Boron — stereospecific homologation
Matteson homologation
How the Matteson homologation 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: R–B(OR′)₂, LiCHCl₂ (from CH₂Cl₂ + LDA or n-BuLi), then ZnCl₂ (cat.); R″MgX for next step. Conditions: THF, −100 → 25 °C. Bonds formed: C–C (R migrates to carbon), α-chloro boronic ester; bonds broken: B–C(R), C–Cl. Stereochemistry: R migrates with retention; the new CHCl carbon is set with inversion at Cl displacement. Rate and selectivity: ZnCl₂ accelerates 1,2-shift; chiral diols (pinanediol) give >99:1 d.r..
At a glance
Step 1: Carbenoid adds to boron: ate complex
A boronic ester reacts with lithiated dichloromethane, and the resulting carbanion coordinates to boron's empty p-orbital, forming an unstable, electron-rich ate complex with a good leaving group (chloride) positioned nearby.
Step 2: 1,2-Shift displaces chloride
One of the boronic ester's carbon substituents migrates from boron directly onto the adjacent carbanion carbon in a concerted 1,2-shift, displacing chloride — the same migration logic used throughout this library's rearrangement family, just at boron instead of carbon or nitrogen.
Step 3: One carbon longer
The result is a new boronic ester, extended by one carbon, with the stereochemistry at the migrating carbon fully inverted and predictable — this homologation is prized specifically because it's stereospecific, letting chemists build complex, stereodefined carbon chains one carbon at a time.
Abbreviations and terms
- R
- R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
- 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.
- LDA
- Lithium diisopropylamide. Strong (pKa ≈ 36), bulky, non-nucleophilic base that makes kinetic enolates quantitatively.
- n-BuLi
- n-Butyllithium. Very strong base/nucleophile (pKa of butane ≈ 50); deprotonates alkynes and does lithium–halogen exchange.
- SN2
- Bimolecular nucleophilic substitution. One concerted step with backside attack and inversion; rate = k[RX][Nu].
How it compares with related reactions
| Matteson homologation | Zweifel olefination | CBS reduction (Corey-Bakshi-Shibata) | |
|---|---|---|---|
| Reagents | R–B(OR′)₂, LiCHCl₂ (from CH₂Cl₂ + LDA or n-BuLi), then ZnCl₂ (cat.); R″MgX for next step | alkenyl–B(OR)₂, R′Li, I₂, NaOMe (or NaOH) | (S)- or (R)-Me-CBS oxazaborolidine (5–10 mol%), BH₃·THF or BH₃·SMe₂ |
| Conditions | THF, −100 → 25 °C | THF, −78 → 25 °C | THF, –20 to 25 °C, anhydrous |
| Stereochemistry | R migrates with retention; the new CHCl carbon is set with inversion at Cl displacement | Net inversion of alkene geometry (E-boronate → Z-alkene) | Predictable absolute configuration: hydride to the face set by the chiral boron-N framework |
| Rate / selectivity | ZnCl₂ accelerates 1,2-shift; chiral diols (pinanediol) give >99:1 d.r. | Iodonium formation fast; anti-elimination fast with base | Hydride transfer is rate-limiting; catalyst turnover fast |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Matteson homologation?
R–B(OR′)₂, LiCHCl₂ (from CH₂Cl₂ + LDA or n-BuLi), then ZnCl₂ (cat.); R″MgX for next step. Conditions: THF, −100 → 25 °C.
Which bonds are formed and which are broken?
Formed: C–C (R migrates to carbon), α-chloro boronic ester. Broken: B–C(R), C–Cl.
What is the stereochemical outcome?
R migrates with retention; the new CHCl carbon is set with inversion at Cl displacement
What controls the rate or the selectivity?
ZnCl₂ accelerates 1,2-shift; chiral diols (pinanediol) give >99:1 d.r.
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam