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Coupling reaction - Wikipedia, the free encyclopedia

Coupling reaction
From Wikipedia, the free encyclopedia

A coupling reaction in organic chemistry is a catch-all term for a variety of reactions where two hydrocarbon fragments are coupled with the aid of a metal catalyst. In one important reaction type a main group organometallic compound of the type RM (R = organic fragment, M = main group centre) reacts with an organic halide of the type R'X with formation of a new carbon-carbon bond in the product R-R' [1] Contributions to coupling reactions by Eiichi Negishi and Akira Suzuki were recognized with the 2010 Nobel Prize in Chemistry, which was shared with Richard F. Heck.[2] Broadly speaking, two types of coupling reactions are recognized: cross couplings involve reactions between two different partners, for example bromobenzene (PhBr) and vinyl chloride to give styrene (PhCH=CH2). homocouplings couple two identical partners, for example, the conversion of iodobenzene (PhI) to biphenyl (Ph-Ph).

Contents
1 Mechanism 1.1 Catalysts 1.2 Leaving groups 1.3 Operating conditions 2 Coupling types 3 Miscellaneous reactions 4 Applications 5 References

Mechanism
The reaction mechanism usually begins with oxidative addition of one organic halide to the catalyst. Subsequently, the second partner undergoes transmetallation, which places both coupling partners on the same metal centre. The final step is reductive elimination of the two coupling fragments to regenerate the catalyst and give the organic product. Unsaturated organic groups couple more easily in part because they add readily. The intermediates are also less prone to beta-hydride elimination.[3] In one computational study, unsaturated organic groups were shown to undergo much easier coupling reaction on the metal center.[4] The rates for reductive elimination followed the following order: vinyl-vinyl > phenyl-phenyl > alkynyl-alkynyl > alkyl-alkyl. The activation barriers and the reaction energies for unsymmetrical R-R couplings were found to be close to the averages of the corresponding values of the symmetrical R-R and R-R coupling reactions; for example: vinyl-vinyl > vinyl-alkyl > alkyl-alkyl. Another mechanistic approach proposes that specifically in aqueous solutions, coupling actually occurs via a radical mechanism rather than a metal-assisted one.[5]
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Coupling reaction - Wikipedia, the free encyclopedia

Catalysts
The most popular metal catalyst is palladium, but some processes often use nickel and copper. A common catalyst is tetrakis(triphenylphosphine)palladium(0). Palladium catalysed reactions have several advantages including functional group tolerance, low sensitivity of organopalladium compounds towards water and air. Reviews have been written for example on cobalt,[6] palladium [7][8][9][10][11] and nickel [12] mediated reactions and on applications [13][14]

Leaving groups
The leaving group X in the organic partner is usually bromide, iodide or triflate. Ideal leaving groups are chloride, since organic chlorides are cheaper than related compounds. The main group metal in the organometallic partner usually is tin, zinc, or boron.

Operating conditions
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. Another example of coupling in aqueous media, with the main reacting agent being trimolybdenum-alkylidyne clusters, is that of Bogoslavsky et al.[15] In general, the oxygen in the air is more able to disrupt coupling reactions, because many of these reactions occur via unsaturated metal complexes that 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 toward oxygen. Some catalysts might be easily poisoned by heterocycles under prolonged reaction at elavated temperature. To avoid this, chemists often use pressure reactors to accelerate reactions at high temperature and pressure. Q-Tube (http://www.qlabtech.com) and microwave synthesizer are available safe pressure reactors.

