偶联反はん应

偶联反はん应，也写作さく耦合反應はんのう、偶合反はん应或ある耦联反はん应，是ぜ两化学がく实体（或ある单位）结合生成せいせい一いち分子ぶんし的てき有ゆう机つくえ化学かがく反はん应。狭せま义的偶联反はん应是涉わたる及有ゆう机つくえ金属きんぞく催化剂的てき碳－碳键形成けいせい反はん应，根ね据すえ类型的てき不同ふどう，又また可分かぶん为交叉こうさ偶联和わ自身じしん偶联反はん应。在ざい偶联反はん应中有ちゅうう一类重要的反应，RM（R＝有ゆう机つくえ片へん段だん；M＝主しゅ基もと团中心ちゅうしん）与あずかR'X的てき有ゆう机つくえ卤素化合かごう物ぶつ反はん应，形成けいせい有ゆう新しん碳－碳键的てき产物R－R'^[1]^[2]。

根岸ねぎし英一ひでかず、铃木章あきら与あずか理り查德·赫克开发钯催化か偶联反はん应，贡献突出とっしゅつ，共同きょうどう獲え授2010年度ねんど诺贝尔化学がく奖^[3]^[4]。

偶联反はん应大体だいたい可分かぶん为两种类型がた：

交叉こうさ偶联反はん应：两种不同ふどう片へん段だん连接成なり一いち分子ぶんし，如溴苯（PhBr）与あずか乙おつ烯形成けいせい苯乙烯(PhCH=CH₂)。
自身じしん偶联反はん应：相あい同どう的てき两片段だん形成けいせい一いち分子ぶんし，如碘苯（PhI)自身じしん形成けいせい联苯（Ph－Ph)。

机つくえ理り

偶联机つくえ理り通常つうじょう起おこり始はじめ于有机つくえ卤代烃和催化剂氧化加か成なり；第だい二步是另一分子与其转移金属きんぞく化か，将はた待まち偶联的てき两分子ぶんし接せっ于同一いち金属きんぞく中心ちゅうしん；最さい后きさき一いち步ほ是ぜ还原消しょう除じょ，待まち偶联的てき两分子ぶんし结合在ざい一起形成新分子并再生催化剂。不ふ饱和的てき有ゆう机つくえ基もと团在加か合あい一いち步ほ速度そくど更さら快かい，通常つうじょう易えき于偶联。中ちゅう间体通常つうじょう不ふ倾向βべーた-氢消除じょ。^[5]

一项计算化学研究中表明，不ふ饱和有ゆう机つくえ基もと团更易えき于在金属きんぞく中心ちゅうしん偶联。^[6]还原消しょう除じょ的てき速そく率りつ高低こうてい如下：

乙おつ烯基－乙おつ烯基＞苯基－苯基＞炔基－炔基＞烷基－烷基

不ふ对称的てきR－R′形式けいしき偶联反はん应，其活化か能のう垒与反はん应能量りょう与あずか相あい应的对称偶联反はん应R－R与あずかR′－R′的てき平均へいきん值相近すけちか，如：乙おつ烯基－乙おつ烯基＞乙おつ烯基－烷基＞烷基－烷基。

另一种假说认为，水溶液すいようえき偶联反はん应其实是通どおり过自由じゆう基もと机つくえ理り，而不是ぜ金属きんぞく－参与さんよ机つくえ理り。^[7]

催化剂

偶联反はん应最常用じょうよう的てき金属きんぞく催化剂是钯催化剂，有ゆう时也用よう镍与あずか铜。四よん（三さん苯基膦）钯是ぜ常用じょうよう的てき钯催化か剂。钯催化か的てき有ゆう机つくえ反はん应有许多优点，如：官能かんのう团的てき耐たい受性强きょう，有ゆう机つくえ钯化合かごう物ぶつ对水みず和わ空そら气甚穩定じょう。

如下一些关于钴催化的偶联反应的综述^[8]，钯^[9]^[10]^[11]^[12]^[13]和かず镍^[14]介かい导的反はん应以及它们的用途ようと^[15]^[16]。

离去基もと团

离去基もと团在ざい有ゆう机つくえ偶联反はん应常为溴、碘或ある三氟甲磺酰基。有ゆう机つくえ氯化物相もっそう对这些离去基もと团更廉れん价易得え，故こ氯是ぜ较理想りそう的てき离去基もと团。与あずか之これ反はん应的有ゆう机つくえ金属きんぞく化合かごう物ぶつ还有锡、锌或ある硼。

操作そうさ条件じょうけん

虽然大だい多た偶联反はん应涉及的试剂都と对水和わ空そら气极其敏感かん，但ただし不可ふか认为所有しょゆう有ゆう机つくえ偶联反はん应需要よう绝对的てき无水无氧条件じょうけん。有ゆう些有机つくえ钯介导的反はん应就可か在ざい水溶液すいようえき中ちゅう，用よう三さん苯基膦和かず硫酸りゅうさん制せい备的磺化膦试剂反应。^[7]总体来らい讲，大だい多た这类反はん应都藉不饱和金属きんぞく络合物ぶつ反はん应，而这些络合ごう物ぶつ都と不ふ满足18共きょう价电子こ的てき稳定结构，故こ空そら气中的てき氧气能のう影かげ响偶联反应。

