Buchwald 反應(yīng)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(duì)碘代芳烴反應(yīng)尤其突出；1,4-二氧六環(huán)，由于其自身毒性，有時(shí)會(huì)用Bu2O代替；叔丁醇也會(huì)被用到，如果反應(yīng)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(yīng)需在無水無氧條件下進(jìn)行，一般回流反應(yīng)。操作基本相似。
1、 Buchwald 反應(yīng)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(yīng)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(yīng)的L1或L4與苯乙胺和氯化鈀絡(luò)合物，如
有關(guān)此反應(yīng)的相關(guān)介紹
Buchwald–Hartwig芳胺化反應(yīng)
Buchwald–Hartwig芳胺化反應(yīng)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(yīng)。此反應(yīng)的主要特點(diǎn)是利用催化量的鈀和富電子配體進(jìn)行催化反應(yīng)。另外強(qiáng)堿（如叔丁醇鈉）對(duì)于催化循環(huán)是至關(guān)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(duì)于溴化物反應(yīng)需要更高的溫度。后者在常溫下即能反應(yīng)，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(yīng)生成苯胺。采用和溴苯類似的反應(yīng)條件，對(duì)于中性或富電子的三氟甲磺酸酯都有較好收率。但對(duì)于缺電子的三氟甲磺酸酯收率卻較低，原因是叔丁醇鈉會(huì)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(yīng)還對(duì)伯胺和仲胺有一定的選擇性，優(yōu)先和伯胺反應(yīng)。
配體對(duì)反應(yīng)的影響很大，不同的配體收率差別很大。而且針對(duì)什么樣的底物用什么配體，沒有一個(gè)清楚的規(guī)律，這也是Buchwald-Hartwig芳胺化反應(yīng)一個(gè)最大的遺憾。因此有時(shí)對(duì)不同的底物在做反應(yīng)時(shí)經(jīng)常要對(duì)反應(yīng)的配體進(jìn)行優(yōu)化。
Buchwald 反應(yīng)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(huán)。
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(duì)于底物為苯環(huán)類化合物，溶解性較好化合物，常用甲苯作溶劑；對(duì)于雜環(huán)類反應(yīng)，溶解性不好的底物常用1，4-二氧六環(huán)作溶劑。溴化物與胺的偶聯(lián)常用t-BuOK或t-BuONa作堿，三氟甲磺酸酯與胺的反應(yīng)常用Cs2CO3作堿。
反應(yīng)需在無水無氧條件下進(jìn)行，一般回流反應(yīng)。操作基本相似。
反應(yīng)機(jī)理
催化循環(huán)
反應(yīng)實(shí)例
參考文獻(xiàn)
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(dǎo)下在加州大學(xué)伯克利分校獲得Ph.D. 。2006年他從耶魯大學(xué)轉(zhuǎn)到了伊利諾伊大學(xué)厄巴納―香檳分校，2011年后又從UI-UC轉(zhuǎn)到了加州大學(xué)伯克利分校從事研究工作。Hartwig 和 Buchwald分別獨(dú)立的發(fā)現(xiàn)了此反應(yīng)。）
(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(dǎo)下在哈佛大學(xué)獲得Ph.D.。他現(xiàn)在是麻省理工大學(xué)的教授。） (b) Palucki, M.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 10333-10334.
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5. Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805-818. (Review).
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編譯自：J.J. Li, Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications, Buchwald–Hartwig amination，page 91-94.
