Innovative Tools for Chemical Synthesis: Metal-Hydride Catalysis, Medicinal Motifs, and Molecular Probes

项目摘要 有机合成的研究和培训影响到需要设计和建造的所有科学领域 分子体系结构。该项目将推进催化方法，包括氢酰化和 氢胺化，作为一种吸引人的强有力的化学合成工具。提出的耦合方法有 现代和创新，因为它们依赖于常见的官能团(例如，醛、胺)来生成 来自不饱和伙伴的新的碳-碳和碳-氮键(例如，苯乙烯，二烯， 环丙烯)，具有高选择性和原子经济性。通过实验和理论研究，这 该项目将对各种过渡金属催化剂的机理产生基本的见解，包括Rh， 钴和铜。除了催化和机理研究之外，我们计划建立高活性的化学主题 对药物发现领域的重要意义。我们的目标是特权基序(例如，手性含氮化合物 杂环)和探索化学空间(例如，具有高SP3特性的三环笼子)。穿过 与其他领域的专家合作，我们解决了荧光显微镜、核磁共振等领域令人兴奋的挑战 光谱学，以及通过设计功能分子进行癌症免疫治疗。这个项目演示了 在催化、药物化学和生物学的界面上制造分子的创新。

Project Summary Research and training in organic synthesis impacts all fields of science that require the design and construction of molecular architecture. This project will advance catalytic methods, including hydroacylation and hydroamination, as attractive and powerful tools for chemical synthesis. The coupling methods proposed are modern and innovative because they rely on common functional groups (e.g., aldehydes, amines) to generate new carbon-carbon and carbon-nitrogen bonds from unsaturated partners (e.g., styrenes, dienes, cyclopropenes), with high selectivity and atom economy. Through experimental and theoretical studies, this project will yield fundamental insights into the mechanism of various transition metal catalysts, including rhodium, cobalt, and copper. Beyond catalysis and mechanistic studies, we plan to build chemical motifs of high significance to the field of drug discovery. We target privileged motifs (e.g., chiral nitrogen-containing heterocycles) and explore chemical space (e.g., tricyclic cages bearing high sp3 character). Through partnerships with experts in other fields, we address exciting challenges in fluorescent microscopy, NMR spectroscopy, and cancer immunotherapy by designing functional molecules. This project demonstrates innovation in making molecules at the interface of catalysis, medicinal chemistry, and biology.