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Also known as: Mizoroki-Heck Reaction
Discovered by Tsutomu Mizoroki, Richard Heck (1972)
Palladium-catalyzed coupling of an aryl halide with an alkene. Unlike Suzuki, the alkene partner is used directly (no organometallic needed). Produces substituted alkenes with high E-selectivity. Nobel Prize 2010.
Oxidative addition: Pd(0) inserts into Ar-X bond.
Syn migratory insertion: The alkene coordinates to Pd, then the Ar group migrates to the alkene in a syn fashion.
Syn insertion determines regiochemistry
β-Hydride elimination: Pd and a β-H eliminate in a syn fashion to give the alkene product and H-Pd-X.
Syn elimination — gives E-alkene preferentially
Base regenerates Pd(0) by removing HX from H-Pd-X.
Catalytic cycle closed
Iodobenzene + Methyl acrylate
Pd(OAc)₂, Et₃N, DMF, 100°C
Methyl (E)-cinnamate
Bromobenzene + Styrene
Pd(PPh₃)₄, Et₃N, DMF
(E)-Stilbene
Powerful method for making substituted alkenes. Intramolecular version is a key strategy for natural product synthesis.