氮杂环卡宾与中心手性金属配合物共催化的单电子转移自由基反应研究

To develop efficient synthetic strategies for rapid and green access to functional molecules is the central goal in modern organic chemistry. In recent years great success has been achieved with N-heterocyclic carbene (NHC) catalyzed reactions based on lone pair electron transfer. In contrast, single electron transfer (SET) radical reactions were much less developed. On the other hand, chiral-at-metal Lewis acid complexes would be of significant value in the field of asymmetric catalysis, in particular in combination with visible-light-induced redox chemistry, which has already resulted in novel strategies for asymmetric synthesis of chiral molecules. Inspired by the SET process in the biological systems, we realized the NHC catalyzed radical coupling reaction of beta-substituted nitroethylenes and enantioselective beta-hydroxylation of enals. Based on our previous work, our goal is to develop new activation modes via NHC & chiral-at-metal complexe catalyzed SET radical reactions. Our study will generate new fundamental knowledge of asymmetric catalysis radical process. By studying the reactions in both kinetic and thermodynamic ways, we will be able to effectively control the process of these radical reactions. Our proposed research will also provide novel synthetic strategies for rapid construction of both small functional molecules and core structures of sophisticated molecules.

发展高效的合成策略，进而简洁、绿色环保地构建功能性分子，是当代有机化学研究的核心目标。近年来，基于氮杂环卡宾（NHC）催化实现的电子对转移的反应已经取得令人瞩目的成就，但是，通过单电子转移途径实现的自由基反应却鲜见报道；另一方面，中心手性金属配合物因其路易斯酸性，以及和光致氧化还原反应的有效结合，在不对称催化领域的作用日渐突出，为手性分子的合成提供全新的基于单电子转移的合成策略。受生物系统内单电子转移过程的启发，我们实现了基于NHC催化的硝基乙烯类化合物的偶联反应，以及α,β-不饱和醛的β-羟基化反应。在此基础之上，我们的目标是利用NHC与中心手性金属配合物共同催化，获得全新的基于单电子转移途径的催化活化模式，为不对称催化的自由基反应提供新的理论知识；通过对反应动力学及热力学的深入研究，实现对反应过程的有效控制；研究也会为功能性小分子或复杂分子核心骨架的快速构建提供新的合成策略。

为了实现功能小分子或复杂分子骨架的高效快速构建，我们通过中心手性金属配合物催化结合其他活化模式的手段，致力于开发新的不对称催化反应和合成方法。我们在这一策略指导下，实现了一些新颖的不对称反应，如可见光催化、双金属协同催化、金属和有机小分子协同催化等，这些成果极大地拓展了手性金属配合物在不对称催化中的应用范围。同时，借助于新开发的手性配体，或者通过调节金属与特定底物之间的螯合作用，实现了一些简单原料（例如，脂肪酸、氨基酸、非定向芳烃、内烯烃等）的区域和立体选择性碳氢键官能化，高效地合成了一系列高附加值分子，如三甲基锁型触发器、无偏全碳三取代或四取代烯烃和后期功能化肽。