非活化C(sp3)-H键的三氟甲基化

项目名称： 非活化C(sp3)-H键的三氟甲基化

项目编号： No.21502214

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 数理科学和化学

项目作者： 林锦鸿

作者单位： 中国科学院上海有机化学研究所

项目金额： 21万元

中文摘要： 三氟甲基化是近年来有机氟化学领域的研究热点之一，目前已发展了多种三氟甲基化方法来构建各种C-CF3键。常用的C(sp3)-CF3键的构建方法一般需要对底物进行预官能团化，比较繁琐、适用性有限。相比之下，C(sp3)-H 键的三氟甲基化显得更加直接有效。已知的C(sp3)-H键的三氟甲基化方法中，C(sp3)-H键都已被高度活化，具有较大的局限性。我们将发展新方法实现非活化C(sp3)-H键的三氟甲基化，展开以下几方面的工作：过渡金属催化的非活化C(sp3)-H键的三氟甲基化；无导向作用、非活化C(sp3)-H键的三氟甲基化；非活化C(sp3)-H键的不对称三氟甲基化。过渡金属催化的方法可通过导向基团的导向作用控制区域选择性。无导向作用下的反应不但C-H键难以断裂，区域选择性也很难控制，因此选择合理的方法就很重要。在深入认识非活化C(sp3)-H键三氟甲基化的反应规律之后将研究其不对称反应。

中文关键词： 三氟甲基化；非活化C(sp3)-H键；催化；不对称三氟甲基化

英文摘要： Determined efforts have been directed towards the exploration of efficient methods for trifluoromethylation in the past years, and the outstanding accomplishments in this field have allowed for the convenient construction of various C-CF3 bonds. Although a number of valuable approaches have been developed to construct C(sp3)-CF3 bond, they suffer from the need to prefunctionalize substrates. In contrast, C(sp3)-H trifluoromethylation protocol is straightforward and attractive. The C(sp3)-H trifluoromethylation has been recently studied, but the reported methods are limited to the trifluoromethylation of highly activated C(sp3)-H bond. This research program will focus on the trifluoromethylation of unactivated C(sp3)-H bond, including transition metal-catalyzed unactivated C(sp3)-H bond trifluoromethylation, trifluoromethylation of unactivated C(sp3)-H bond without a directing group, and asymmetric C(sp3)-H bond trifluoromethylation. The regioselectivity will be a significant issue for the C(sp3)-H bond trifluoromethylation. Transition metal provides an opportunity to control the selectivity by coordinating to a directing group in the substrate. Trifluoromethylation of the unactivated C(sp3)-H bond without a directing group will be a great challenge, not only because the C-H bond is inert, but also because the regioselectivity is difficult to be controlled. Therefore, it is important to use effective methods to realize this transformation. After deeply studying the trifluoromethylation of the unactivated C(sp3)-H bond, we will further investigate its asymmetric version.

英文关键词： Trifluoromethylation;Unactivated C(sp3)-H bond ;Catalysis;Asymmetric trifluoromethylation