偶聯反應

偶聯反應，也寫作耦合反應、偶合反應或耦聯反應，是兩化學實體（或單位）結合生成一分子的有機化學反應。狹義的偶聯反應是涉及有機金屬催化劑的碳－碳鍵形成反應，根據類型的不同，又可分為交叉偶聯和自身偶聯反應。在偶聯反應中有一類重要的反應，RM（R＝有機片段；M＝主基團中心）與R'X的有機鹵素化合物反應，形成有新碳－碳鍵的產物R－R'^[1]^[2]。

根岸英一、鈴木章與理查德·赫克開發鈀催化偶聯反應，貢獻突出，共同獲授2010年度諾貝爾化學獎^[3]^[4]。

偶聯反應大體可分為兩種類型：

交叉偶聯反應：兩種不同片段連接成一分子，如溴苯（PhBr）與乙烯形成苯乙烯(PhCH=CH₂)。
自身偶聯反應：相同的兩片段形成一分子，如碘苯（PhI)自身形成聯苯（Ph－Ph)。

偶聯機理通常起始於有機鹵代烴和催化劑氧化加成；第二步是另一分子與其轉移金屬化，將待偶聯的兩分子接於同一金屬中心；最後一步是還原消除，待偶聯的兩分子結合在一起形成新分子並再生催化劑。不飽和的有機基團在加合一步速度更快，通常易於偶聯。中間體通常不傾向β-氫消除。^[5]

一項計算化學研究中表明，不飽和有機基團更易於在金屬中心偶聯。^[6]還原消除的速率高低如下：

乙烯基－乙烯基＞苯基－苯基＞炔基－炔基＞烷基－烷基

不對稱的R－R′形式偶聯反應，其活化能壘與反應能量與相應的對稱偶聯反應R－R與R′－R′的平均值相近，如：乙烯基－乙烯基＞乙烯基－烷基＞烷基－烷基。

另一種假說認為，水溶液偶聯反應其實是通過自由基機理，而不是金屬－參與機理。^[7]

催化劑

偶聯反應最常用的金屬催化劑是鈀催化劑，有時也用鎳與銅。四（三苯基膦）鈀是常用的鈀催化劑。鈀催化的有機反應有許多優點，如：官能團的耐受性強，有機鈀化合物對水和空氣甚穩定。

如下一些關於鈷催化的偶聯反應的綜述^[8]，鈀^[9]^[10]^[11]^[12]^[13]和鎳^[14]介導的反應以及它們的用途^[15]^[16]。

離去基團

離去基團在有機偶聯反應常為溴、碘或三氟甲磺酰基。有機氯化物相對這些離去基團更廉價易得，故氯是較理想的離去基團。與之反應的有機金屬化合物還有錫、鋅或硼。

操作條件

雖然大多偶聯反應涉及的試劑都對水和空氣極其敏感，但不可認為所有有機偶聯反應需要絕對的無水無氧條件。有些有機鈀介導的反應就可在水溶液中，用三苯基膦和硫酸製備的磺化膦試劑反應。^[7]總體來講，大多這類反應都藉不飽和金屬絡合物反應，而這些絡合物都不滿足18共價電子的穩定結構，故空氣中的氧氣能影響偶聯反應。

