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Also known as: Sonogashira-Hagihara Coupling
Discovered by Kenkichi Sonogashira (1975)
Palladium/copper co-catalyzed coupling of a terminal alkyne with an aryl halide. The copper acetylide intermediate undergoes transmetalation with the palladium complex. Creates sp-sp² C-C bonds.
Oxidative addition: Pd(0) inserts into Ar-X.
Cu cycle: CuI and the amine base form a Cu(I) acetylide from the terminal alkyne (Cu-C≡CR).
Cu co-catalyst activates the terminal alkyne
Transmetalation: The Cu acetylide transfers the alkynyl group to Pd, replacing X.
Reductive elimination: Ar and C≡CR couple, regenerating Pd(0).
Iodobenzene + Phenylacetylene
Pd(PPh₃)₂Cl₂, CuI, Et₃N
Diphenylacetylene (tolane)
4-Iodoanisole + TMS-acetylene
Pd(PPh₃)₂Cl₂, CuI, iPr₂NH
4-(Trimethylsilylethynyl)anisole
The standard method for making aryl-alkyne bonds. Essential in pharmaceutical synthesis, molecular wires, and organic electronics.