根岸偶聯反應

根岸偶聯反應（英語：Negishi coupling）是一個有機反應。該反應中，有機鋅試劑與鹵代烴在鎳或鈀的配合物的催化下發生偶聯，生成一個新的C－C鍵^[1]^[2]：

其中，

鹵素 X 可以是氯、溴或碘，也可以是其它的基團，如三氟甲磺酰基或乙酰氧基，而基團 R 則可以是烯基、芳基、烯丙基、炔基或炔丙基（英語：propargyl）；
鹵素 X' 同樣可以是氯、溴或碘，R' 則可以是烯基、芳基、烯丙基或者烷基；
催化劑中的金屬 M 可以是鎳或者鈀；
配體 L 可以是三苯基膦，dppe，BINAP或者雙(二苯基膦)丁烷。

用含鈀催化劑時，通常產率較高，對官能團的耐受性也比較好。

該反應以日本化學家根岸英一（日語：根岸英一／ねぎしえいいち^{Negishi Ei-ichi}）命名，根岸憑藉此貢獻得到了2010年諾貝爾化學獎。

反應機理

在這個反應中具有催化活性的是零價的金屬（M⁰）。反應整體上經過了鹵代烴對金屬的氧化加成、金屬轉移與還原消除這三步：

鹵化烴基鋅與二烴基鋅都可以作為反應物。對模型化合物的研究發現，在金屬轉移一步中，前者會生成順式的絡合物從而能很快地發生還原消除的後續步驟，生成產物。而後者則會生成反式的絡合物，必須經過緩慢的順反異構體異構化過程^[3]。

最新進展

Negishi偶聯反應在最近的多個合成中有應用，包括從2-溴吡啶合成2,2'-聯吡啶（所用的催化劑為四(三苯基膦)合鈀(0)）^[4]，從鄰甲苯基氯化鋅和鄰位取代的碘苯（仍以四(三苯基膦)合鈀(0)作催化劑）合成聯苯衍生物^[5]，以及從1-癸炔與(Z)-1-碘-1-己烯合成5,7-十六碳二烯^[6]。

Negishi偶聯還用於六(二茂鐵)苯的合成，如下式所示^[7]：

這個反應用六碘苯與雙(二茂鐵)鋅為原料，以三(二亞苄基丙酮)二鈀(0)（英語：tris(dibenzylideneactone)dipalladium(0)）作催化劑，在四氫呋喃中反應。產率僅為4%，這與芳環周圍的位阻有關。

Negishi反應的一種最新的變化形式是先用2-氯-2-苯基苯乙酮1來氧化鈀，生成含有OPdCl基團的鈀配合物。該化合物隨後發生雙金屬轉移反應，接受分別來自有機鋅試劑2和有機錫試劑3的兩個烴基，如下式所示^[8]：

外部連結

organic-chemistry.org上的Negishi偶聯反應（頁面存檔備份，存於網際網路檔案館）
根岸偶聯反應（Negishi coupling）（頁面存檔備份，存於網際網路檔案館）

