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Early transition metal complexes of pyridine derivatives : applications in the catalytic synthesis of amines and N-heterocycles Chong, Eugene
Abstract
The work described in this thesis focuses on the development of pyridine-derived group 4 and 5 complexes for application in the catalytic synthesis of selectively substituted amines. Two different catalytic alkene hydrofunctionalization reactions were targeted: hydroamination and hydroaminoalkylation. Respectively, these transformations provide atom-economical strategies for the formation of new C–N and C–C bonds on amines, using simple alkenes as the alkylating agents. A series of bulky mono(2-aminopyridinate)tris(dimethylamido)titanium complexes with varying steric parameters were synthesized and explored for intramolecular hydroamination reactivity using aminoalkene substrates. A titanium catalyst capable of room-temperature hydroamination reactivity was identified for the synthesis of gem-disubstituted 5- and 6-membered-ring products. This catalyst has good breadth of reactivity, including the challenging 7-membered-azepane ring formation and hydroamination with internal alkenes. A catalytically active 2-aminopyridnate-supported imido titanium complex was prepared, and reactivity investigations of this complex suggest that this reaction proceeds via an intermediate imido [2+2] cycloaddition pathway. Various 3-substituted-2-pyridonate ligands were synthesized and examined as ancillary ligands for targeting chemoselectivity for intramolecular hydroaminoalkylation over hydroamination. Systematic ligand screening studies showed that bis(3-phenyl-2-pyridonate)bis(dimethylamido)titanium complex is selective for hydroaminoalkylation over hydroamination. This is the first catalyst that can selectively α-alkylate primary aminoalkenes to access both 5- and 6-membered-cycloalkylamines with good substrate-dependent diastereoselectivity. Mechanistic and stoichiometric experiments using this complex support the involvement of a bimetallic imido species in the reaction. Notably, a titanium(III) species was isolated during these investigations. Reliable synthesis of this titanium(III) complex and examination of its reactivity showed that it is not active for hydroaminoalkylation. Varying combinations of mixed 2-pyridonate/alkyl/amido/chloro tantalum complexes were targeted to expand the substrate scope for intermolecular hydroaminoalkylation. The synthesis of mono(2-pyridonate)/alkyl/chloro tantalum complex was unsuccessful. Instead, bis(2-pyridonate)tantalum alkyl complexes were formed. While these complexes showed hydroaminoalkylation reactivity for terminal alkenes, their thermal and light sensitivity presents difficulty for synthetic application. The design and synthesis of a mixed 2-pyridonate-Ta(NMe₂)₃Cl provided a sterically accessible metal center for the hydroaminoalkylation of sterically demanding disubstituted alkenes. This complex is the first effective precatalyst for the alpha-alkylation of unprotected secondary amines using unactivated (E)- and (Z)-internal alkenes without C=C bond isomerization.
Item Metadata
Title |
Early transition metal complexes of pyridine derivatives : applications in the catalytic synthesis of amines and N-heterocycles
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2014
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Description |
The work described in this thesis focuses on the development of pyridine-derived group 4 and 5 complexes for application in the catalytic synthesis of selectively substituted amines. Two different catalytic alkene hydrofunctionalization reactions were targeted: hydroamination and hydroaminoalkylation. Respectively, these transformations provide atom-economical strategies for the formation of new C–N and C–C bonds on amines, using simple alkenes as the alkylating agents. A series of bulky mono(2-aminopyridinate)tris(dimethylamido)titanium complexes with varying steric parameters were synthesized and explored for intramolecular hydroamination reactivity using aminoalkene substrates. A titanium catalyst capable of room-temperature hydroamination reactivity was identified for the synthesis of gem-disubstituted 5- and 6-membered-ring products. This catalyst has good breadth of reactivity, including the challenging 7-membered-azepane ring formation and hydroamination with internal alkenes. A catalytically active 2-aminopyridnate-supported imido titanium complex was prepared, and reactivity investigations of this complex suggest that this reaction proceeds via an intermediate imido [2+2] cycloaddition pathway. Various 3-substituted-2-pyridonate ligands were synthesized and examined as ancillary ligands for targeting chemoselectivity for intramolecular hydroaminoalkylation over hydroamination. Systematic ligand screening studies showed that bis(3-phenyl-2-pyridonate)bis(dimethylamido)titanium complex is selective for hydroaminoalkylation over hydroamination. This is the first catalyst that can selectively α-alkylate primary aminoalkenes to access both 5- and 6-membered-cycloalkylamines with good substrate-dependent diastereoselectivity. Mechanistic and stoichiometric experiments using this complex support the involvement of a bimetallic imido species in the reaction. Notably, a titanium(III) species was isolated during these investigations. Reliable synthesis of this titanium(III) complex and examination of its reactivity showed that it is not active for hydroaminoalkylation. Varying combinations of mixed 2-pyridonate/alkyl/amido/chloro tantalum complexes were targeted to expand the substrate scope for intermolecular hydroaminoalkylation. The synthesis of mono(2-pyridonate)/alkyl/chloro tantalum complex was unsuccessful. Instead, bis(2-pyridonate)tantalum alkyl complexes were formed. While these complexes showed hydroaminoalkylation reactivity for terminal alkenes, their thermal and light sensitivity presents difficulty for synthetic application. The design and synthesis of a mixed 2-pyridonate-Ta(NMe₂)₃Cl provided a sterically accessible metal center for the hydroaminoalkylation of sterically demanding disubstituted alkenes. This complex is the first effective precatalyst for the alpha-alkylation of unprotected secondary amines using unactivated (E)- and (Z)-internal alkenes without C=C bond isomerization.
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Genre | |
Type | |
Language |
eng
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Date Available |
2014-11-07
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivs 2.5 Canada
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DOI |
10.14288/1.0167040
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2015-02
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivs 2.5 Canada