Date of Award
Summer 2023
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Yi, Chae S.
Second Advisor
Donaldson, William A.
Third Advisor
Fiedler, Adam
Abstract
Transition metal catalyzed selective C–C and C–N bond activation reactions emerged as an effective synthetic tool in organic chemistry. Reorganization of these bond connections allows access to complex molecular scaffolds from readily available starting materials which are immensely useful for organic synthesis of pharmaceutical agents. While enormous progress has been achieved to date, major challenges still remain in desigining broad applicable catalytic bond activation methods. The well-defined cationic Ru–H complex with a benzoquinone ligand was found to be an effective catalytic system for the deaminative coupling reaction of enones with amines which enable regioselective cleavage of unstrained Cα–Cβ bond of enones. The analogous catalytic coupling reaction of enones with anilines produced a mixture of N-alkylanilines and 2,4-disubstituted quinoline/es via Cα-Cβ bond cleavage of enones. The combined experimental and DFT calculations uncovered a mechanism of the coupling reaction via the formation of β-aminoimine substrate and a series of Ru-catalyzed C–C cleavage and C–N cleavage processes followed by hydrolysis and hydrogenation of the resulting imines. The cationic Ru–H complex was also found to be an effective catalyst for the hydrodeaminative coupling reactions of phenols with nitriles, which involves C–N cleavage of nitriles in forming 2-alkylphenol products. The inverted V-shaped Hammett plot revealed a change in rate-limiting step which is influenced by the electronic nature of nitrile substrates. A plausible mechanism of the reaction has been proposed on the basis of experiemtnal results, which proceeds via hydrogenation of nitriles followed by nucleophilic coupling and hydrogenolysis steps.