常見偶聯反應有：

反應名稱	發現年代	反應物A		反應物B		類型	催化劑	備註
武茲反應（Wurtz reaction）	1855	R－X	sp³	R－X	sp³	自身		以鈉消除反應物的鹵原子
格拉澤偶聯反應（Glaser coupling）	1869	RC≡CH	sp	RC≡CH	sp	自身	Cu	氧氣作H受體
烏爾曼反應（Ullmann reaction）	1901	Ar－X	sp²	Ar－X	sp²	自身	Cu	高溫
岡伯格－巴克曼反應	1924	Ar－H	sp²	Ar－N₂X	sp²	自身		需鹼參與
Cadiot－Chodkiewicz偶聯反應	1957	RC≡CH	sp	RC≡CX	sp	交叉	Cu	需鹼參與
Castro－Stephens偶聯反應	1963	RC≡CH	sp	Ar－X	sp²	交叉	Cu
吉爾曼試劑偶聯反應（Gilman reagent coupling）	1967	R₂CuLi		R－X		交叉
Cassar反應	1970	烯烴	sp²	R－X	sp³	交叉	Pd	需鹼參與
熊田偶聯反應（Kumada coupling）	1972	Ar－MgBr	sp²／sp³	Ar－X	sp²	交叉	Pd或Ni
赫克反應（Heck reaction）	1972	烯烴	sp²	R－X	sp²	交叉	Pd	需鹼參與
薗頭偶聯反應（Sonogashira coupling）	1975	RC≡CH	sp	R－X	sp³／sp²	交叉	Pd和Cu	需鹼參與
根岸偶聯反應（Negishi coupling）	1977	R－Zn－X	sp³／sp²／sp	R－X	sp³／sp²	交叉	Pd或Ni
施蒂勒反應（Stille coupling）	1978	R－SnR₃	sp³／sp²／sp	R－X	sp³／sp²	交叉	Pd
鈴木反應（Suzuki reaction）	1979	R－B(OR)₂	sp²	R－X	sp³／sp²	交叉	Pd	需鹼參與
Hiyama偶聯反應	1988	R－SiR₃	sp²	R－X	sp³／sp²	交叉	Pd	需鹼參與
Buchwald–Hartwig偶聯反應	1994	R₂N－R SnR₃	sp	R－X	sp²	交叉	Pd	N－C偶聯反應
福山偶聯反應（Fukuyama coupling）	1998	RCO(SEt)	sp²	R－Zn－I	sp³	交叉	Pd
偶聯反應一覽. 參考文獻見子頁面

一種基於芳基鹵代烴和全氟代苯的鈀－催化偶聯反應由基思·法紐（Keith Fagnou）和其同事所報道。對於這種缺電子的芳環來講，這類官能團化反應很不尋常。^[17]

許多偶聯反應已經廣泛的應用於製藥工業^[18]和相關的工業原料^[19]。

鈀催化偶聯反應

[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]
The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki. NobelPrize.org. 2010-10-06 [2010-10-06]. （原始內容存檔於2012-10-26）.
[4]
Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize Dr. Carin C. C. Johansson Seechurn, Dr. Matthew O. Kitching, Dr. Thomas J. Colacot, Prof. Victor Snieckus Angew. Chem. Int. Ed. 2012, 51, 5062-5085. doi:10.1002/anie.201107017
[5]
Hartwig, J. F. Organotransition Metal Chemistry, from Bonding to Catalysis; University Science Books: New York, 2010. ISBN 189138953X
[6]
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
[7]
Benny Bogoslavsky, Ophir Levy, Anna Kotlyar, Miri Salem, Faina Gelman and Avi Bino. Do Carbyne Radicals Really Exist in Aqueous Solution?. Angewandte Chemie International Edition. 2012, 51 (1): 90–94. PMID 22031005. doi:10.1002/anie.201103652.
[8]
Cobalt-Catalyzed Cross-Coupling Reactions Grard Cahiez and Alban Moyeux Chem. Rev., 2010, 110 (3), pp 1435–1462 Publication Date (Web): February 11, 2010 (Review) doi:10.1021/cr9000786
[9]
Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous Palladium Catalysts Lunxiang Yin and Jürgen Liebscher Chem. Rev., 2007, 107 (1), pp 133–173 Publication Date (Web): December 21, 2006 (Article) doi:10.1021/cr0505674
[10]
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
[11]
Efficient, Selective, and Recyclable Palladium Catalysts in Carbon−Carbon Coupling Reactions rpd Molnr Chem. Rev., 2011, 111 (3), pp 2251–2320 doi:10.1021/cr100355b
[12]
Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds Norio. Miyaura, Akira. Suzuki Chem. Rev., 1995, 95 (7), pp 2457–2483 doi:10.1021/cr00039a007
[13]
Diazonium Salts as Substrates in Palladium-Catalyzed Cross-Coupling Reactions Anna Roglans, Anna Pla-Quintana, and Marcial Moreno-Mañas Chem. Rev., 2006, 106 (11), pp 4622–4643 doi:10.1021/cr0509861
[14]
Nickel-Catalyzed Cross-Couplings Involving Carbon−Oxygen 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 1346–1416 doi:10.1021/cr100259t
[15]
Selected Patented Cross-Coupling Reaction Technologies Jean-Pierre Corbet and Gérard Mignani Chem. Rev., 2006, 106 (7), pp 2651–2710 2006 (Article) doi:10.1021/cr0505268
[16]
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 3054–3131 doi:10.1021/cr8002505
[17]
M. Lafrance, C. N. Rowley, T. K. Woo and K. Fagnou. Catalytic Intermolecular Direct Arylation of Perfluorobenzenes. J. Am. Chem. Soc. 2006, 128 (27): 8754–8756. PMID 16819868. doi:10.1021/ja062509l.
[18]
R.H. Crabtree, The Organometallic Chemistry of the Transition Metals 4th Ed.
[19]
Organotransition Metal Chemistry: From Bonding to Catalysis John Hartwig

