Ruthenium-Catalyzed Enantioselective and Site-selective Functionalization of Carbon-Hydrogen Bonds and Their Applications in Target Synthesis - Project Summary The demand for novel synthetic chiral molecules in biomedical research and drug development is increasingly urgent. Chiral compounds and natural products play critical roles in biological and pharmaceutical applications. While direct conversion of C‒H bonds into functional groups presents new synthetic opportunities, achieving enantioselectivity for complex molecules remains a challenge. Recent advances in C–H activation have led to highly efficient catalytic systems, yet their widespread application in synthesizing complex organic building blocks, natural products, and pharmaceuticals remains underdeveloped. This research proposal aims to address these challenges through the development of ruthenium(II)-catalyzed enantioselective functionalization of arene and alkene derivatives, and their synthetic applications for asymmetric syntheses of natural products and structurally complex molecules. Readily accessible chiral catalysts and inexpensive ruthenium resources will be used for the development of practical catalytic systems and synthesis. Specifically, it targets the enantioselective functionalization of ortho- and meta-aryl C‒H bonds, leveraging a non-covalent interaction-based chiral induction model to enhance stereochemical control. Key objectives include the total synthesis of dendrofalconerol A and asymmetric synthesis of dinoxyline, utilizing enantioselective C‒H activation as a pivotal step. Additionally, the project aims to develop intermolecular enantioselective ortho- and meta-C–H functionalization of arenes, potentially yielding novel axially chiral indole-aryl compounds with applications in ligand design and pharmaceuticals. Furthermore, the research seeks to develop new enantioselective alkenyl C–H activation systems, exploring new hydrovinylation routes for generating unconventional products. This project offers undergraduate students at the University of North Texas hands-on experience in the cutting-edge field of C–H functionalization. By focusing on enantioselectivity in the catalytic processes and target molecule syntheses, students will deepen their understanding of chemical principles while gaining valuable skills for careers in biomedical, pharmaceutical, and health- related sciences. Engaging in Ru(II)-catalysis research, they will work at the intersection of catalysis, organic chemistry, and medicinal sciences, contributing to impactful discoveries and mastering the latest synthetic technologies. This experience will provide them with both technical expertise and the mindset needed to lead in the evolving landscape of pharmaceutical research.
