Date of Award

1-2023

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Chemistry and Biochemistry

Thesis Sponsor/Dissertation Chair/Project Chair

Henk Eshuis

Committee Member

Saliya Desilva

Committee Member

Mark Whitener

Abstract

This work is a computational study of a reaction mechanism for the trifluoromethylation of boronic acids. Three steps of the proposed reaction mechanism are studied, •CF3 addition to a copper catalyst center, base promoted transmetalation between copper and aryl boronic acid, and bond forming reductive elimination in which the CF3 and aryl substituent form a bond. Limited information is known about this mechanism. This study uses computational methods to attempt to elucidate the mechanism and provide the groundwork for potential improvement. Quantum chemical methods in conjunction with tight-binding based conformational sampling methods are used to investigate the possible pathways, their intermediates, and their transition states. Reaction energy pathways were successfully calculated for each step in the proposed mechanism. Transition states were found in the second and third steps, and the pathway appeared to be thermodynamically reasonable. A second proposed reaction mechanism, in which the base promoted transmetalation occurs before the •CF3 addition, was found to be thermodynamically unfavorable when compared to the original proposed mechanism, in which the •CF3 addition happens first. These calculations were benchmarked using multiple density functionals as well as the Random Phase Approximation and Møller-Plesset Perturbation methods. Free energy calculations showed relatively low, around 2 kcal/mol, thermal effects on the reaction energies. Solvent analysis using an implicit solvent model was ineffective, but explicit solvent calculations showed a significant decrease in reaction energies when the solvent is included. This implies that explicit solvent inclusion is necessary for future investigation of this mechanism. These results serve as a preliminary computational investigation into this reaction mechanism, and provide useful information for future attempts to optimize trifluoromethylation reactions.

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