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Coupling reaction

A coupling reaction or oxidative coupling in organic chemistry is a catch-all for a range of reactions in Organometallic chemistry where two hydrocarbon radicals are coupled with the aid of a metal containing catalyst.

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Coupling reactions should be divided into two main classes, there are the cross couplings in which two different molecules react to form one new molecule. For example the nickel chloride catalyzed reaction of an aryl magnesium halide with an aryl halide to form a biaryl.

An example of the other type of coupling (homocoupling) would be a Ullmann reaction, this is the reaction of copper metal with two molecules of an aryl halide to form a biaryl. The Ullmann reaction often requires very high temperatures, and has partly been replaced in synthetic chemistry by palladium based reactions.

Many coupling reactions involve phenols. BINOL is the C-C coupling reaction product of 2-naphthol with copper(II) chloride and 2,6-xylenol dimerises as well with iodosobenzene diacetate.

A common metal in this type of chemistry is palladium often added in the form of tetrakis(triphenylphosphine)palladium(0). This is an air sensitive compound which is very good for coupling unsaturated halogen compounds with organometallics such as tributyltin hydride.

While many coupling reactions involve reagents that are extremely susceptible to presence of water or oxygen, it is unreasonable to assume that all coupling reactions need to be performed with strict exclusion of water. It is possible to perform palladium based coupling reactions in aqueous solutions using the water soluble sulfonated phosphines made by the reaction of triphenyl phosphine with sulfuric acid. In general the oxygen in the air is more able to disrupt coupling reactions, this is because many of these reactions occur via unsaturated metal complexes which do not have 18 valence electrons. For example in nickel and palladium cross couplings a zerovalent complex with two vacant sites (or labile ligands) reacts with the carbon halogen bond to form a metal halogen and a metal carbon bond. Such a zerovalent complex with labile ligands or empty coordination sites is normally very reactive towards oxygen.

Coupling types

Coupling reactions include (not exhaustive):

Reaction	year	Reactant A		Reactant B		homo/cross	catalyst	remark
Wurtz reaction	1855			R-X	sp³	homo	Na
Glaser coupling	1869			R-X	sp	homo	Cu
Ullmann reaction	1901			R-X	sp²	homo	Cu
Gomberg-Bachmann reaction	1924			R-N₂X	sp²	homo		requires base
Cadiot-Chodkiewicz coupling	1957	alkyne	sp	R-X	sp	cross	Cu	requires base
Castro-Stephens coupling	1963	R-Cu	sp	R-X	sp²	cross
Kumada coupling	1972	R-MgBr	sp², sp³	R-X	sp²	cross	Pd or Ni
Heck reaction	1972	alkene	sp²	R-X	sp²	cross	Pd	requires base
Sonogashira coupling	1973	alkyne	sp	R-X	sp³ sp²	cross	Pd and Cu	requires base
Negishi coupling	1977	R-Zn-X	sp²	R-X	sp³ sp²	cross	Pd or Ni
Stille cross coupling	1977	R-SnR₃	sp²	R-X	sp³ sp²	cross	Pd	requires base
Suzuki reaction	1979	R-B(OR)₂	sp²	R-X	sp³ sp²	cross	Pd	requires base
Hiyama coupling	1988	R-SiR₃	sp²	R-X	sp³ sp²	cross	Pd	requires base
Buchwald-Hartwig reaction	1994	R₂N-R SnR₃	sp	R-X	sp²	cross	Pd	N-C coupling, second generation free amine
Coupling reaction overview. For references consult satellite pages

Miscellaneous reactions

In one study an unusual coupling reaction was described in which an organomolybdenum compound, [Mo₃(CCH₃)₂(OAc)₆(H₂O)₃](CF₃SO₃)₂ not only sat on a shelf for 30 years without any sign of degradation but also decomposed in water to generate 2-butyne which is the coupling adduct of its two ethylidyne ligands. This according to the researchers opens another way for aqueous organometallic chemistry.^[1]

One method for palladium-catalyzed cross coupling reactions of aryl halides with fluorinated arenes, involves DMA. It is unusual in that it involves C-H functionalisation at an electron deficient arene.^[2]

References

^ A. Bino, M. Ardon and E. Shirman (2005). "Formation of a Carbon-Carbon Triple Bond by Coupling Reactions In Aqueous Solution". Science 308 (5719): 234-235. doi:10.1126/science.1109965.
^ M. Lafrance, C. N. Rowley, T. K. Woo and K. Fagnou (2006). "Catalytic Intermolecular Direct Arylation of Perfluorobenzenes". J. Am. Chem. Soc. 128 (27): 8754-8756. doi:10.1021/ja062509l.

Categories: Organometallic chemistry | Carbon-carbon bond forming reactions

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Coupling_reaction". A list of authors is available in Wikipedia.