyclic) TS; allyl terminus attacks, product alkene transposed | Open TS; syn/anti set by enol geometry and Lewis acid; chiral LAs give ee | Enol-ether geometry and Lewis acid control syn/anti; new stereocentres possible |
| Rate / selectivity | Lewis-acid activation of C=O makes addition fast even at –78 °C | Lewis-acid activation of the aldehyde is essential | Lewis acid binding to the enone drives the conjugate addition |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Sakurai-Hosomi allylation?
Allyltrimethylsilane, aldehyde or ketone, TiCl₄ (or BF₃·OEt₂). Conditions: CH₂Cl₂, –78 °C → 0 °C; aqueous workup.
Which bonds are formed and which are broken?
Formed: C–C (γ-carbon of allylsilane to C=O carbon); C=C shifted; Si–Cl. Broken: C=O π; C–Si; allyl C=C π (moved).
What is the stereochemical outcome?
Open (acyclic) TS; allyl terminus attacks, product alkene transposed
What controls the rate or the selectivity?
Lewis-acid activation of C=O makes addition fast even at –78 °C
Study guides that help with this reaction
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go