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Topic

Palladium-Catalyzed Carboxylate C–O Bond Activation

Department of Chemistry

Date & location

• Monday, December 16, 2024
• 11:00 A.M.
• Elliott Building, Room 228

Examining Committee

Supervisory Committee

• Dr. David Leitch, Department of Chemistry, University of Victoria (Supervisor)
• Dr. Scott McIndoe, Department of Chemistry, UVic (Member)
• Dr. Heather Buckley, Department of Chemistry, UVic (Member)
• Dr. Jay Cullen, School of Earth and Ocean Sciences, UVic (Outside Member)

External Examiner

• Dr. Timothy Brewster, Department of Chemistry, University of Memphis

Chair of Oral Examination

• Dr. Michael McGuire, Department of Electrical and Computer Engineering, UVic

Abstract

Carboxylate C–O bonds are atom-economical, robust in synthesis, and easily accessible, but have traditionally been ineffective synthetic handles for Pd catalysis. In this thesis the utility of these cross-coupling handles in Pd catalysis has been established. As global climate issues necessitate an alternative to oil-based processes, the development of Pd-catalyzed C–O bond activation chemistry, such as the chemistry explored in this thesis, has the potential to aid in biomass becoming a common future feedstock.

This thesis is divided into three research chapters. Firstly, we evaluated the mechanism of an open to air, base-free, Pd-catalyzed cross coupling of enol carboxylates and aryl boronic acids that was first developed within the Leitch Lab. This experimental evaluation uncovered key intermediates that allowed us to propose a cationic Pd(II)-only mechanism. Secondly, the knowledge gained in evaluating the mechanism was applied to Miyaura borylation of various enol carboxylates. In this study we uncovered that the nature of the enol carboxylate and the boron source greatly impacted the reactivity in the initial synthesis as well as any future desired reactivity of the enol boronate. Finally, by identifying active pharmaceutical ingredients, specifically pyrido[1,2-a]pyrimidin-4-ones, that could be used in future C–O activation chemistry, we systematically approached their synthesis to create and characterize a library of substituted molecules. We then demonstrated that we could functionalize these molecules with both pivalate and tosylate synthetic handles. Because the fundamental reactivity of these carboxylate C–O is established, these three chapters have created myriad potential research projects.