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 are cross coupling reaction.[1][2][3]

Richard F. Heck, Ei-ichi Negishi, and Akira Suzuki were awarded the 2010 Nobel Prize in Chemistry for developing palladium-catalyzed cross coupling reactions.[4][5]

Broadly speaking, two types of coupling reactions are recognized:

Homo-coupling types

Coupling reactions are illustrated by the famous Ullmann reaction:

ReactionYear Reactant A Reactant BReagentRemark
Wurtz reaction1855R-Xsp3R-Xsp3Na as reducing agent
Pinacol coupling reaction1859R-HC=O or R(C=O)R2R-HC=O or R(C=O)R2various metalsrequires proton donor
Glaser coupling1869RC≡CHspRC≡CHspCuO2 as H-acceptor
Ullmann reaction1901Ar-Xsp2Ar-Xsp2Cuhigh temperatures

Cross-coupling types

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

ReactionYear Reactant A Reactant BCatalystRemark
Grignard reaction1900R-MgBrsp, sp2, sp3 R-HC=O or R(C=O)R2sp2not catalytic
Gomberg-Bachmann reaction 1924 Ar-H sp2 Ar'-N2+X- sp2 not catalytic
Cadiot-Chodkiewicz coupling1957RC≡CHspRC≡CXspCurequires base
Castro-Stephens coupling1963RC≡CHspAr-Xsp2Cu
Corey-House synthesis1967R2CuLi or RMgXsp3 R-Xsp2, sp3 Cu Cu-catalyzed version by Kochi, 1971
Cassar reaction1970Alkenesp2R-Xsp3Pdrequires base
Kumada coupling1972Ar-MgBrsp2, sp3Ar-Xsp2Pd or Ni or Fe
Heck reaction1972alkenesp2Ar-Xsp2Pd or Nirequires base
Sonogashira coupling1975RC≡CHspR-Xsp3 sp2Pd and Curequires base
Negishi coupling1977R-Zn-Xsp3, sp2, spR-Xsp3 sp2Pd or Ni
Stille cross coupling1978R-SnR3sp3, sp2, spR-Xsp3 sp2Pd
Suzuki reaction1979R-B(OR)2sp2R-Xsp3 sp2Pd or Nirequires base
Hiyama coupling1988R-SiR3sp2R-Xsp3 sp2Pdrequires base
Buchwald-Hartwig reaction1994R2N-Hsp3R-Xsp2PdN-C coupling,
second generation free amine
Fukuyama coupling1998R-Zn-Isp3RCO(SEt)sp2Pd or Ni[6]
Liebeskind–Srogl coupling2000R-B(OR)2sp3, sp2RCO(SEt) Ar-SMesp2Pdrequires CuTC

Applications

Coupling reactions are routinely employed in the preparation of pharmaceuticals.[3] Conjugated polymers are prepared using this technology as well.[7]

References

  1. Organic Synthesis using Transition Metals Rod Bates ISBN 978-1-84127-107-1
  2. New Trends in Cross-Coupling: Theory and Applications Thomas Colacot (Editor) 2014 ISBN 978-1-84973-896-5
  3. King, A. O.; Yasuda, N. "Palladium-Catalyzed Cross-Coupling Reactions in the Synthesis of Pharmaceuticals". Organometallics in Process Chemistry. Heidelberg: Springer. p. 205-245. doi:10.1007/b94551.CS1 maint: multiple names: authors list (link)
  4. "The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki". NobelPrize.org. 2010-10-06. Retrieved 2010-10-06.
  5. Johansson Seechurn, Carin C. C.; Kitching, Matthew O.; Colacot, Thomas J.; Snieckus, Victor (2012). "Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize". Angewandte Chemie International Edition. 51 (21): 5062–5085. doi:10.1002/anie.201107017. PMID 22573393.
  6. Nielsen, Daniel K.; Huang, Chung-Yang (Dennis); Doyle, Abigail G. (2013-08-20). "Directed Nickel-Catalyzed Negishi Cross Coupling of Alkyl Aziridines". Journal of the American Chemical Society. 135 (36): 13605–13609. doi:10.1021/ja4076716. ISSN 0002-7863. PMID 23961769.
  7. Hartwig, J. F. (2010). Organotransition Metal Chemistry, from Bonding to Catalysis. New York: University Science Books. ISBN 1-891389-53-X.
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.