氨基酸促进的铜（Ⅰ）催化的乌尔曼反应的研究

【作者】 张慧；

【导师】 马大为；

【作者基本信息】 复旦大学 ， 有机化学， 2005， 博士

【副题名】芳基卤化物与硫酚（醇）、胺、含氮杂环交叉偶联反应的研究

【摘要】 芳基碳—硫键、芳基碳—氮键广泛存在于许多有生理活性的天然产物、药物、农药以及具有电子性能的材料中,因此芳基碳—硫键、芳基碳—氮键的构建方法,对合成含有这些结构单元的天然产物、药物、农药、材料等非常重要,从而一直是有机化学家重点研究的课题之一。 乌尔曼反应是形成芳基碳—硫键、碳—氮键的重要方法。它是通过芳基卤化物在铜试剂催化下,直接与硫酚、硫醇、胺、含氮杂环等亲核试剂一步反应得到偶联产物。其优点是所用催化剂价廉易得,反应一步完成,有应用在工业上大规模生产的重要意义。但是由于传统乌尔曼反应有常须在超过150℃的高温,强碱存在,以及催化剂过量的条件下反应,产物收率不高等缺点,在很长一段时期内,应用与研究都处在停顿阶段。 我们小组根据以前对芳基卤化物与氨基酸偶联反应的研究结果,通过对影响反应的诸多条件如溶剂、温度、浓度、碱、催化剂、添加剂(配体)等的研究,发现氨基酸可作为配体,与碘化亚铜一起组成催化体系,在低于或等于110℃的温和反应温度下,用催化量的氨基酸(20 mol%)与碘化亚铜(10 mol%)组成的催化体系,能成功催化芳基卤化物与含杂原子亲核试剂的偶联,产物收率在多数情况下80-100%。 本论文阐述了反应条件的优化过程,并将因此得到的催化体系分别用于: 1、芳基碘化物与硫酚、硫醇的偶联反应。发现带有吸电子基、给电子基、或中性基团的芳基碘代物均能在80℃与硫酚发生偶联反应,得到很好的收率;但对硫醇,仅带有吸电子基的碘代物能给出较好的收率。 2、芳基卤化物,杂环卤化物与一级、二级脂肪胺,芳胺等的偶联反应。发现带有吸电子基、给电子基、中性基团的芳基碘代物、溴代物均能以很好的收率,在40—90℃与一级、二级环状脂肪胺发生偶联;空间位阻大的底物则需在较高温度110℃下完成反应。杂环溴化物与一级、二级环状脂肪胺可在低于或等于90℃的条件下顺利地以高收率得到偶联产物。芳基氯化物与一级脂肪胺在70℃实现了分子内偶联。芳基碘代物、溴代物与芳胺的偶联则仅限于与富电子芳胺的反应取得了成功。更多还原

【Abstract】 S-aryl sulfides, N-aryl amines, N-aryl pyrroles, N-aryl indoles, N-aryl imidazoles, and N-aryl pyrazoles are prevalent in compounds that are of biological, pharmaceutical and materials interest.Copper-catalyzed Ullmann type reactions are traditional methods to assemble these compounds. However, the harsh reaction conditions (high temperatures, strong bases, stoichiometric amounts of copper or copper salts, long reaction times) are needed to effect these transformations. These procedures usually gave moderate yields.In order to overcome these drawbacks, our group, based on the previous work about the coupling reaction of aryl halides with a-amino acids, got the conclusion that amino acids could be used as additives to promote Ullmann-type reactions. Therefore, after optimization of reaction conditions such as solvents, temperatures, bases, ligands, copper reagents, the ratio of copper reagents and ligands etc., we found an effective catalytic system: 20 mol% N-methylglycine, L-proline or N,N-dimethylglycine/10 mol% Cul. In this thesis, we wish to describe the aryl C-N or C-S formation under the action of these catalytic systems.In the first chapter, we investigated the coupling of aryl iodides with thiols and found that under catalysis of CuI/L-proline both electron-rich and electron-poor aryl iodides could react with phenyl thiol to give the corresponding coupling products in good to excellent yields. However, good yields were only seen when electron-poor aryl iodides coupled aliphatic thiols.In the second chapter, we studied the coupling reaction of aryl halides with amines. CuI-catalyzed coupling reaction of electron-deficient aryl iodides with aliphatic primary amines completes at 40 °C under the promotion of N-methylglycine. Using L-proline as the promoter, coupling reaction of aryl iodides or aryl bromides更多还原