类型

常つね见偶联反应有：

反はん应名称めいしょう	发现年代ねんだい	反はん应物A		反はん应物B		类型	催化剂	备注
武たけ兹反应（Wurtz reaction）	1855	R－X	sp³	R－X	sp³	自身じしん		以鈉消しょう除じょ反はん应物的てき卤原子げんし
格かく拉ひしげ泽偶联反应（Glaser coupling）	1869	RC≡CH	sp	RC≡CH	sp	自身じしん	Cu	氧气作さくH受体
乌尔曼反应（Ullmann reaction）	1901	Ar－X	sp²	Ar－X	sp²	自身じしん	Cu	高温こうおん
冈伯格かく－巴ともえ克かつ曼反应	1924	Ar－H	sp²	Ar－N₂X	sp²	自身じしん		需碱参与さんよ
Cadiot－Chodkiewicz偶联反はん应	1957	RC≡CH	sp	RC≡CX	sp	交叉こうさ	Cu	需碱参与さんよ
Castro－Stephens偶联反はん应	1963	RC≡CH	sp	Ar－X	sp²	交叉こうさ	Cu
吉よし尔曼试剂偶联反はん应（Gilman reagent coupling）	1967	R₂CuLi		R－X		交叉こうさ
Cassar反はん应	1970	烯烃	sp²	R－X	sp³	交叉こうさ	Pd	需碱参与さんよ
熊田くまだ偶联反はん应（Kumada coupling）	1972	Ar－MgBr	sp²／sp³	Ar－X	sp²	交叉こうさ	Pd或あるNi
赫克反はん应（Heck reaction）	1972	烯烃	sp²	R－X	sp²	交叉こうさ	Pd	需碱参与さんよ
薗その头偶联反应（Sonogashira coupling）	1975	RC≡CH	sp	R－X	sp³／sp²	交叉こうさ	Pd和わCu	需碱参与さんよ
根岸ねぎし偶联反はん应（Negishi coupling）	1977	R－Zn－X	sp³／sp²／sp	R－X	sp³／sp²	交叉こうさ	Pd或あるNi
施ほどこせ蒂勒反はん应（Stille coupling）	1978	R－SnR₃	sp³／sp²／sp	R－X	sp³／sp²	交叉こうさ	Pd
铃木反はん应（Suzuki reaction）	1979	R－B(OR)₂	sp²	R－X	sp³／sp²	交叉こうさ	Pd	需碱参与さんよ
Hiyama偶联反はん应	1988	R－SiR₃	sp²	R－X	sp³／sp²	交叉こうさ	Pd	需碱参与さんよ
Buchwald–Hartwig偶联反はん应	1994	R₂N－R SnR₃	sp	R－X	sp²	交叉こうさ	Pd	N－C偶联反はん应
福山ふくやま偶联反はん应（Fukuyama coupling）	1998	RCO(SEt)	sp²	R－Zn－I	sp³	交叉こうさ	Pd
偶联反はん应一览. 参考さんこう文献ぶんけん见子页面

杂项反はん应

一いち种基于芳よし基もと卤代烃和全わぜん氟代苯的钯－催化偶联反はん应由基もと思おもえ·法ほう纽（Keith Fagnou）和かず其同事ごと所しょ报道。对于这种缺かけ电子的まと芳よし环来讲，这类官能かんのう团化反はん应很不ふ寻常。^[17]

应用

许多偶联反はん应已经广泛的应用于制せい药工业^[18]和わ相しょう关的工こう业原料りょう^[19]。

参まいり见

钯催化か偶联反はん应

参考さんこう资料

^ Organic Synthesis using Transition Metals Rod Bates ISBN 978-1-84127-107-1
^ New Trends in Cross-Coupling: Theory and Applications Thomas Colacot (Editor) 2014 ISBN 978-1-84973-896-5
^ The Nobel Prize in Chemistry 2010 - Richard F. Heck, Ei-ichi Negishi, Akira Suzuki. NobelPrize.org. 2010-10-06 [2010-10-06]. （原始げんし内容ないよう存そん档于2012-10-26）.
^ 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
^ Hartwig, J. F. Organotransition Metal Chemistry, from Bonding to Catalysis; University Science Books: New York, 2010. ISBN 189138953X
^ 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
^ ^7.0 ^7.1 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.
^ 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
^ 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
^ 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
^ 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
^ Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds Norio. Miyaura, Akira. Suzuki Chem. Rev., 1995, 95 (7), pp 2457–2483 doi:10.1021/cr00039a007
^ 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
^ 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
^ 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
^ 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
^ 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.
^ R.H. Crabtree, The Organometallic Chemistry of the Transition Metals 4th Ed.
^ Organotransition Metal Chemistry: From Bonding to Catalysis John Hartwig

[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]. （原始げんし内容ないよう存そん档于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

[#1-7] 7.0 ^7.1 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

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