Nahiane Pipaon Fernández

Topic

High-Throughput Compatible Catalyst Development Towards Sustainable Direct Alkenylation Reaction Discovery and Optimization

Department of Chemistry

Date & location

• Monday, August 19, 2024
• 11:00 A.M.
• Elliott Building, Room 228

Examining Committee

Supervisory Committee

• Dr. David Leitch, Department of Chemistry, University of Victoria (Supervisor)
• Dr. Cornelia Bohne, Department of Chemistry, UVic (Member)
• Dr. Lisa Rosenberg, Department of Chemistry, UVic (Member)
• Dr. John Burke, Department of Biochemistry and Microbiology, UVic (Outside Member)

External Examiner

• Dr. Jeffrey Van Humbeck, Department of Chemistry, University of Calgary

Chair of Oral Examination

• Dr. Kathryn Jackson, Department of Physics and Astronomy, UVic

Abstract

The direct C–H functionalization of heteroaromatic compounds such as pyridine, furan, thiophenes, thiazoles, and others have been developed as effective methods for making Csp²–Csp² linkages which are often found in biologically active compounds and π-conjugated functional materials. More specifically, the development of palladium catalysts that can selectively activate specific C–H bonds is key for late-stage functionalization of pharmaceutically-relevant compounds. Mechanistic studies of the catalytic system, reaction intermediates and evaluation of the reaction parameters allows chemists maximize the reaction performance.

This thesis explores direct C–H alkenylation reactions from both a catalyst and substrate perspective, and exploits modifications to the generally accepted direct alkenylation mechanism. Furthermore, this work shows how systematic, hypothesis-driven High-Throughput Experimentation of reaction conditions, palladium sources and ancillary ligands enables the development of new reactivity, optimization of catalytic systems and exploration of the chemical space of direct alkenylation of heterocycles.

Finally, this work also highlights the versatility of palladacyclic precatalysts in the selective C–H functionalization of challenging but pharmaceutically relevant heterocycles such as pyrazoles and thiazoles. New synthetic procedures have been described toward the development of single-component precatalyst systems, and they have been used for the synthesis of two pharmaceutical compounds: GSK3368715, a PRMT1 inhibitor, and fatostatin, a lipid accumulation inhibitor.