Coupling reaction

A coupling reaction in organic chemistry is a general term for a variety of reactions where two fragments are joined together with the aid of a metal catalyst. In one important reaction type, a main group organometallic compound of the type R-M (R = organic fragment, M = main group center) reacts with an organic halide of the type R'-X with formation of a new carbon-carbon bond in the product R-R'. The most common type of coupling reaction is the cross coupling reaction.

Richard F. Heck, Ei-ichi Negishi, and Akira Suzuki were awarded the 2010 Nobel Prize in Chemistry for developing palladium-catalyzed cross coupling reactions.

Broadly speaking, two types of coupling reactions are recognized:

Homo-coupling types

Coupling reactions are illustrated by the famous Ullmann reaction:

Ullmann overview
Reaction Year Reactant A Reactant B Reagent Remark
Wurtz reaction 1855 R-X sp3 R-X sp3 Na as reducing agent
Pinacol coupling reaction 1859 R-HC=O or R2(C=O) R-HC=O or R2(C=O) various metals requires proton donor
Glaser coupling 1869 RC≡CH sp RC≡CH sp Cu O2 as H-acceptor
Ullmann reaction 1901 Ar-X sp2 Ar-X sp2 Cu high temperatures

Cross-coupling types

An illustrative cross-coupling reaction is the Heck coupling of an alkene and an aryl halide:

The Heck reaction
Reaction Year Reactant A Reactant B Catalyst Remark
Grignard reaction 1900 R-MgBr sp, sp2, sp3 R-HC=O or R(C=O)R2 sp2 not catalytic
Gomberg-Bachmann reaction 1924 Ar-H sp2 Ar'-N2+X sp2 not catalytic
Cadiot-Chodkiewicz coupling 1957 RC≡CH sp RC≡CX sp Cu requires base
Castro-Stephens coupling 1963 RC≡CH sp Ar-X sp2 Cu
Corey-House synthesis 1967 R2CuLi or RMgX sp3 R-X sp2, sp3 Cu Cu-catalyzed version by Kochi, 1971
Cassar reaction 1970 Alkene sp2 R-X sp3 Pd requires base
Kumada coupling 1972 Ar-MgBr sp2, sp3 Ar-X sp2 Pd or Ni or Fe
Heck reaction 1972 alkene sp2 Ar-X sp2 Pd or Ni requires base
Sonogashira coupling 1975 RC≡CH sp R-X sp3 sp2 Pd and Cu requires base
Murahashi coupling 1975 RLi sp2, sp3 Ar-X sp2 Pd or Ni Pd-catalyzed version by Murahashi, 1979
Negishi coupling 1977 R-Zn-X sp3, sp2, sp R-X sp3 sp2 Pd or Ni
Stille cross coupling 1978 R-SnR3 sp3, sp2, sp R-X sp3 sp2 Pd
Suzuki reaction 1979 R-B(OR)2 sp2 R-X sp3 sp2 Pd or Ni requires base
Hiyama coupling 1988 R-SiR3 sp2 R-X sp3 sp2 Pd requires base
Buchwald-Hartwig reaction 1994 R2N-H sp3 R-X sp2 Pd N-C coupling,
second generation free amine
Fukuyama coupling 1998 R-Zn-I sp3 RCO(SEt) sp2 Pd or Ni
Liebeskind–Srogl coupling 2000 R-B(OR)2 sp3, sp2 RCO(SEt) Ar-SMe sp2 Pd requires CuTC
(Li) Cross dehydrogenative coupling(CDC) 2004 R-H sp, sp2, sp3 R'-H sp, sp2, sp3 Cu, Fe, Pd etc requires oxidant or dehydrogenation

Applications

Coupling reactions are routinely employed in the preparation of pharmaceuticals. Conjugated polymers are prepared using this technology as well.


This page was last updated at 2022-04-18 05:43 UTC. Update now. View original page.

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