Towards Absolute Asymmetric Synthesis

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This award from the Chemical Synthesis Program of the Chemistry Division goes to support research by Professor Tehshik Yoon of the University of Wisconsin-Madison's Chemistry Department. Professor Yoon is interested in the "chirality", or "handedness", of small organic molecules. Many important organic molecules, including drug molecules and biologically important molecules like amino acids and sugars can exist in either left- or right-handed forms, with only one form being biologically desirable. The undesirable form can be harmful, so almost all new drug-candidates or diagnostic probes must be of only one "handedness". Light can also be produced with either left- or right-handed circular polarizations. The long-term goal of this project is to use the handedness of circularly polarized light to dictate the handedness of a small organic molecule. This is accomplished by designing helically chiral catalysts that can first be selectively activated by circularly polarized light with only one handedness and then transferring that handedness to a chemical reaction and its resultant product. This project requires an interdisciplinary approach that combines synthetic organic chemistry, organometallic chemistry, photochemistry, and computational chemistry to achieve its objectives, and in that way it provides outstanding training for students. Professor Yoon is also a leader in efforts to increase the diversity of students who undertake careers in science, and the project includes broader impacts that continue these important efforts. The chiral photocatalysts studied in this project are octahedral iridium complexes whose ligands are arranged about the metal with well-defined helical chirality. This class of compounds constitutes an attractive starting point for these studies because they possess a robust and well-studied photochemistry, because they have been recently shown to be quite effective photosensitizers for a range of organic transformations, and because they can easily be synthesized in stereochemically pure form. The first phase of this project shows that the chirality of a single enantiomer of a helically chiral iridium photocatalyst can be transmitted to a newly formed organic photocycloadduct. The second phase seeks understanding of the structure-activity relationships necessary for effective enantioselective photocatalysis. The third and most ambitious phase attempts to identify orthogonal structural features that enable selective activation of a racemic mixture of chiral Ir photocatalysts with circularly polarized light. The broader impacts of this project train a diverse set of graduate, undergraduate, and postdoctoral researchers in cutting-edge synthetic organic chemistry relevant to the construction of potential new drugs, materials, and fine chemicals.