过渡金属催化瞬态导向C-H键活化构建C-P键反应及其机理研究

Organophosphorus compounds are widely used in medicine, pesticide, materials and organic synthesis. It is important to developing green, efficient and controllable methods for the construction of these compounds. This project intends to introduce transition-metal catalyzed C-H bond activation via transient directing groups for the construction of C-P bond between aldehydes or ketones and P(O)-H compounds. From the start with the study of reaction mechanism, explore the catalytic coupling reaction of aldehydes or ketones selective C-H phosphorylation, develop new catalytic system for transient directing functionalizations of inert C-H bond. Based on the special chemical characters of P(O)-H compound, amines with special flames will be designed to react with aldehydes or ketones forming transient imine group, which can stabilize the critical reaction intermediates. The structures of the isolated reaction intermediates are characterized by NMR analysis and X-ray single crystal diffraction, and the chemical properties studies for them are carried out to reveal the real process of the reactions. Further research will be conducted to achieve the precise control of the reaction by modulation of reaction conditions and catalytic system. This project will provide valuable reference for the development and application of the transition-metal catalyzed inert C-H bond activation via transient directing group and new thinking for C-P bond construction. Hence, this proposal has important scientific value and practical significance.

有机膦化合物在医药、农药、材料、有机合成等领域中应用广泛。开发高效、绿色、精准构建C-P键的新方法对合成高附加值的有机膦化合物具有重要意义。本项目以醛或酮为底物，结合P(O)-H化合物，运用过渡金属催化瞬态导向C-H键活化策略构建C-P键。从机理研究入手，对醛或酮选择性C-H键磷酰基化的催化偶联反应进行探索，设计开发新型过渡金属催化体系用于瞬态导向C-H键官能团化反应。通过设计合成特殊骨架的有机胺分子与醛或酮形成瞬态亚胺导向基团，稳定、分离反应的有机金属中间体，结合核磁共振和单晶衍射等技术手段研究其物理化学性质，从而揭示瞬态导向碳氢磷酰基化反应的机理。在此基础上，调变反应条件和催化体系以实现对反应的精密控制。本项目的实施为过渡金属催化瞬态导向C-H键官能团化的拓展与应用提供重要的理论参考，为C-P键的精准构建提供新思路，具有重要的科学价值和现实意义。

含C-P键的有机膦化合物在医药、农药、材料及有机合成领域中具有广泛应用，开发其高效、绿色、精准合成的新方法具有重要意义。本项目主要从机理研究入手，围绕高附加值的有机膦化合物的合成新方法开展工作，通过对反应的精密控制，建立了几种有机膦化合物绿色、高效、简易合成的新方法。（1）采用镍催化实现了单氟取代的芳烃C-F键活化与P(O)H化合物交叉偶联构建C-P键，反应无需外加配体，且反应底物活性决定了反应的关键中间体的形成。（2）在碱的促进作用下，实现了活性较大的氟代芳烃与P(O)H化合物的亲核取代反应，高效合成含有C-P键的有机膦化合物；（3）在碱的促进作用下，实现了三氟甲烷磺酸酯类化合物的选择性S-O键断裂与P(O)H化合物反应制备重要的O-芳基次膦酸酯；（4）在三乙胺的促进作用下，实现了P(O)-OH化合物与氯代烷烃的取代反应，反应无需外加溶剂，简单高效，为重要的含氯有机磷酸酯的合成提供了新思路。以上研究结果为有机膦化合物的合成提供了新思路，对精细有机磷化学品的合成与开发提供重要的理论基础和数据支持。