Coupling reaction

{{Short description|Type of reaction in organic chemistry}}

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.<ref>''Organic Synthesis using Transition Metals'' Rod Bates {{ISBN|978-1-84127-107-1}}</ref><ref>''New Trends in Cross-Coupling: Theory and Applications'' Thomas Colacot (Editor) 2014 {{ISBN|978-1-84973-896-5}}</ref><ref name=Pharma>{{cite book|author=King, A. O.|author2=Yasuda, N.|title=Organometallics in Process Chemistry|pages=205–245 |chapter=Palladium-Catalyzed Cross-Coupling Reactions in the Synthesis of Pharmaceuticals|series=Topics in Organometallic Chemistry |year=2004 |volume=6 |doi=10.1007/b94551|publisher = Springer|location=Heidelberg|isbn=978-3-540-01603-8 }}</ref>

Richard F. Heck, Ei-ichi Negishi, and Akira Suzuki were awarded the 2010 Nobel Prize in Chemistry for developing palladium-catalyzed cross coupling reactions.<ref>{{cite web|url=http://nobelprize.org/nobel_prizes/pornhemistry/laureates/2010/ |title=The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki |publisher=NobelPrize.org |date=2010-10-06 |access-date=2010-10-06}}</ref><ref>{{cite journal | doi = 10.1002/anie.201107017| pmid = 22573393| title = Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize| journal = Angewandte Chemie International Edition| volume = 51| issue = 21| pages = 5062–5085| year = 2012| last1 = Johansson Seechurn| first1 = Carin C. C.| last2 = Kitching| first2 = Matthew O.| last3 = Colacot| first3 = Thomas J.| last4 = Snieckus| first4 = Victor| url = https://durham-repository.worktribe.com/output/1323930}}</ref>

Broadly speaking, two types of coupling reactions are recognized: * Homocouplings joining two identical partners. The product is symmetrical {{chem2|R\sR}} * Heterocouplings joining two different partners. These reactions are also called cross-coupling reactions.<ref>{{March6th|page=449}}</ref> The product is unsymmetrical, {{chem2|R\sR'}}.

== Homo-coupling types == Coupling reactions are illustrated by the Ullmann reaction: class=skin-invert-image|center|350px|Ullmann overview

{|align="center" class="wikitable" !Reaction||Year ! colspan="2" align=left |Organic compound||Coupler||Remark |- |Wurtz reaction||1855||R-X||sp³||Na as reductant||dry ether as medium |- |Pinacol coupling reaction||1859||R-HC=O or R₂(C=O)|| ||various metals||requires proton donor |- |Glaser coupling||1869||RC≡CH||sp||Cu||O₂ as H-acceptor |- |Ullmann reaction||1901||Ar-X||sp²||Cu||high temperatures |- |Fittig reaction|| ||Ar-X||sp²||Na||dry ether as medium |- |Scholl reaction||1910||ArH||sp²||NaAlCl₄(''l'')||O₂ as H-acceptor; presumably trace Fe³⁺ catalyst; requires high heat |}

== Cross-coupling types == {{main|Cross-coupling reaction}}

class=skin-invert-image|center|300px|The Heck reaction

{|align="center" class="wikitable" !Reaction||Year ! colspan="2" align=left |Reactant A ! colspan="2" align=left |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||requires base |- |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<ref>{{Cite journal|last1=Hazra|first1=Susanta|last2=Johansson Seechurn|first2=Carin C. C.|last3=Handa|first3=Sachin|last4=Colacot|first4=Thomas J.|date=2021-10-15|title=The Resurrection of Murahashi Coupling after Four Decades|url=https://pubs.acs.org/doi/pdf/10.1021/acscatal.1c03564|journal=ACS Catalysis|volume=11|issue=21|pages=13188–13202|doi=10.1021/acscatal.1c03564|s2cid=244613990 |issn=2155-5435|url-access=subscription}}</ref> |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 reaction||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 amination||1994||R₂N-H ||sp³||R-X||sp²||Pd|| N-C coupling,<br />second generation free amine |- |Fukuyama coupling||1998||R-Zn-I||sp³||RCO(SEt)||sp²||Pd or Ni<ref>{{cite journal |title=Directed Nickel-Catalyzed Negishi Cross Coupling of Alkyl Aziridines |last1=Nielsen |first1=Daniel K. |last2=Huang |first2=Chung-Yang (Dennis) |last3=Doyle |first3=Abigail G. |date=2013-08-20 |journal=Journal of the American Chemical Society |volume=135 |issue=36 |pages=13605–13609 |doi=10.1021/ja4076716 |pmid= 23961769|bibcode=2013JAChS.13513605N |issn=0002-7863}}</ref>|| |- |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 |- |Wurtz–Fittig reaction |1864 |R-X |sp³ |Ar-X |sp² |Na |dry ether |}

==Applications== Coupling reactions are routinely employed in the preparation of pharmaceuticals.<ref name=Pharma/> Conjugated polymers are prepared using this technology as well.<ref name=JFH>{{cite book|author=Hartwig, J. F.|title=Organotransition Metal Chemistry, from Bonding to Catalysis |publisher=University Science Books|location=New York|year=2010|isbn=978-1-891389-53-5}}</ref>

==References== {{Reflist|2}}

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{{DEFAULTSORT:Coupling Reaction}} Category:Coupling reactions Category:Organometallic chemistry Category:Carbon-carbon bond forming reactions Category:Catalysis