[1] [1]
Organic Synthesis using Transition Metals Rod Bates ISBN 978-1-84127-107-1

[2] [2]
New Trends in Cross-Coupling: Theory and Applications Thomas Colacot (Editor) 2014 ISBN 978-1-84973-896-5

[3] [3]
The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki. NobelPrize.org. 2010-10-06 [2010-10-06]. （原始內容存檔於2012-10-26）.

[4] [4]
Palladium-Catalyzed Cross-Coupling: A Historical Contextual Perspective to the 2010 Nobel Prize Dr. Carin C. C. Johansson Seechurn, Dr. Matthew O. Kitching, Dr. Thomas J. Colacot, Prof. Victor Snieckus Angew. Chem. Int. Ed. 2012, 51, 5062-5085. doi:10.1002/anie.201107017

[5] [5]
Hartwig, J. F. Organotransition Metal Chemistry, from Bonding to Catalysis; University Science Books: New York, 2010. ISBN 189138953X

[6] [6]
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

[#1-7] [7]
Benny Bogoslavsky, Ophir Levy, Anna Kotlyar, Miri Salem, Faina Gelman and Avi Bino. Do Carbyne Radicals Really Exist in Aqueous Solution?. Angewandte Chemie International Edition. 2012, 51 (1): 90–94. PMID 22031005. doi:10.1002/anie.201103652.

[8] [8]
Cobalt-Catalyzed Cross-Coupling Reactions Grard Cahiez and Alban Moyeux Chem. Rev., 2010, 110 (3), pp 1435–1462 Publication Date (Web): February 11, 2010 (Review) doi:10.1021/cr9000786

[9] [9]
Carbon−Carbon Coupling Reactions Catalyzed by Heterogeneous Palladium Catalysts Lunxiang Yin and Jürgen Liebscher Chem. Rev., 2007, 107 (1), pp 133–173 Publication Date (Web): December 21, 2006 (Article) doi:10.1021/cr0505674

[10] [10]
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

[11] [11]
Efficient, Selective, and Recyclable Palladium Catalysts in Carbon−Carbon Coupling Reactions rpd Molnr Chem. Rev., 2011, 111 (3), pp 2251–2320 doi:10.1021/cr100355b

[12] [12]
Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds Norio. Miyaura, Akira. Suzuki Chem. Rev., 1995, 95 (7), pp 2457–2483 doi:10.1021/cr00039a007

[13] [13]
Diazonium Salts as Substrates in Palladium-Catalyzed Cross-Coupling Reactions Anna Roglans, Anna Pla-Quintana, and Marcial Moreno-Mañas Chem. Rev., 2006, 106 (11), pp 4622–4643 doi:10.1021/cr0509861

[14] [14]
Nickel-Catalyzed Cross-Couplings Involving Carbon−Oxygen 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 1346–1416 doi:10.1021/cr100259t

[15] [15]
Selected Patented Cross-Coupling Reaction Technologies Jean-Pierre Corbet and Gérard Mignani Chem. Rev., 2006, 106 (7), pp 2651–2710 2006 (Article) doi:10.1021/cr0505268

[16] [16]
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 3054–3131 doi:10.1021/cr8002505

[17] [17]
M. Lafrance, C. N. Rowley, T. K. Woo and K. Fagnou. Catalytic Intermolecular Direct Arylation of Perfluorobenzenes. J. Am. Chem. Soc. 2006, 128 (27): 8754–8756. PMID 16819868. doi:10.1021/ja062509l.

[18] [18]
R.H. Crabtree, The Organometallic Chemistry of the Transition Metals 4th Ed.

[19] [19]
Organotransition Metal Chemistry: From Bonding to Catalysis John Hartwig

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

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[15]

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[17]

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[19]

偶聯反應

催化劑

離去基團

操作條件

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偶聯反應

催化劑

離去基團

操作條件

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機理

類型

雜項反應

應用

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參考資料