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Inorganic — Pd/norbornene relay

Catellani reaction

How the Catellani reaction works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.

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In short. A 3-step mechanism. Typical reagents: ArI, norbornene (NBE), R–X (ortho electrophile), terminating partner (e.g. ArB(OH)₂), cat. Pd(OAc)₂/PPh₃, K₂CO₃. Conditions: DMF or MeCN, 80–105 °C. Bonds formed: ortho C–C and ipso C–C bonds; bonds broken: C–I, ortho C–H. Stereochemistry: NBE exo-insertion; achiral product. Rate and selectivity: Ortho C–H palladation (CMD) after NBE insertion is key.

At a glance

ReagentsArI, norbornene (NBE), R–X (ortho electrophile), terminating partner (e.g. ArB(OH)₂), cat. Pd(OAc)₂/PPh₃, K₂CO₃
Solvent / conditionsDMF or MeCN, 80–105 °C
Bonds formedortho C–C and ipso C–C bonds
Bonds brokenC–I, ortho C–H
StereochemistryNBE exo-insertion; achiral product
Rate / selectivityOrtho C–H palladation (CMD) after NBE insertion is key

Step 1: Oxidative addition, NBE insertion

+insertionPd(II)LIPd(II)LI1 · OXIDATIVE ADDITION, NBE INSERTIONaryl–Pd–I (after Pd(0) + ArI)C₇H₇IPdINTERMEDIATEnorborneneC₇H₁₀SUBSTRATEalkyl–Pd(II)C₁₄H₁₇IPdINTERMEDIATESyn migratory insertion: aryl and Pd add to the same face of NBE.

Pd(0) oxidatively adds an aryl halide, and norbornene inserts into the resulting Ar–Pd bond via migratory insertion — the same insertion step used throughout this library, giving an alkyl-Pd(II) intermediate with the aryl group now on the norbornane and Pd on the adjacent carbon.

Step 2: Palladacycle, then ortho-functionalisation

ortho C–H act.base, −HICH₃IPd(IV), red. elim.Pd(II)LIPd(II)LPdPd(II)LI2 · PALLADACYCLE, THEN ORTHO-FUNCTIONALISATIONalkyl–Pd(II)C₁₄H₁₇IPdINTERMEDIATEfive-membered palladacycleC₁₄H₁₆PdINTERMEDIATEpalladacycleC₁₄H₁₆PdINTERMEDIATEortho-methylated alkyl–PdC₁₅H₁₉IPdINTERMEDIATEThe strained palladacycle is attacked by the external electrophile at the aryl–Pd carbon.

An intramolecular C–H activation (the same CMD-type step covered earlier) at the aryl's ortho position now closes a strained bicyclic palladacycle, which is functionalized with an external electrophile before norbornene de-inserts (a retro-migratory-insertion) and departs, regenerating Ar–Pd–X.

Step 3: NBE extrusion, ipso termination

retro-insertionNBE leaves++transmetalationred. elimination+Pd(II)LIPdIPdIRBOHOHRPd3 · NBE EXTRUSION, IPSO TERMINATIONortho-methylated alkyl–PdC₁₅H₁₉IPdINTERMEDIATEaryl–Pd–IC₈H₉IPdINTERMEDIATEnorborneneC₇H₁₀CATALYSTaryl–Pd–IC₈H₉IPdINTERMEDIATER–B(OH)₂NUCLEOPHILE1,2,3-trisubstituted arenePRODUCTPd(0)LCATALYSTNBE is a temporary relay: ortho and ipso functionalised in one cycle.

Finally, a standard cross-coupling termination step (like Suzuki-type transmetalation and reductive elimination) installs a group at the original ipso position — norbornene's temporary role as a relay lets this sequence install substituents at both the ortho and ipso positions of one arene in a single catalytic cycle.

Abbreviations and terms

R
R group. Any carbon substituent (alkyl, aryl…) whose identity does not matter for the mechanism.
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.
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.
K2CO3
Potassium carbonate. Mild inorganic base.
PPh3
Triphenylphosphine. Nucleophilic phosphine; forms very strong P=O bonds, driving Wittig, Appel and Mitsunobu reactions.
Pd(OAc)2
Palladium(II) acetate. Pd(II) pre-catalyst, reduced in situ to Pd(0).
CMD
Concerted metalation–deprotonation. C–H activation where a carboxylate shuttles the proton as the C–M bond forms.

How it compares with related reactions

Catellani reactionAssociative ligand substitution at a square-planar Pt(II) complexAsymmetric phase-transfer catalysis
ReagentsArI, norbornene (NBE), R–X (ortho electrophile), terminating partner (e.g. ArB(OH)₂), cat. Pd(OAc)₂/PPh₃, K₂CO₃K₂[PtCl₄] + NH₃ (aq)Chiral cinchona-derived Q*⁺Br⁻ (1–10 mol%), 50% aq. KOH, glycine imine tBu ester, BnBr
ConditionsDMF or MeCN, 80–105 °CH₂O, 25 °CToluene/CH₂Cl₂, 0 °C, vigorous stirring
StereochemistryNBE exo-insertion; achiral productTrigonal-bipyramidal intermediate; retention of geometryHigh ee: chiral ion pair shields one enolate face
Rate / selectivityOrtho C–H palladation (CMD) after NBE insertion is keyRate = k₁[Pt] + k₂[Pt][NH₃] (associative; entering-ligand dependent)Alkylation of the ion pair is rate-limiting

Test yourself

Try to answer each question before opening it.

Which reagents and conditions are typical for the Catellani reaction?

ArI, norbornene (NBE), R–X (ortho electrophile), terminating partner (e.g. ArB(OH)₂), cat. Pd(OAc)₂/PPh₃, K₂CO₃. Conditions: DMF or MeCN, 80–105 °C.

Which bonds are formed and which are broken?

Formed: ortho C–C and ipso C–C bonds. Broken: C–I, ortho C–H.

What is the stereochemical outcome?

NBE exo-insertion; achiral product

What controls the rate or the selectivity?

Ortho C–H palladation (CMD) after NBE insertion is key

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