Pd-catalyzed cross-coupling
Heck reaction: full catalytic cycle
How the Heck 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: ArBr, alkene (e.g. methyl acrylate), Pd(OAc)₂/PPh₃, Et₃N. Conditions: DMF or MeCN, 80–120 °C. Bonds formed: Ar–C(sp²); new C=C (shifted); bonds broken: Ar–Br; vinylic C–H. Stereochemistry: Syn insertion, syn β-H elimination; E-alkene favoured. Rate and selectivity: Aryl adds to the less hindered alkene carbon.
At a glance
Step 1: Oxidative addition
Pd(0) oxidatively adds an aryl halide, forming Ar–Pd(II)–X.
Step 2: Coordination and migratory insertion
The alkene coordinates to palladium, then undergoes migratory insertion into the Ar–Pd bond, forming a new C–C bond and a Pd-alkyl species — the same insertion step from Wilkinson's cycle, now forming a bond to an aryl group instead of hydrogen.
Step 3: β-H elimination, base regenerates Pd(0)
β-hydride elimination releases the substituted alkene product and forms a Pd–H species; loss of HX regenerates active Pd(0) — this sequence installs an aryl or vinyl group directly onto an alkene with a new double bond in place.
Abbreviations and terms
- Ar
- Aryl group. Any aromatic ring substituent such as phenyl.
- X
- Halogen / leaving group. Cl, Br or I (sometimes any leaving group).
- 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.
- DMF
- N,N-Dimethylformamide. Polar aprotic solvent – dissolves ionic nucleophiles but does not H-bond to them, speeding SN2 and SNAr.
- MeCN
- Acetonitrile. Polar aprotic solvent.
- Et3N
- Triethylamine. Common tertiary-amine base that scavenges HCl.
- PPh3
- Triphenylphosphine. Nucleophilic phosphine; forms very strong P=O bonds, driving Wittig, Appel and Mitsunobu reactions.
- HBr
- Hydrobromic acid. Strong acid; bromide is a good nucleophile.
- Pd(OAc)2
- Palladium(II) acetate. Pd(II) pre-catalyst, reduced in situ to Pd(0).
- Wilkinson
- Wilkinson’s catalyst, RhCl(PPh₃)₃. Homogeneous hydrogenation catalyst.
- L2
- Ligand set. Spectator ligands on the metal that tune its reactivity.
How it compares with related reactions
| Heck reaction | Buchwald-Hartwig amination | Hiyama coupling | |
|---|---|---|---|
| Reagents | ArBr, alkene (e.g. methyl acrylate), Pd(OAc)₂/PPh₃, Et₃N | ArBr, R₂NH, Pd₂(dba)₃ / bulky phosphine (XPhos, BINAP), NaOtBu | ArX, Ar′Si(OMe)₃ (or ArSiF₃), Pd(0) cat., TBAF (F⁻ activator) |
| Conditions | DMF or MeCN, 80–120 °C | Toluene or dioxane, 80–110 °C | THF or DMF, 60–100 °C |
| Stereochemistry | Syn insertion, syn β-H elimination; E-alkene favoured | No new stereocentre; retention of aryl geometry | Retention at sp² carbons; E/Z alkenes preserved |
| Rate / selectivity | Aryl adds to the less hindered alkene carbon | Bulky, electron-rich ligand speeds oxidative addition and C–N reductive elimination | Transmetalation (needs F⁻ activation) is usually rate-limiting |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Heck reaction?
ArBr, alkene (e.g. methyl acrylate), Pd(OAc)₂/PPh₃, Et₃N. Conditions: DMF or MeCN, 80–120 °C.
Which bonds are formed and which are broken?
Formed: Ar–C(sp²); new C=C (shifted). Broken: Ar–Br; vinylic C–H.
What is the stereochemical outcome?
Syn insertion, syn β-H elimination; E-alkene favoured
What controls the rate or the selectivity?
Aryl adds to the less hindered alkene carbon
Study guides that help with this reaction
- How to learn reaction mechanisms (without memorising everything)
- How to answer mechanism questions in an exam