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Development of practical in-situ methods for the early transition metal-catalyzed synthesis of amines

University of British Columbia

The research presented in this thesis focuses on the development of practical methods for the early transition metal-catalyzed synthesis of amines. The primary focus of this thesis is the development of in-situ generated tantalum catalyst systems for the intermolecular hydroaminoalkylation of alkenes with amines. The intramolecular hydroamination of aminoalkynes followed by asymmetric transfer hydrogenation for the synthesis of chiral 1,4-benzoxazines was also developed. The substrate scope and synthetic utility of these reactions is presented herein. Initial efforts to expand the synthetic utility of hydroaminoalkylation focused on the use of a previously reported phosphoramidate tantalum methyl complex as a catalyst for the hydroaminoalkylation of norbornadiene to produce amine-containing monomers. The optimization of this reaction demonstrated key challenges in the use of hydroaminoalkylation as a synthetic tool. To address these challenges, methods for the in-situ generation of hydroaminoalkylation catalysts were developed. The generation of a pyridonate tantalum dimethylamido catalyst in-situ allowed for a robust catalyst that exhibited an unprecedented substrate scope. Attempts to further probe the reaction through modifying the electronic properties of the pyridonate ligand were unsuccessful. Products accessible from this catalyst system were further reacted to generate poly-methylated piperidines that would be difficult to synthesize through traditional methods. A second in-situ method utilizes tantalum pentafluoride, which is more robust than previously utilized tantalum precursors, to generate a hydroaminoalkylation catalyst in-situ. The substrate scope of this system was explored, and further reactions allowed for the synthesis of 1,2,3,4-tetrahydroquinolines. The generation of this catalyst was studied through NMR spectroscopy. The stability of tantalum pentafluoride towards storage in ambient conditions was also studied, showing that while it could not be stored in a non-inert atmosphere, it could be handled in ambient conditions without significant loss of reactivity. Chiral 1,4-benzoxazines are an important class of compounds that form the core of many industrially relevant compounds. By utilizing a previously reported method for the asymmetric synthesis of morpholines through sequential hydroamination/asymmetric transfer hydrogenation, a variety of chiral 1,4-benzoxazines can be synthesized from readily accessible 2-aminophenyl propargyl ethers. While the synthesis suffers from poor yields, the method achieves moderate to good enantiomeric excesses and demonstrates improved step-efficiency.

Text

2020-01-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/68314

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/