參考文獻

^ Anthony O. King, Nobuhisa Okukado and Ei-ichi Negishi. Highly general stereo-, regio-, and chemo-selective synthesis of terminal and internal conjugated enynes by the Pd-catalysed reaction of alkynylzinc reagents with alkenyl halides. Journal of the Chemical Society Chemical Communications. 1977: 683. doi:10.1039/C39770000683.
^ Strategic Applications of Named Reactions in Organic Synthesis Laszlo Kurti, Barbara Czako Academic Press (March 4, 2005) ISBN 0-12-429785-4
^ Juan A. Casares, Pablo Espinet, Beatriz Fuentes, and Gorka Salas. Insights into the Mechanism of the Negishi Reaction: ZnRX versus ZnR2 Reagents. Journal of the American Chemical Society. 2007, 129: 3508. doi:10.1021/ja070235b.
^ Adam P. Smith, Scott A. Savage, J. Christopher Love, and Cassandra L. Fraser (2004). "Synthesis of 4-, 5-, and 6-methyl-2,2'-bipyridine by a Negishi cross-coupling strategy: 5-methyl-2,2'-bipyridine". Org. Synth.; Coll. Vol. 10: 517.
^ Ei-Ichi Negishi, Tamotsu Takahashi, and Anthony O. K (1993). "Synthesis of biaryls via palladium-catalyzed cross-coupling: 2-methyl-4'-nitrobiphenyl". Org. Synth.; Coll. Vol. 8: 430.
^ Ei-Ichi Negishi, Tamotsu Takahashi, and Shigeru Baba (1993). "Palladium-catalyzed synthesis of conjugated dienes". Org. Synth.; Coll. Vol. 8: 295.
^ Yong Yu, Andrew D. Bond, Philip W. Leonard, Ulrich J. Lorenz, Tatiana V. Timofeeva, K. Peter C. Vollhardt, Glenn D. Whitener and Andrey A. Yakovenko. Hexaferrocenylbenzene. Chemical Communications. 2006: 2572. doi:10.1039/b604844g.
^ Yingsheng Zhao, Haibo Wang, Xiaohui Hou, Yanhe Hu, Aiwen Lei, Heng Zhang, and Lizheng Zhu. Oxidative Cross-Coupling through Double Transmetallation: Surprisingly High Selectivity for Palladium-Catalyzed Cross-Coupling of Alkylzinc and Alkynylstannanes. Journal of the American Chemical Society. 2006, 128: 15048. doi:10.1021/ja0647351.

[1] Anthony O. King, Nobuhisa Okukado and Ei-ichi Negishi. Highly general stereo-, regio-, and chemo-selective synthesis of terminal and internal conjugated enynes by the Pd-catalysed reaction of alkynylzinc reagents with alkenyl halides. Journal of the Chemical Society Chemical Communications. 1977: 683. doi:10.1039/C39770000683.

[2] Strategic Applications of Named Reactions in Organic Synthesis Laszlo Kurti, Barbara Czako Academic Press (March 4, 2005) ISBN 0-12-429785-4

[3] Juan A. Casares, Pablo Espinet, Beatriz Fuentes, and Gorka Salas. Insights into the Mechanism of the Negishi Reaction: ZnRX versus ZnR2 Reagents. Journal of the American Chemical Society. 2007, 129: 3508. doi:10.1021/ja070235b.

[4] Adam P. Smith, Scott A. Savage, J. Christopher Love, and Cassandra L. Fraser (2004). "Synthesis of 4-, 5-, and 6-methyl-2,2'-bipyridine by a Negishi cross-coupling strategy: 5-methyl-2,2'-bipyridine". Org. Synth.; Coll. Vol. 10: 517.

[5] Ei-Ichi Negishi, Tamotsu Takahashi, and Anthony O. K (1993). "Synthesis of biaryls via palladium-catalyzed cross-coupling: 2-methyl-4'-nitrobiphenyl". Org. Synth.; Coll. Vol. 8: 430.

[6] Ei-Ichi Negishi, Tamotsu Takahashi, and Shigeru Baba (1993). "Palladium-catalyzed synthesis of conjugated dienes". Org. Synth.; Coll. Vol. 8: 295.

[7] Yong Yu, Andrew D. Bond, Philip W. Leonard, Ulrich J. Lorenz, Tatiana V. Timofeeva, K. Peter C. Vollhardt, Glenn D. Whitener and Andrey A. Yakovenko. Hexaferrocenylbenzene. Chemical Communications. 2006: 2572. doi:10.1039/b604844g.

[8] Yingsheng Zhao, Haibo Wang, Xiaohui Hou, Yanhe Hu, Aiwen Lei, Heng Zhang, and Lizheng Zhu. Oxidative Cross-Coupling through Double Transmetallation: Surprisingly High Selectivity for Palladium-Catalyzed Cross-Coupling of Alkylzinc and Alkynylstannanes. Journal of the American Chemical Society. 2006, 128: 15048. doi:10.1021/ja0647351.

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