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Topic

Mechanistic Investigations of Palladium-Catalyzed Cross-Coupling Reactions Using Advanced Mass Spectrometric Methodologies

Department of Chemistry

Date & location

• Wednesday, April 16, 2025
• 8:30 A.M.
• Elliott Building, Room 230

Examining Committee

Supervisory Committee

• Dr. Scott McIndoe, Department of Chemistry, University of Victoria (Supervisor)
• Dr. David Leitch, Department of Chemistry, UVic (Member)
• Dr. Alisdair Boraston, Department of Biochemistry and Microbiology, UVic (Outside Member)

External Examiner

• Dr. Jason Hein, Department of Chemistry, University of British Columbia

Chair of Oral Examination

• Dr. Cindy Holder, Department of Philosophy, UVic

Abstract

This dissertation explores the application of mass spectrometry (MS) as a tool for investigating the mechanisms of palladium-catalyzed cross-coupling (PdCC) reactions. By integrating advanced MS techniques with reaction monitoring methodologies, this work provides insights into catalytic activation processes, the role of intermediates, and the limitations of MS in analyzing complex chemical systems. The research is presented across five chapters, each examining specific aspects of MS in the context of organometallic catalysis.

The first chapter establishes the foundational context, detailing the principles of MS and its role in studying PdCC reactions. A particular focus is placed on electrospray ionization mass spectrometry (ESI-MS) and pressurized sample infusion (PSI), highlighting their advantages and challenges in capturing transient catalytic species. Chapter 2 discusses the inherent limitations of MS in characterizing high molecular weight polymers, a common product of PdCC reactions. Factors such as diminishing signal-to-noise (S/N) ratios, isotope pattern broadening, and ionization inefficiencies are examined, and strategies for improving polymer analysis via MS are proposed.

Chapter 3 evaluates the performance of ESI-MS across different instruments, particularly in detecting fragile organometallic complexes. A multi-instrument comparative study reveals significant variability in instrument performance, emphasizing the necessity for optimizing instrument parameters to preserve weakly bound catalytic species. Chapter 4 critically re-examines the mercury drop test, a widely used method for distinguishing between homogeneous and heterogeneous catalysis. This analysis demonstrates that mercury interacts with Pd intermediates through redox-transmetallation and amalgamation processes, leading to potential misinterpretations of catalytic activity.

Finally, Chapter 5 investigates a new-generation palladium precatalyst, (^DMPDAB)Pd(CH₂SiMe₃)₂, providing mechanistic insights into ligand substitution, catalyst activation, and oxidative addition processes. The combination of PSI-ESI-MS and real-time monitoring enabled the identification of key catalytic intermediates, contributing to the development of more efficient and selective Pd-based catalysts. Collectively, this dissertation advances the understanding of MS as a tool for elucidating catalytic processes, offering methodological improvements and new perspectives on PdCC reaction mechanisms. The findings have broad implications for catalyst design, sustainability, and the continued evolution of mass spectrometric techniques in organometallic chemistry.