Buchwald 反應常用的鈀催化劑為：Pd2(dba)3, Pd(OAc)2；常用堿有：Cs2CO3， t-BuOK，t-BuONa，常用溶劑: 甲苯，二甲苯，對碘代芳烴反應尤其突出；1,4-二氧六環，由于其自身毒性，有時會用Bu2O代替；叔丁醇也會被用到，如果反應需要更高溫度，可用叔戊醇代替。

常見配體：除了BINAP，P(t-Bu)3， P(o-tolyl)3 外還有

反應需在無水無氧條件下進行，一般回流反應。操作基本相似。

1、 Buchwald 反應示例一

An oven-dried Schlenk tube was charged with cesium carbonate which had been finely ground with a mortar and pestle (1.4 eq) in a nitrogen-filled glovebox. The tube was capped with a rubber septum and removed from the glovebox. The tube was then charged with Pd2(dba)3 or Pd(OAc)2 and BINAP or PPF-OMe, and purged with argon. The aryl bromide (1.0 eq), the amine (1.2 eq), and toluene (2 mL/mmol halide) were added, and the mixture was heated to 100 oC with stirring until the starting material had been consumed as judged by GC analysis. The mixture was cooled to room temperature, diluted with ether (20 ml), filtered, and concentrated. The crude product was then purified by flash chromatography on silica gel.

2、 Buchwald 反應示例二

Pd(OAc)2 (0.025 mol%) and P(t-Bu)3 or Xantphose (0.10 mol%)(Phosphine/Pd=4:1) were added to the suspension of aryl halide (40 mmol), diarylamine (40 mmol) and NaOtBu (48 mmol) in o-xylene (60 mL) in N2 atmosphere. The mixture was heated for 3 h at 120 oC. Subsequently, it was cooled to room temeperature. H2O (60 mL) was added to it, the organic layer was separated and concentrated. The crude product was then purified by flash chromatography on silica gel or re-crystallization with MeOH/THF.

常見的條件匯總

催化劑的1或4，為相應的L1或L4與苯乙胺和氯化鈀絡合物，如

本公眾號有關此反應的相關介紹

Buchwald–Hartwig芳胺化反應

Buchwald–Hartwig芳胺化反應是非常常用的由芳基鹵代物或芳基磺酸酯制備芳胺的反應。此反應的主要特點是利用催化量的鈀和富電子配體進行催化反應。另外強堿（如叔丁醇鈉）對于催化循環是至關重要的。

一般來說碘化物的活性高于溴化物，溴化物的活性高于氯化物。氯化物相對于溴化物反應需要更高的溫度。后者在常溫下即能反應，前者則需要高溫。

與溴苯類似，苯基三氟甲磺酸酯和胺也可以反應生成苯胺。采用和溴苯類似的反應條件，對于中性或富電子的三氟甲磺酸酯都有較好收率。但對于缺電子的三氟甲磺酸酯收率卻較低，原因是叔丁醇鈉會水解掉部分三氟甲磺酸酯，用碳酸銫代替叔丁醇鈉則可避免水解，也可得到高的收率。Buchwald 反應還對伯胺和仲胺有一定的選擇性，優先和伯胺反應。

配體對反應的影響很大，不同的配體收率差別很大。而且針對什么樣的底物用什么配體，沒有一個清楚的規律，這也是Buchwald-Hartwig芳胺化反應一個最大的遺憾。因此有時對不同的底物在做反應時經常要對反應的配體進行優化。

 Buchwald 反應常用的鈀催化劑為：Pd2(dba)3,Pd(OAc)2，  常用配體為：P(t-Bu)3,BINAP, P(o-tolyl)3, Xantphos, 常用堿有：Cs2CO3， t-BuOK，t-BuONa，常用溶劑有甲苯，二甲苯，1，4-二氧六環。

催化劑和配體無固定搭配，常用效果較好的配體為Xantphos和BINAP。對于底物為苯環類化合物，溶解性較好化合物，常用甲苯作溶劑；對于雜環類反應，溶解性不好的底物常用1，4-二氧六環作溶劑。溴化物與胺的偶聯常用t-BuOK或t-BuONa作堿，三氟甲磺酸酯與胺的反應常用Cs2CO3作堿。

反應需在無水無氧條件下進行，一般回流反應。操作基本相似。

反應機理

催化循環

反應實例

參考文獻

1. (a) Paul, F.; Patt, J.; Hartwig, J. F. J. Am. Chem. Soc. 1994, 116, 5969-5970. John Hartwig earned his at the University of California-Berkeley in 1990 under the guidance of Robert Bergman and Richard Anderson. He moved from Yale University to the University of Illinois at Urbana-Champaign in 2006 and moved from UI-UC to UC Berkeley in 2011. Hartwig and Buchwald independently discovered this chemistry. （1990年John Hartwig 在Robert Bergman 和 Richard Anderson的指導下在加州大學伯克利分校獲得Ph.D. 。2006年他從耶魯大學轉到了伊利諾伊大學厄巴納―香檳分校，2011年后又從UI-UC轉到了加州大學伯克利分校從事研究工作。Hartwig 和 Buchwald分別獨立的發現了此反應。）

(b) Mann, G.; Hartwig, J. F. J. Org. Chem. 1997, 62, 5413-5418. (c) Mann, G.;

Hartwig, J. F. Tetrahedron Lett. 1997, 38, 8005-8008.

2. (a) Guram, A. S.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 7901-7902. Stephen Buchwald received his Ph.D. in 1982 under Jeremy Knowles at Harvard University. He is currently a professor at MIT. （Stephen Buchwald1982年在Jeremy Knowles 的指導下在哈佛大學獲得Ph.D.。他現在是麻省理工大學的教授。） (b) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 10333-10334.

3. Wolfe, J. P.; Buchwald, S. L. J. Org. Chem. 1996, 61, 1133-1135.

4. Driver, M. S.; Hartwig, J. F. J. Am. Chem. Soc. 1996, 118, 7217-7218.

5. Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805-818. (Review).

6. Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852-860. (Review).

7. Frost, C. G.; Mendon?a, P. J. Chem. Soc., Perkin Trans. 1 1998, 2615-2624. (Review).

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9. Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughnessy, K. H.; Alcazar-Roman, L.M. J. Org. Chem. 1999, 64, 5575-5580.

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12. Csuk, R.; Barthel, A.; Raschke, C. Tetrahedron 2004, 60, 5737-5750.

13. Janey, J. M. Buchwald–Hartwig amination, In Name Reactions for Functional Group Transformations; Li, J. J., Corey, E. J. Eds.; Wiley: Hoboken, NJ, 2007, pp 564-609.(Review).

14. Li, J. J.; Wang, Z.; Mitchell, L. H. J. Org. Chem. 2007, 72, 3606-3607.

15. Lorimer, A. V.; O’Connor, P. D.; Brimble, M. A. Synthesis 2008, 2764-2770.

16. Nodwell, M.; Pereira, A.; Riffell, J. L.; Zimmerman, C.; Patrick, B. O.; Roberge, M.; Andersen, R. J. J. Org. Chem. 2009, 74, 995-1006.

17. Witt, A.; Teodorovic, P.; Linderberg, M.; Johansson, P.; Minidis, A. Org. Process Res.Dev. 2013, 17, 672–678.

18. Raders, S. M.; Moore, J. N.; et al. Org. Chem. 2013, 78, 4649-4664.

編譯自：J.J. Li, Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications,  Buchwald–Hartwig amination，page 91-94.