Buchwald 反应的应用

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1、与吡咯及吲哚的反应 

运用 dppf作配体,取代溴苯和吡咯及吲哚也能反应,而且有很好的收率。

2、关环反应 

 分子内,溴可与伯胺或酰胺偶联高产率关环生成吡啶或吡咯。

3、卤代苯转化为苯胺反应 

二苯甲基亚胺与碘化苯或三氟甲磺酸酚酯在钯催化下可高产率生成苯基亚胺,而二 苯甲基可在羟胺,醋酸钠或盐酸,四氢呋喃条件下温和脱去。此方法为卤代苯转 化为苯胺提供个很好的途径。 

4、Buchwald 反应操作示例 

      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。 

4.1 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. 

4.2 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. 


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