Dr. Jennifer S. Hirschi
Research Assistant Professor of Chemistry
- BS, Chemistry, Southern Utah University, Cedar City, UT, 2001
- PhD, Texas A&M University, College Station, TX, 2007
The asymmetric synthesis of organic molecules using chiral catalysts represents an important area in medicinal chemistry. Understanding the chiral space of such a catalyst and how it preferentially stabilizes the transition state environment of an enantioselective process is critical to reaction optimization, catalyst improvement, scale-up efforts and discovery of novel transformations. Theoretical studies involving density functional theory (DFT) methods provide in-silico insight into the geometry of the enantio-determining transition states of these reactions. A majority of such theoretical studies in the literature are reported several years after the initial discovery of the reaction leading to a rather sluggish translation of these technologies from an academic to an industrial setting. There is a critical need for interplay between physical organic studies and synthetic methodology development at the stage of new reaction discovery. My research program develops a concerted, iterative collaboration of these two important areas of organic chemistry to enable rapid maturation of new reaction methodology for applications in practical syntheses.
A second area of research emphasis involves the use of kinetic isotope effects as a probe of enzymatic transition structures. Knowledge of the transition structures of enzymatic reactions provides the electronic blueprint for inhibitor design. In collaboration with mechanistic enzymologists, my group uses DFT methods to develop a transition state model for enzymatic reactions that accurately predicts the experimentally determined kinetic isotope effect measurement.
Recent Selected Publications
Roytman, V. A.; Karugu, R. W.; Hong, Y.; Hirschi, J. S.; Vetticatt, M. J, 13C Kinetic Isotope Effects as a Quantitative Probe To Distinguish between Enol and Enamine Mechanisms in Aminocatalysis, 13C Kinetic Isotope Effects as a Quantitative Probe To Distinguish between Enol and Enamine Mechanisms in Aminocatalysis, Chem. Eur. J., 2018, 24, 8098-8102.
Gheewala, C.D.; Hirschi, J. S.; Lee, W-H.; Paley, D. W.; Vetticatt, M. J.; Lambert, T. H., Asymmetric Induction via a Helically Chiral Anion: Enantioselective Pentacarboxycyclopentadiene Brønsted Acid-Catalyzed Inverse-Electron-Demand Diels–Alder Cycloaddition of Oxocarbenium Ions, J. Am. Chem. Soc., 2018, 140, 3523-3527.
Gu, H.; Chio, T. I.; Lei, Z.; Staples, R. J.; Hirschi, J. S.; Bane, S., Formation of hydrazones and stabilized boron–nitrogen heterocycles in aqueous solution from carbohydrazides and ortho-formylphenylboronic acids, Org. Biomol. Chem., 2017, 15, 7543-7548.