"Organobismuth reagents in C-N, C-O, and C-C bond forming reactions and synthesis of biologically active compounds."

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The development of new methododologies that allow the efficient construction of C-O, C-N, and C-C bonds is essential in the preparation of pharmaceutically relevant compounds. The incorporation of functionalized small linear or cyclic alkyl groups on bioactive molecules facilitates the exploration of their binding environment and the fine tuning of interactions with the biological target. In addition, this exercise allows the optimization of the biophysical properties of the compounds, translating into improved pharmacokinetic profiles for the drug candidate. While many methods exist to perform such organic transformations, some of them suffer from poor substrate scope, require complex ligand/catalyst systems or necessitate reagents that are expensive and, in some cases, generate toxic side products. Organobismuth reagents have found wide applications in organic chemistry, in part due to their unique reactivity and the low cost and toxicity associated with bismuth salts. The current proposal focuses on the development of new synthetic methodologies that exploit the unique reactivity of organobismuth reagents in the transfer of highly functionalized alkyl groups onto privileged scaffolds used in medicinal chemistry, such as heterocycles, phenols, amides, and amines. Such methods should find broad applications in medicinal, process, or agricultural chemistry, by allowing the expedient synthesis of compounds which currently require multi-step sequences for their preparation. Students involved in this research program will learn state-of-the-art techniques as well as the related fundamental theory, preparing them for a successful career in industry or academia.