Palladium-catalyzed coupling reactions
Encyclopedia
Palladium compounds are used as a catalyst in many coupling reactions, usually as a homogeneous catalyst. Examples include:
Typical palladium catalysts used include the following compounds:
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 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.
- Heck reactionHeck reactionThe Heck reaction is the chemical reaction of an unsaturated halide with an alkene and a base and palladium catalyst to form a substituted alkene. Together with the other palladium-catalyzed cross-coupling reactions, this reaction is of great importance, as it allows one to do substitution...
between alkeneAlkeneIn organic chemistry, an alkene, olefin, or olefine is an unsaturated chemical compound containing at least one carbon-to-carbon double bond...
s and aryl halides - Suzuki reactionSuzuki reactionThe Suzuki reaction is the organic reaction of an aryl- or vinyl-boronic acid with an aryl- or vinyl-halide catalyzed by a palladium complex. It is widely used to synthesize poly-olefins, styrenes, and substituted biphenyls, and has been extended to incorporate alkyl bromides...
between aryl halides and boronic acids - Stille reactionStille reactionThe Stille reaction is a chemical reaction coupling an organotin compound with an sp2-hybridized organic halide catalyzed by palladium. The reaction is widely used in organic synthesis....
between organohalides and organotin compounds - Hiyama couplingHiyama couplingIn organic chemistry, a Hiyama coupling is a palladium or nickel-catalyzed cross coupling reaction of organosilanes with organic halides or triflates. Hiyama couplings were first reported by Yasuo Hatanaka and Tamejiro Hiyama in 1988....
between organohalides and organosilicon compounds - Sonogashira couplingSonogashira couplingIn organic chemistry, a Sonogashira coupling is a coupling reaction of terminal alkynes with aryl or vinyl halides. This reaction was first reported by Kenkichi Sonogashira and Nobue Hagihara in 1975.-Catalyst:...
between aryl halides and alkyneAlkyneAlkynes are hydrocarbons that have a triple bond between two carbon atoms, with the formula CnH2n-2. Alkynes are traditionally known as acetylenes, although the name acetylene also refers specifically to C2H2, known formally as ethyne using IUPAC nomenclature...
s, with copper(I) iodideCopper(I) iodideCopper iodide is the inorganic compound with the formula CuI. It is also known as cuprous iodide. It is useful in a variety of applications ranging from organic synthesis to cloud seeding....
as a co-catalyst - Negishi couplingNegishi couplingThe Negishi coupling is a cross coupling reaction in organic chemistry involving an organozinc compound, an organic halide and a nickel or palladium catalyst creating a new carbon-carbon covalent bond:* The halide X can be chloride, bromine or iodine but also a triflate or acetyloxy group with as...
between an organohalide and an organozinc compoundOrganozinc compoundOrganozinc compounds in organic chemistry contain carbon to zinc chemical bonds. Organozinc chemistry is the science of organozinc compounds describing their physical properties, synthesis and reactions.... - The Buchwald-Hartwig amination of an aryl halide with an amineAmineAmines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
- The Heck-Matsuda ReactionHeck-Matsuda reactionThe Heck-Matsuda reaction is an organic reaction and a type of palladium catalysed arylation of olefins that uses arenediazonium salts as an alternative to aryl halides and triflates...
of an arenediazonium salt with an alkene
Typical palladium catalysts used include the following compounds:
- palladium acetate
- tetrakis(triphenylphosphine)palladium(0)Tetrakis(triphenylphosphine)palladium(0)Tetrakispalladium is the chemical compound Pd[P3]4, often abbreviated Pd4, or even PdP4. It is a bright yellow crystalline solid that becomes brown upon decomposition in air.-Structure and properties:...
- bis(triphenylphosphine)palladium(II) dichlorideBis(triphenylphosphine)palladium(II) dichlorideBispalladium dichloride is a coordination compound of palladium containing two triphenylphosphine and two chloride ligands. This yellow complex is often used for palladium-catalyzed coupling reactions, e.g. the Sonogashira–Hagihara reaction. The complex is square planar...
- [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride(1,1'-Bis(diphenylphosphino)ferrocene)palladium(II) dichloride[1,1'-Bisferrocene]palladium dichloride is an palladium complex containing the iron-containing dppf ligand. Commercially available, this compound is popularly used for palladium-catalyzed coupling reactions....
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
Persistent carbene
A persistent carbene is a type of carbene demonstrating particular stability. The best-known examples are diaminocarbenes with the general formula 2C:, where the 'R's are various functional groups...
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 Smopex or resins such as QuadruPure and ISOLUTE promise more efficient separation than ordinary column chromatography
Column chromatography
Column chromatography in chemistry is a method used to purify individual chemical compounds from mixtures of compounds. It is often used for preparative applications on scales from micrograms up to kilograms.The main advantage of column chromatography is the relatively low cost and disposability...
.
In 2010, the Nobel Prize in Chemistry
Nobel Prize in Chemistry
The Nobel Prize in Chemistry is awarded annually by the Royal Swedish Academy of Sciences to scientists in the various fields of chemistry. It is one of the five Nobel Prizes established by the will of Alfred Nobel in 1895, awarded for outstanding contributions in chemistry, physics, literature,...
was awarded to Richard F. Heck
Richard F. Heck
Richard Fred Heck is an American chemist noted for the discovery and development of the Heck reaction, which uses palladium to catalyze organic chemical reactions that couple aryl halides with alkenes....
, Ei-ichi Negishi
Ei-ichi Negishi
is a Japanese chemist who has spent most of his career at Purdue University, United States. He is best known for his discovery of the Negishi coupling. He was awarded the 2010 Nobel Prize in Chemistry "for palladium catalyzed cross couplings in organic synthesis" jointly with Richard F. Heck and...
and Akira Suzuki
Akira Suzuki (chemist)
is a Japanese chemist and Nobel Prize Laureate , who first published the Suzuki reaction, the organic reaction of an aryl- or vinyl-boronic acid with an aryl- or vinyl-halide catalyzed by a palladium complex, in 1979.-Life:...
for their work on palladium-catalyzed cross couplings in organic synthesis.