Coupling types
Coupling reactions include (not exhaustive): Reaction Wurtz reaction Glaser coupling Ullmann reaction GombergBachmann reaction year Reactant A 1855 R-X sp Reactant B R-X RCCH Ar-X homo/cross catalyst remark Na Cu Cu O2 as Hacceptor high temperatures requires base
2/5

sp homo sp homo sp homo

1869 RCCH sp 1901 Ar-X sp

1924 Ar-H

sp

Ar-N2X

sp homo

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Coupling reaction - Wikipedia, the free encyclopedia

CadiotChodkiewicz coupling Castro-Stephens coupling Gilman reagent coupling Cassar reaction

1957 RCCH sp 1963 RCCH sp 1967 R2CuLi 1970 Alkene sp ArMgBr sp, sp sp

RCCX Ar-X R-X R-X Ar-X R-X R-X R-X

sp cross sp cross cross sp cross sp cross sp cross sp cross sp sp cross sp sp cross sp sp cross sp sp cross sp sp cross

Cu Cu

requires base

Pd Pd or Ni Pd Pd and Cu Pd or Ni Pd Pd Pd

requires base

Kumada coupling 1972 Heck reaction Sonogashira coupling Negishi coupling Stille cross coupling Suzuki reaction Hiyama coupling BuchwaldHartwig reaction Fukuyama coupling

1972 alkene

requires base requires base

1975 RCCH sp sp, 1977 R-Zn-X sp, sp sp, 1978 R-SnR3 sp, sp 1979 Rsp B(OR)2

R-X R-X R-X

requires base requires base N-C coupling, second generation free amine

1988 R-SiR3 sp R N-R 1994 2 sp SnR3 1998 R-Zn-I sp3

R-X

Pd

RCO(SEt) sp2 cross RCO(SEt) sp2 cross

Pd Pd requires CuTC

RLiebeskindSrogl sp3, 2000 B(OR)2 sp2 coupling

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.[16]
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Coupling reaction - Wikipedia, the free encyclopedia

One method for palladium-catalyzed cross-coupling reactions of aryl halides with fluorinated arenes was reported by Keith Fagnou and co-workers. It is unusual in that it involves C-H functionalisation at an electron deficient arene.[17]

Applications
Many coupling reactions have found their way into pharmaceutical industry [18] and into conjugated organic materials [19]

References
1. ^ Organic Synthesis using Transition Metals Rod Bates ISBN 978-1-84127-107-1 2. ^ "The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki" (http://nobelprize.org/nobel_prizes/chemistry/laureates/2010/). NobelPrize.org. 2010-10-06. Retrieved 2010-10-06. 3. ^ Hartwig, J. F. Organotransition Metal Chemistry, from Bonding to Catalysis; University Science Books: New York, 2010. ISBN 1-891389-53-X 4. ^ V. P. Ananikov, D. G. Musaev, K. Morokuma, Theoretical Insight into the C-C Coupling Reactions of the Vinyl, Phenyl, Ethynyl, and Methyl Complexes of Palladium and Platinum Organometallics 2005, 24, 715. doi:10.1021/om0490841 (http://dx.doi.org/10.1021%2Fom0490841) 5. ^ Benny Bogoslavsky, Ophir Levy, Anna Kotlyar, Miri Salem, Faina Gelman and Avi Bino (2012). "Do Carbyne Radicals Really Exist in Aqueous Solution?". Angewandte Chemie International Edition 51 (1): 9094. doi:10.1002/anie.201103652 (http://dx.doi.org/10.1002%2Fanie.201103652). PMID 22031005 (//www.ncbi.nlm.nih.gov/pubmed/22031005). 6. ^ Cobalt-Catalyzed Cross-Coupling Reactions Grard Cahiez and Alban Moyeux Chem. Rev., 2010, 110 (3), pp 14351462 Publication Date (Web): February 11, 2010 (Review) doi:10.1021/cr9000786 (http://dx.doi.org/10.1021%2Fcr9000786) 7. ^ CarbonCarbon Coupling Reactions Catalyzed by Heterogeneous Palladium Catalysts Lunxiang Yin and Jrgen Liebscher Chem. Rev., 2007, 107 (1), pp 133173 Publication Date (Web): December 21, 2006 (Article) doi:10.1021/cr0505674 (http://dx.doi.org/10.1021%2Fcr0505674) 8. ^ Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners Ranjan Jana, Tejas P. Pathak, and Matthew S. Sigman Chem. Rev., 2011, 111 (3), pp 1417 1492 doi: 10.1021/cr100327p (http://dx.doi.org/10.1021%2Fcr100327p) 9. ^ Efficient, Selective, and Recyclable Palladium Catalysts in CarbonCarbon Coupling Reactions rpd Molnr Chem. Rev., 2011, 111 (3), pp 22512320 doi:10.1021/cr100355b (http://dx.doi.org/10.1021%2Fcr100355b) 10. ^ Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds Norio. Miyaura, Akira. Suzuki Chem. Rev., 1995, 95 (7), pp 24572483 doi:10.1021/cr00039a007 (http://dx.doi.org/10.1021%2Fcr00039a007) 11. ^ Diazonium Salts as Substrates in Palladium-Catalyzed Cross-Coupling Reactions Anna Roglans, Anna PlaQuintana, and Marcial Moreno-Maas Chem. Rev., 2006, 106 (11), pp 46224643 doi:10.1021/cr0509861 (http://dx.doi.org/10.1021%2Fcr0509861) 12. ^ Nickel-Catalyzed Cross-Couplings Involving CarbonOxygen Bonds Brad M. Rosen, Kyle W. Quasdorf, Daniella A. Wilson, Na Zhang, Ana-Maria Resmerita, Neil K. Garg, and Virgil Percec Chem. Rev., 2011, 111 (3), pp 1346
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13. 14.

