Design of Bidentate Chiral Nitrogen-Ligands for Asymmetric Catalysis

About This Grant

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Diao of New York University is studying new ways to make medicines more efficiently and in a way that is better for the environment. Many medicines are made from small molecules whose 3D configurations are very important—they affect how well the medicine works and how long it stays in the body. Right now, most of these molecules are made using the conventional methods that create a lot of extra waste. A newer approach, called asymmetric catalysis, could make these medicines faster and with less waste, but it is limited by the availability of special tools called "chiral ligands." This project will focus on creating new chiral ligands that work with earth-abundant metals to make the process cleaner and more efficient. This research will also give students valuable experience in solving scientific problems, working in teams, and understanding how their work can help society. In addition, the project will include outreach activities like working with the New York Public Library to lead hands-on science experiments for children and creating a chemistry-themed video game to inspire interest in science, technology, engineering, and math (STEM). These efforts will help spark curiosity and encourage the next generation of scientists. With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Diao of New York University is studying new chiral nitrogen ligands to facilitate asymmetric base metal catalysis. Bidentate nitrogen ligands are effective in base metal catalysis for their strong coordination and redox activity, yet chiral nitrogen ligands remain limited. To address this challenge, this project will develop novel C1-symmetric bidentate nitrogen ligands—Imine-Oxazoline (ImOx) and Imine-Imidazole (ImIm)—derived from amino acids. The low symmetry of these ligands will enable independent optimization at each coordination site to enhance catalytic performance. Preliminary studies have established the synthesis of ImOx and demonstrated its ability to improve the enantioselectivity of palladium-catalyzed conjugate additions, showing a strong correlation between enantiomeric excess and steric effects at both donor sites. Building on these findings, research in this project will expand the ImOx ligand library, synthesize ImIm analogs, and apply these ligands in nickel-catalyzed asymmetric reductive conjugate addition reactions. The resulting pharmaceutically relevant products will support drug discovery efforts. Complementary organometallic studies will elucidate the structural and redox properties of ImOx, ImIm, and their metal complexes, thereby advancing ligand design principles for asymmetric catalysis. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.