钴催化自由基极性交叉氢官能团化反应研究

Due to the unique selectivity as well as great synthetic potential, the metal-catalyzed olefin hydrofunctionalization reactions via hydrogen atom transfer have become a frontier in organic chemistry. However, such transformations typically rely on intercepting an alkyl radical with a SOMOphile, which sets a fundamental limit on the scope of reactions and mechanisms for reactivity and selectivity tuning. The proposed research program addresses these challenges mechanistically by exploring the organocobalt-mediated radical-polar crossover pathway in the context of catalysis. Specifically, we propose two approaches to facilitate this process through the synergy either within a dinuclear cobalt catalyst, or between a cobalt complex and a photoredox catalyst. We envision that this study will lead to new methods for the efficient intermolecular addition of common nucleophiles to unactivated alkenes under mild conditions, and provide valuable handles for controlling the stereoselectivity of this process. Overall, we hope to significantly expand the scope of current hydrofunctionalization methodologies as well as the oxidation chemistry of organocobalt complexes, which will reveal new opportunities for precisely controlling radical reactions in a broader context.

经由氢原子转移过程的金属催化烯烃氢官能团化反应具有独特的选择性和极高的应用潜力，是当前有机化学的研究前沿之一。然而，此类反应依赖亲自由基试剂捕获自由基中间体的传统途径，从原理上限制了其适用范围和调控机制。针对这一局限，本申请项目拟从机理出发，探索催化反应中钴配合物介导的自由基-极性交叉过程。这一策略有望在保留原反应优势的同时，引入新的经由氧化官能团化的极性反应途径，并实现催化剂对该过程选择性的调控。围绕此课题，我们将分别采用双核钴配合物和钴-光氧化还原双催化体系两种独特的设计，促进自由基-极性交叉过程的进行。这一研究将为温和条件下常规亲核试剂对非活化烯烃的分子间加成提供新的高效解决方案，并为控制这一过程中的立体选择性带来可能。预期本研究将显著拓展氢官能团化反应的应用范围，突破该过程立体选择性研究的局限，丰富烷基钴配合物的化学，并为精准控制自由基反应提供新思路。

探索从烯烃出发的各种催化转化是有机合成化学的重要研究领域之一。杂原子亲核试剂对简单烷基取代烯烃的直接分子间加成（即氢官能团化）反应不仅是合成药物化学相关的支链醇/胺的衍生物最直接的手段，还对功能环烯烃单体的制备和烯烃高分子的聚合后转化有着潜在的重要意义。本项目以双金属氧化还原机制为突破口，开展了系统研究，逐步建立了一套基于绿色廉价氧化剂、高化学选择性、可拓展性高、适用于非活化烯烃的分子间氢官能团化反应体系，丰富了有机钴的化学，为调控自由基反应提供了新的思路。项目研究过程中，揭示了新型双金属氧化还原/原位生成活性高价有机钴（IV）的机制，提出了双金属机制引导的“分-合”催化策略。在该策略的指导下，完成氧化过程与氢官能团化过程的解耦，解决兼容性问题，发展了新型绿色氢酰胺化、氢胺化反应；首次实现了简单烷基自由基的类“氧化酶”型官能团化过程，并初步探索了电化学条件下对映选择性催化过程。