Coupling reaction

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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.

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-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

  1. 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.
  2. 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.
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