A Guide to Sonogashira Cross-Coupling Reactions: The Influence of Substituents in Aryl Bromides, Acetylenes, and Phosphines
A Guide to Sonogashira Cross-Coupling Reactions: The Influence of Substituents in Aryl Bromides, Acetylenes, and Phosphines
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DOI：
10.1021/jo202644g
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发表时间：
2012-03-16
影响因子：
3.6
通讯作者：
Plenio, Herbert
中科院分区：
文献类型：
--
作者：
Schilz, Marc;Plenio, Herbert
168种不同Pd/ cu催化5种芳基乙炔（苯基乙炔、1-乙基-2-乙苯、1-乙基-2,4,6-R-3-苯（R = Me, Et, i-Pr））和Me3SiCCH与7种芳基溴（3种2-R-溴苯（R = Me, Et, i-Pr））的Sonogashira交叉偶联反应转化时间数据；用定量气相色谱法测定了2,6-Me-2-溴苯和3种2,4,6-R-3-溴苯（R = Me, Et, i-Pr）与4种不同的膦（P-t-Bu-3, t-Bu2PCy, t-BuPCy2, PCy3）的含量。芳基溴、乙炔和膦中取代基的立体电子性质与Sonogashira反应的性能相关。结果表明，最活跃的Pd/PR3配合物的Sonogashira转化性质主要由乙炔的空间体积决定；理想的催化剂是：Pd/P-t-Bu-3或Pd/t-Bu2PCy用于空间要求不高的苯乙炔，Pd/t-BuPCy2用于2-和2,6取代芳基乙炔或Me3SiCCH， Pd/t- bupcy3用于体积极大的乙炔和芳基溴。具有2-或2,6取代基的富电子和立体要求高的芳基溴比4取代的芳基溴需要更多的催化剂。在两个芳基环中的一个环上有庞大基团的甲苯的合成最好是把立体体放在芳基乙炔上，芳基乙炔也是吸电子取代基的最佳位置。
The conversion time data for 168 different Pd/Cu-catalyzed Sonogashira cross-coupling reactions of five arylacetylenes (phenylacetylene; 1-ethynyl-2-ethylbenzene; 1-ethynyl-2,4,6-R-3-benzene (R = Me, Et, i-Pr)) and Me3SiCCH with seven aryl bromides (three 2-R-bromobenzenes (R = Me, Et, i-Pr); 2,6-Me-2-bromobenzene and three 2,4,6-R-3-bromobenzenes (R = Me, Et, i-Pr)) with four different phosphines (P-t-Bu-3, t-Bu2PCy, t-BuPCy2, PCy3) were determined using quantitative gas chromatography. The stereoelectronic properties of the substituents in the aryl bromides, acetylenes, and phosphines were correlated with the performance in Sonogashira reactions. It was found that the nature of the most active Pd/PR3 complex for a Sonogashira transformation is primarily determined by the steric bulk of the acetylene; ideal catalysts are: Pd/P-t-Bu-3 or Pd/t-Bu2PCy for sterically undemanding phenylacetylene, Pd/t-BuPCy2 for 2- and 2,6-substituted arylacetylenes or Me3SiCCH and Pd/PCy3 for extremely bulky acetylenes and aryl bromides. Electron-rich and sterically demanding aryl bromides with substituents in the 2- or the 2,6-position require larger amounts of catalyst than 4-substituted aryl bromides. The synthesis of tolanes with bulky groups at one of the two aryl rings is best done by placing the steric bulk at the arylacetylene, which is also the best place for electron-withdrawing substituents.