15.

16.

17.

18. 19.

1416 doi:10.1021/cr100259t (http://dx.doi.org/10.1021%2Fcr100259t) ^ Selected Patented Cross-Coupling Reaction Technologies Jean-Pierre Corbet and Grard Mignani Chem. Rev., 2006, 106 (7), pp 26512710 2006 (Article) doi:10.1021/cr0505268 (http://dx.doi.org/10.1021%2Fcr0505268) ^ Copper-Mediated Coupling Reactions and Their Applications in Natural Products and Designed Biomolecules Synthesis Gwilherm Evano, Nicolas Blanchard and Mathieu Toumi Chem. Rev., 2008, 108 (8), pp 30543131 doi:10.1021/cr8002505 (http://dx.doi.org/10.1021%2Fcr8002505) ^ Benny Bogoslavsky, Ophir Levy, Anna Kotlyar, Miri Salem, Faina Gelman and Avi Bino (2012). "Do Carbyne Radicals Really Exist in Aqueous Solution?". Angewandte Chemie International Edition 51 (1): 9094. doi:10.1002/anie.201103652 (http://dx.doi.org/10.1002%2Fanie.201103652). PMID 22031005 (//www.ncbi.nlm.nih.gov/pubmed/22031005). ^ A. Bino, M. Ardon and E. Shirman (2005). "Formation of a Carbon-Carbon Triple Bond by Coupling Reactions In Aqueous Solution". Science 308 (5719): 234235. Bibcode:2005Sci...308..234B (http://adsabs.harvard.edu/abs/2005Sci...308..234B). doi:10.1126/science.1109965 (http://dx.doi.org/10.1126%2Fscience.1109965). PMID 15821086 (//www.ncbi.nlm.nih.gov/pubmed/15821086). ^ M. Lafrance, C. N. Rowley, T. K. Woo and K. Fagnou (2006). "Catalytic Intermolecular Direct Arylation of Perfluorobenzenes". J. Am. Chem. Soc. 128 (27): 87548756. doi:10.1021/ja062509l (http://dx.doi.org/10.1021%2Fja062509l). PMID 16819868 (//www.ncbi.nlm.nih.gov/pubmed/16819868). ^ R.H. Crabtree, The Organometallic Chemistry of the Transition Metals 4th Ed. ^ Organotransition Metal Chemistry: From Bonding to Catalysis John Hartwig

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