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Sequential intermolecular hydroamination of alkynes and amines towards the synthesis of nitrogen-containing compounds

University of British Columbia

This thesis details the development of sequential intermolecular hydroamination of alkynes with amines followed by other reactions for the synthesis nitrogen-containing compounds, such as amines and heterocycles. The main feature of this thesis is the use of a bis(amidate)bis(amido)titanium complex, also known as the Schafer titanium catalyst, for the catalytic intermolecular hydroamination of terminal and internal alkynes. The catalytic synthesis of linear secondary amines using the Schafer titanium catalyst was accomplished through an intermolecular hydroamination of terminal alkynes followed by a Pd/C hydrogenation. The clean formation of products allowed for a facile synthesis and isolation of 23 examples of secondary amines in yields of 33-99%. The developed methodology allows for the synthesis of a variety of secondary amines containing aryl or alkyl substituents within a few hours and without the need for column chromatography. The selective anti-Markovnikov hydroamination of alkynes and ammonia remains a challenge. The first example of a hydroamination reaction with N-silylamine as an ammonia surrogate is disclosed in this thesis. Synthesis of anhydrous N-silylamine was accomplished using gaseous ammonia and tert-butyldimethylchlorosilane, which was then reacted with a variety of terminal and internal alkynes, leading to the synthesis of 25 examples of N- silylenamines in yields of 54-99%. The synthesis of primary amines (9 examples) was also accomplished upon treatment of the reaction mixture with palladium on carbon (Pd/C) and H₂. The isolation and characterization of key organometallic titanium-imido complexes was performed to probe the mechanism of the hydroamination reaction. Computational studies were also performed to study the preference of the N-silylenamine over the N-silylimine tautomer. Upon the remark that N-silylenamines were observed exclusively in the majority of cases, it was reasoned that such synthons could be used towards the synthesis of pyridines. Following the reported hydroamination reaction, a large variety of pyridines were formed with the addition of α,β-unsaturated followed by an oxidation event. This methodology allowed for the synthesis of 47 examples of mono-, di-, tri-, tetra-, and penta-substituted pyridines in yields of 11-96%.

Text

2019-10-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/67626

Chemistry

University of British Columbia

UBCV

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