面向不对称加氢反应的氢源可再生分子反应器的研究

Asymmetric hydrogenation of unsaturated organic compounds, such as olefins, carbonyls, and imines, is currently becoming a standard procedure in both academic laboratories and industrial applications. In traditional asymmetric hydrogenation processes, hydrogen gas is typically used as the reducing agent with transition metal-based chiral catalysts, while in the case of asymmetric transfer hydrogenation, isopropanol and formic acid are the most frequently employed hydrogen sources. Although most of these transition metal-catalyzed processes show high reactivity and selectivity, some of them still suffer from considerable drawbacks including limited substrate scope, difficulty in catalyst separation and recycling as well as the danger in handling high pressure of hydrogen gas. The reduced nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) play great roles in reduction−oxidation metabolism in a couple of the most important coenzymes found in living cells. NAD(P)H model have been widely and successfully used as a hydrogen source in the biomimetic asymmetric transfer hydrogenation of double-bond-containing in the presence of organocatalysts. But, developing a biomimetic asymmetric hydrogenation system that simultaneously involves an asymmetric reduction process and the regeneration of hydrogen sources is still a great challenge in the field of NAD(P)H mimics. In this project, dihydropyridine amido group (DHPA) as the key structure in NAD(P)H models plays an important part in the hydride transfer process, the incorporating of a DHPA group within the ligand backbone as the hydrogen source is expected as an powerful approach to mimic the activity of enzymes. At the same time, the introduction of chiral pyrrole groups used as pyrrolidiinium catalyst to investigate about the activity of asymmetric hydrogenation of α,β-unsaturated aldehyde compounds. And special transition metal ions which were popularly used with mimicking hydrogenase (Co and Ni) complexes will be incorporated as the nodes and catalytic centers into suitable coordination environment. With choosing suitable photosensitizer, this project will explore photo drive hydrogen production processes of the supermolecule systems. It provides hydrogen source for regeneration of the NAD(P)H model. Based on the above research, by carefully matching the redox potential between the metal catalytic centre and the photosensitizer to regulate reaction rate of the photo drive hydrogen production, matching the reaction rate of the asymmetric hydrogenation, and establish the theoretical foundation for realizing the asymmetric hydrogenation reaction of regeneration hydrogen source.

不对称催化加氢反应在手性药物合成和精细化工品生产中都占有非常重要的地位。传统催化加氢过程中，手性金属配合物催化剂难制备且不易分离，高压氢气为氢源具有高危险性。因此，有机催化剂和NAD(P)H模拟物氢源被广泛应用于不对称催化加氢反应，但NAD(P)H模拟物的再生利用成为其走向应用的一个巨大挑战。本项目以NAD(P)H活性中心为母体设计具有特定对称性的有机配体，与具有良好氧化还原活性的钴、镍等金属离子构筑金属-有机笼状分子反应器，引入手性吡咯基团作为亚胺离子催化剂，NAD(P)H活性中心作为氢源，研究探讨α,β不饱和醛的不对称催化加氢反应活性；选择合适的光敏剂考察体系的放氢过程，为NAD(P)H活性中心的再生提供还原剂。通过合理的设计金属离子中心的配位环境，调控超分子体系的氧化还原电位，调节体系的的放氢速率，匹配催化加氢反应速率，为实现模拟物氢源可再生循环利用的不对称催化加氢反应提供理论依据。

受自然界的启发，在温和条件下，利用清洁能源和绿色溶剂进行催化合成一直以来都是化学家努力的方向。为了匹配生物酶体系的高效和高选择性，化学家选择具有明确稳定疏水空腔（孔道）结构的金属-有机超分子体系模拟生物酶活性位点催化特殊化学转化。在国家自然科学基金委员会青年基金项目“面向不对称加氢反应的氢源可再生分子反应器的研究”的资助下，构建具有氢化酶催化中心配位环境的超分子结构，匹配染料激发态和催化中心的氧化还原电位，有效加快电子的转移速率；引入具有高效传递电子质子功能的辅酶NAD(P)H活性中心作为氢源，选择具有良好氧化还原活性的镍离子作为节点，兼具光催化质子还原和氢化反应双功能的环状可再生超分子体系能够通过袋状空腔对底物和光敏剂分子的选择性识别作用，有效控制空腔内外反应动力学和中间体的兼容性。常温常压下，在内部完成底物氢化的同时，利用外部光催化活化质子再生氢化反应中产生的NAD(P)+，快速恢复NAD(P)H辅酶活性中心，实现了温和条件下氢源可再生利用的催化加氢反应。捕获辅酶QHQ构建主-客体超分子电荷转移复合物，在温和条件下，高效催化硝基苯加氢转化苯胺，体系的TON值达到340 000每摩尔催化剂，高效的转化效率表明金属-有机超分子体系囊括生物辅酶策略有明确的应用前景，有望作为还原剂应用于化工中硝基苯的还原。项目执行期间，在Angew. Chem. Int. Ed.、Coord. Chem. Rev.、Sci. Rep.等学术期刊发表SCI论文7篇，申请专利1件。研究成果获辽宁省自然科学学术成果奖一等奖1项（排名第一）。