瞬时定位基策略在金属催化的醇或酚邻近sp3 C-H键活化官能团化中的应用

羟基的弱定位能力导致醇或酚邻近位的sp3 C-H键活化需要通过羟基引入其他定位基团，反应后再除去定位基团回到醇或酚。在多数的天然产物或药物分子中，直接的羟基是其活性官能团或重要结构的组成部分。因此，发展新型的定位基策略实现更直接的羟基邻近位置的sp3 C-H键官能团化十分必要。本项目采用新兴的瞬时定位基策略，利用有机分子催化和金属催化的协同作用，创造性利用酯交换的方式与底物羟基形成瞬时定位基——酯，研究高区域选择性醇和酚的γ或β位sp3 C-H键活化芳基化和乙酰酯化反应，并对反应对映选择性进行尝试。本项目设计合成的新型有机酯催化剂为醇和酚在催化转化中提供了除氢键外的新键合和模式。

Due to the weak coordination ability of the hydroxyl group, it cannot be directly used as a directing group during activation of sp3 C-H bonds in the vicinity of alcohols or phenols. The directing group is often required to be introduced into the molecule through the hydroxyl group in advance, and removed to return to the alcohols or the phenols after the sp3 C-H bond functionalized. However, the direct hydroxyl group is a component of their reactive functional group or important structure in most natural products or drug molecules. It is necessary to develop a novel directing group strategy to achieve more direct sp3 C-H bond activation functionalization in the vicinity of the hydroxyl group. The project creatively utilizes the transesterification method to form a transient directing group with the substrate hydroxyl group, realizing high regioselective activation of sp3 C-H bond in the vicinity alcohols and phenols with the synergistic catalysis of oragnometal and organocatalyst. The arylation and acetylation reactions were carried out to construct C-Ar bonds and C-O bonds, and the reaction enantioselectivity was investigated. The novel organic ester catalysts designed and synthesized in this project provide a new bonding mode for hydroxyl compounds during their transformation in addition to hydrogen bonding.