Buchwald 反应常用的钯催化剂为：Pd2(dba)3, Pd(OAc)2；常用碱有：Cs2CO3， t-BuOK，t-BuONa，常用溶剂: 甲苯，二甲苯，对碘代芳烃反应尤其突出；1,4-二氧六环，由于其自身毒性，有时会用Bu2O代替；叔丁醇也会被用到，如果反应需要更高温度，可用叔戊醇代替。

常见配体：除了BINAP，P(t-Bu)3， P(o-tolyl)3 外还有

反应需在无水无氧条件下进行，一般回流反应。操作基本相似。

1、 Buchwald 反应示例一

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 反应示例二

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.

常见的条件汇总

催化剂的1或4，为相应的L1或L4与苯乙胺和氯化钯络合物，如

本公众号有关此反应的相关介绍

Buchwald–Hartwig芳胺化反应

Buchwald–Hartwig芳胺化反应是非常常用的由芳基卤代物或芳基磺酸酯制备芳胺的反应。此反应的主要特点是利用催化量的钯和富电子配体进行催化反应。另外强碱（如叔丁醇钠）对于催化循环是至关重要的。

一般来说碘化物的活性高于溴化物，溴化物的活性高于氯化物。氯化物相对于溴化物反应需要更高的温度。后者在常温下即能反应，前者则需要高温。

与溴苯类似，苯基三氟甲磺酸酯和胺也可以反应生成苯胺。采用和溴苯类似的反应条件，对于中性或富电子的三氟甲磺酸酯都有较好收率。但对于缺电子的三氟甲磺酸酯收率却较低，原因是叔丁醇钠会水解掉部分三氟甲磺酸酯，用碳酸铯代替叔丁醇钠则可避免水解，也可得到高的收率。Buchwald 反应还对伯胺和仲胺有一定的选择性，优先和伯胺反应。

配体对反应的影响很大，不同的配体收率差别很大。而且针对什么样的底物用什么配体，没有一个清楚的规律，这也是Buchwald-Hartwig芳胺化反应一个最大的遗憾。因此有时对不同的底物在做反应时经常要对反应的配体进行优化。

 Buchwald 反应常用的钯催化剂为：Pd2(dba)3,Pd(OAc)2，  常用配体为：P(t-Bu)3,BINAP, P(o-tolyl)3, Xantphos, 常用碱有：Cs2CO3， t-BuOK，t-BuONa，常用溶剂有甲苯，二甲苯，1，4-二氧六环。

催化剂和配体无固定搭配，常用效果较好的配体为Xantphos和BINAP。对于底物为苯环类化合物，溶解性较好化合物，常用甲苯作溶剂；对于杂环类反应，溶解性不好的底物常用1，4-二氧六环作溶剂。溴化物与胺的偶联常用t-BuOK或t-BuONa作碱，三氟甲磺酸酯与胺的反应常用Cs2CO3作碱。

反应需在无水无氧条件下进行，一般回流反应。操作基本相似。

反应机理

催化循环

反应实例

参考文献

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的指导下在加州大学伯克利分校获得Ph.D. 。2006年他从耶鲁大学转到了伊利诺伊大学厄巴纳―香槟分校，2011年后又从UI-UC转到了加州大学伯克利分校从事研究工作。Hartwig 和 Buchwald分别独立的发现了此反应。）

(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 的指导下在哈佛大学获得Ph.D.。他现在是麻省理工大学的教授。） (b) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 10333-10334.

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