铜催化环丙醇的开环三氟甲基化反应研究

发布时间：2018-05-14 19:42

本文选题：铜催化 + 环丙醇　；参考：《合肥工业大学》2016年硕士论文

【摘要】：三氟甲基基团(CF_3)是许多药物分子的重要结构单元。在药物分子中引入三氟甲基,可以有效、显著地改善药物的亲脂性、可吸收性和代谢稳定性。同时,β-取代酮在有机化学合成领域是重要的起始原料和合成中间体。比如,其可以作为烯酮的前体,也是合成稠环化合物、杂环衍生物以及二羰基化合物等的重要中间体。其中的p-三氟甲基酮是重要而又难以合成的分子,条件大多比较苛刻。传统的合成方法,如“CF_3~-”试剂与不饱和羰基化合物的亲核加成反应,具有很差的区域选择性。最近的注意力已经转移到使用“CF_3~+”试剂通过自由基过程与过渡金属结合来合成β-三氟甲基酮。众所周知,环丙醇很容易由Kulinkovich反应制得。更重要的是,环丙醇可经过有效的开环转换反应,生成β-取代基(例如：卤素、芳基、烷基等)酮。在此背景下,我们研究了铜催化的环丙醇的开环三氟甲基化反应,我们使用环丙醇来合成β-三氟甲基酮。环丙醇的开环三氟甲基化反应,不仅扩大了C-C键断裂重排三氟甲基化的概念和实用性,同时也为合成β-三氟甲基酮提供了新的路线。与此同时,我们的研究也为环丙醇的转化化学增加了一个新的研究领域。
[Abstract]:Trifluoromethyl group CF3) is an important structural unit of many drug molecules. The introduction of trifluoromethyl into the drug molecules can significantly improve the lipophilicity, absorbability and metabolic stability of the drug. At the same time, 尾-substituted ketones are important starting materials and intermediates in the field of organic chemistry synthesis. For example, it can be used as a precursor of ketene, as well as an important intermediate for the synthesis of dense ring compounds, heterocyclic derivatives and dicarbonyl compounds. Among them, p-trifluoromethyl ketones are important and difficult to synthesize, and the conditions are mostly harsh. Traditional synthesis methods, such as the nucleophilic addition reaction of "CFS 3-" reagent with unsaturated carbonyl compounds, have poor regioselectivity. Recent attention has shifted to the synthesis of 尾 -trifluoromethyl ketones by free radical processes combined with transition metals using the "CFS 3 ~" reagent. It is well known that cyclopropanol is easily prepared by Kulinkovich reaction. More importantly, cyclopropanol can undergo an efficient ring-opening conversion reaction to produce 尾-substituted ketones (for example, halogen, aryl, alkyl, etc.). In this context, we studied the cyclic trifluoromethylation of cyclopropanol catalyzed by copper. We used cyclopropanol to synthesize 尾 -trifluoromethyl ketone. The ring-opening trifluoromethylation of cyclopropanol not only expands the concept and practicability of C-C bond breaking rearrangement trifluoromethylation, but also provides a new route for the synthesis of 尾 -trifluoromethyl ketones. At the same time, our research also adds a new research field for the conversion chemistry of cyclopropanol.
【学位授予单位】：合肥工业大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O621.251

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