Multicomponent — boronic acid Mannich
Petasis reaction
How the Petasis reaction 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: Amine (R₂NH), α-hydroxy aldehyde (glycolaldehyde, salicylaldehyde, glyoxylic acid), vinyl or aryl boronic acid. Conditions: EtOH, CH₂Cl₂ or HFIP, 25–80 °C; no added base or acid. Bonds formed: C–C (new, carbon–iminium); C–N; B–O (boric acid); bonds broken: C=O; C–B. Stereochemistry: Anti-aminoalcohols; α-hydroxyl directs facial selectivity (vinyl boronic acids retain E geometry). Rate and selectivity: Rate-limited by aryl transfer from the boronate; electron-rich/vinyl groups migrate fastest.
At a glance
Step 1: Iminium, then boronate complexation
An amine and an alpha-hydroxy aldehyde (or ketone) condense to form an iminium ion, with the nearby hydroxyl positioned to coordinate an incoming boron reagent.
Step 2: Aryl group migrates from boron to carbon
A vinyl or aryl boronic acid's organic group transfers to the iminium carbon in an intramolecular-flavored process, activated by that nearby hydroxyl bridging to boron — mechanistically a boron-mediated addition to the iminium, parallel to how a Grignard adds to a carbonyl.
Step 3: A substituted amine from three components
The product is a substituted amine bearing a new C–C bond — a mild, three-component alternative to the Mannich reaction that tolerates a broad range of functional groups since no strong base or strongly acidic conditions are needed.
Abbreviations and terms
- Ar
- Aryl group. Any aromatic ring substituent such as phenyl.
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- EtOH
- Ethanol. Polar protic solvent.
- TFE
- Fluorinated alcohols. Strongly H-bond-donating, non-nucleophilic solvents that stabilise cations.
- TS
- Transition state. The highest-energy point on the pathway between two minima; it cannot be isolated.
How it compares with related reactions
| Petasis reaction | Biginelli reaction | Bucherer-Bergs reaction | |
|---|---|---|---|
| Reagents | Amine (R₂NH), α-hydroxy aldehyde (glycolaldehyde, salicylaldehyde, glyoxylic acid), vinyl or aryl boronic acid | Aldehyde, urea, ethyl acetoacetate, HCl or Lewis acid | Ketone, KCN, (NH₄)₂CO₃ |
| Conditions | EtOH, CH₂Cl₂ or HFIP, 25–80 °C; no added base or acid | EtOH, reflux (or neat, 90 °C) | EtOH/H₂O, 60–70 °C (sealed vessel) |
| Stereochemistry | Anti-aminoalcohols; α-hydroxyl directs facial selectivity (vinyl boronic acids retain E geometry) | C4 stereocentre formed (racemic unless chiral acid catalyst) | Quaternary C5; racemic unless prochiral control |
| Rate / selectivity | Rate-limited by aryl transfer from the boronate; electron-rich/vinyl groups migrate fastest | Iminium formation or its Mannich-type capture is rate-limiting | Cyanide addition and carbamate cyclization are fast in the buffered medium |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Petasis reaction?
Amine (R₂NH), α-hydroxy aldehyde (glycolaldehyde, salicylaldehyde, glyoxylic acid), vinyl or aryl boronic acid. Conditions: EtOH, CH₂Cl₂ or HFIP, 25–80 °C; no added base or acid.
Which bonds are formed and which are broken?
Formed: C–C (new, carbon–iminium); C–N; B–O (boric acid). Broken: C=O; C–B.
What is the stereochemical outcome?
Anti-aminoalcohols; α-hydroxyl directs facial selectivity (vinyl boronic acids retain E geometry)
What controls the rate or the selectivity?
Rate-limited by aryl transfer from the boronate; electron-rich/vinyl groups migrate fastest
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam