New Catalytic Technologies Impactful to Synthesis of Pharmaceuticals

University Of Missouri-Columbia, Columbia MO

Investigators

Abstract

. Modern pharmaceutical synthesis faces significant challenges in the production of complex, fluorinated, and highly functional molecules that are essential for ensuring the safety, potency, and stability of life-saving medications. This research program aims to address these challenges by developing safer and more efficient chemical methods that develop and leverage water-based reactions, cost-effective reagents, recyclable materials, and resource-efficient catalysts. The Handa Lab is set to lead innovations such as electromicellar catalysis in water, resource-efficient fluorination and trifluoromethylation of (hetero)aromatics, C-N cross-couplings of difficult molecules, and selective catalysis involving transient Pd(III) species, thereby enabling the synthesis of functionally enriched compounds, nitrogen-rich atropisomers, and other intricate drug components under mild conditions. Key research areas encompass: (1) electromicellar catalysis for the formation of fluorinated heterocycles, allenes, and reactive intermediates to access trifluoromethylated (hetero)aromatics using in situ derived reagents from safer sources; (2) enantioselective cross-couplings to access challenging atropisomers through the use of recyclable catalysts and in-house developed photoactive polymers that facilitate Dexter energy transfer; and (3) room-temperature cross-couplings of unreactive (hetero)aryl fluorides and chlorides, driven by surface-faceting or transient hot catalytic species, along with in situ regeneration of inactive catalysts to highly active forms. These strategies aim to enhance reaction selectivity, reduce costs, and improve safety, thereby making pharmaceutical manufacturing more efficient and accessible. Additionally, the program emphasizes the importance of training students in cutting-edge chemistry relevant to pharmaceuticals and fostering strong partnerships with the domestic pharmaceutical industry to translate discoveries into real-world health solutions.