Palladium-catalyzed coupling reactions

Sonogashira coupling reaction mechanism

Palladium compounds are used as a catalyst in many coupling reactions, usually as a homogeneous catalyst. Examples include:

• Negishi coupling between an organohalide and an organozinc compound
• Heck reaction between alkenes and aryl halides
• Suzuki reaction between aryl halides and boronic acids
• Stille reaction between organohalides and organotin compounds
• Hiyama coupling between organohalides and organosilicon compounds
• Sonogashira coupling between aryl halides and alkynes, with copper(I) iodide as a co-catalyst
• The Buchwald-Hartwig amination of an aryl halide with an amine
• The Kumada coupling of grignards and aryl or vinyl halides
• The Heck-Matsuda Reaction of an arenediazonium salt with an alkene

Typical palladium catalysts used include the following compounds:

• palladium acetate
• tetrakis(triphenylphosphine)palladium(0)
• bis(triphenylphosphine)palladium(II) dichloride
• [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride

Unoptimized reactions typically use 10-15 mol% of palladium; where optimized, catalyst loadings can be on the order of 0.1 mol % or below. Many exotic ligands and chiral catalysts have been reported, but they are largely not available commercially, and do not find widespread use. Much work is being done on replacing the phosphine ligands with other classes, such as Arduengo-type carbene complexes, as the phosphine ligands are typically oxygen sensitive (easily oxidized), and are labile (requiring additional free ligands).

With these reactions becoming ubiquitous, there has been interest in better techniques for removing the palladium catalyst. Metal scavengers such as SiliCycle's SiliaMetS, Smopex or resins such as QuadruPure and ISOLUTE promise more efficient separation than ordinary column chromatography.

In 2010, the Nobel Prize in Chemistry was awarded to Richard F. Heck, Ei-ichi Negishi and Akira Suzuki for their work on palladium-catalyzed cross couplings in organic synthesis.

See also

• Coupling reactions
• Transmetalation