Coupling reaction

In organic chemistry, a coupling reaction is a type of reaction in which two reactant molecules are bonded together. Such reactions often require the aid of a metal catalyst. In one important reaction type, a main group organometallic compound of the type R-M (where R = organic group, M = main group centre metal atom) 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.Organic Synthesis using Transition Metals Rod Bates New Trends in Cross-Coupling: Theory and Applications Thomas Colacot (Editor) 2014

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: Homocouplings joining two identical partners. The product is symmetrical Heterocouplings joining two different partners. These reactions are also called cross-coupling reactions. The product is unsymmetrical, .

Homo-coupling types Coupling reactions are illustrated by the Ullmann reaction:

ReactionYearOrganic compoundCouplerRemarkWurtz reaction1855R-Xsp3Na as reductantdry ether as mediumPinacol coupling reaction1859R-HC=O or R2(C=O) various metalsrequires proton donorGlaser coupling1869RC≡CHspCuO2 as H-acceptorUllmann reaction1901Ar-Xsp2Cuhigh temperaturesFittig reaction Ar-Xsp2Nadry ether as mediumScholl reaction1910ArHsp2NaAlCl4(l)O2 as H-acceptor; presumably trace Fe3+ catalyst; requires high heat

Cross-coupling types

ReactionYearReactant AReactant BCatalystRemarkGrignard reaction1900R-MgBrsp, sp2, sp3R-HC=O or R(C=O)R2sp2not catalyticGomberg–Bachmann reaction1924Ar-Hsp2Ar'-N2+X−sp2not catalyticCadiot–Chodkiewicz coupling1957RC≡CHspRC≡CXspCurequires baseCastro–Stephens coupling1963RC≡CHspAr-X sp2Curequires baseCorey–House synthesis1967R2CuLi or RMgX sp3R-Xsp2, sp3 CuCu-catalyzed version by Kochi, 1971Cassar reaction1970Alkenesp2R-X sp3Pdrequires baseKumada coupling1972Ar-MgBrsp2, sp3Ar-X sp2Pd or Ni or FeHeck reaction1972alkenesp2Ar-X sp2Pd or Nirequires baseSonogashira coupling1975RC≡CHspR-X sp3 sp2Pd and Curequires baseMurahashi coupling1975RLisp2, sp3Ar-Xsp2Pd or NiPd-catalyzed version by Murahashi, 1979Negishi coupling1977R-Zn-Xsp3, sp2, spR-X sp3 sp2Pd or NiStille reaction1978R-SnR3sp3, sp2, spR-X sp3 sp2PdSuzuki reaction1979R-B(OR)2sp2R-X sp3 sp2Pd or Nirequires baseHiyama coupling1988R-SiR3sp2R-X sp3 sp2Pdrequires baseBuchwald–Hartwig amination1994R2N-H sp3R-Xsp2Pd N-C coupling,second generation free amineFukuyama coupling1998R-Zn-Isp3RCO(SEt)sp2Pd or NiLiebeskind–Srogl coupling2000R-B(OR)2sp3, sp2RCO(SEt) Ar-SMesp2Pd requires CuTC(Li) Cross dehydrogenative coupling(CDC)2004R-Hsp, sp2, sp3R'-H sp, sp2, sp3Cu, Fe, Pd etcrequires oxidant or dehydrogenationWurtz–Fittig reaction1864R-Xsp3Ar-Xsp2Nadry ether

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

References