With this CAREER award, the Chemical Synthesis Program of the NSF Chemistry Division supports the research of Professor Andrew McNally in the Department of Chemistry at Colorado State University. Professor McNally and his students develop new synthetic methods that allow common building blocks of pharmaceuticals and agrochemicals to be transformed into biologically active derivatives. In particular, pyridines are among the most widely encountered structures in current drug compounds. Research in Professor McNally's laboratory exploits the unique reactivity of new bond-forming reactions on pyridines, to make complex pharmaceuticals. This project is a combination of organic synthesis, medicinal chemistry and catalysis that is preparing his students for careers at the forefront of the chemical sciences. Educational activities focus on increasing enrollment into undergraduate programs, preparing graduate students for the pharmaceutical industry via a new medicinal chemistry program and changing the public's perception of chemistry in society through a new series of 'pub lectures'.
Pyridines are used widely across the chemical sciences including applications as pharmaceuticals, agrochemicals, materials and ligands. Despite their importance, there are deficiencies in the current synthetic toolkit to prepare valuable pyridine derivatives. This project develops new chemical transformation of pyridines using phosphorus compounds as reagents and catalysts. Three distinct questions are addressed in this project: 1) Can phosphonium salts be formed on complex polypyridines with 'switchable' control of site-selectivity? Can phosphorus ligand-coupling reactions be used to enable sp2-sp3 coupling in new pyridine alkylation reactions? 3) Can phosphorus intermediates, and new catalytic approaches, enable 3-position selective halogenation, trifluoromethylation and amination reactions? The educational plan focuses on increasing the enrollment in the undergraduate chemistry program through a chemistry in context lecture series. At the graduate level, students are enrolling in a new medicinal chemistry course that includes guest lectures from medicinal chemists. The public is engaged through a new 'pub lecture' series that tackles contemporary and controversial aspects of chemistry in society.
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.
