The purpose of this study was to develop new routes to couple commercially and/or readily available starting materials into biologically relevant structures via one-pot transition metal catalyzed multicomponent coupling reactions. More specifically, we showed that a palladium catalyst could couple imines, acid chlorides and carbon monoxide to directly generate 1,3-oxazolium-5-oxides (Munchnones). / Chapter 2 of this thesis describes a new palladium catalyzed multicomponent synthesis of beta-lactams. This reaction was developed based upon previous work in this laboratory, which showed that imidazoline-carboxylates could be generated from coupling two imines, an acid chloride and CO. Mechanistic studies suggested that this product arose from a 1,3-dipolar cycloaddition of an imine-HCl molecule with Munchnone. Removal of this acid combined with adjusting reactant ratios, and the utilization of ligands generated 3-amido substituted beta-lactams in moderate to good yields. / Chapter 3 discusses studies that further explain the origin of the beta-lactam and imidazoline-carboxylate products obtained from catalysis. These studies demonstrate that imidazoline-carboxylates are generated either directly through a 1,3-dipolar cycloaddition reaction of imine-HCl with Munchnone, or indirectly from acid catalyzed rearrangement of an initially formed beta-lactam. In addition, the potential intermediates in the catalytic cycle, including the palladium bound carbonyl complex are completely characterized. / Chapter 4 describes the first example of a metal-catalyzed synthesis of Munchnones. Reaction optimization focused on modifying the catalyst structure to {Pd(Cl)[eta2-CH(R1)NR 2COR3]}2 (formed by pre-treating Pd 2(dba)3 CHCl3 with imine (R1C(H) = NR2) and acid chloride (R3COCl)), increasing CO pressures and employing bromide salts to stabilize the palladium catalyst. These modifications to the reaction enabled the development of a catalytic Munchnone synthesis from imines, acid chlorides, and CO. / Chapter 5 describes the development of a highly modular one-step palladium catalyzed synthesis of pyrroles. This reaction shows that pyrroles can be thought of as being a coupling product of an imine, acid chloride and an alkyne, formed via the in situ trapping of Munchnones with alkynes. In addition, further improvements to the Munchnone synthesis through the utilization of sterically bulky phosphine ligands (i.e. [P(o-Tol) 3]) will be discussed. As well as broadening the scope of accessible Munchnones, this ligand also increased the rate of product formation. / Chapter 6 describes some preliminary studies on the mechanism of Munchnone synthesis. Based upon kinetic data and catalyst resting state analyses, the rate determining step was suggested to possibly be N-acyliminium salt oxidative addition to Pd(0). In addition, crystal structures of {[P( o-Tol)3]Pd(eta2-CH(Tol)N(PMB)COPh)} and its dimeric precursor {Pd(eta2-CH(Tol)N(PMB)COPh)}2 were obtained.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.85065 |
| Date | January 2004 |
| Creators | Dhawan, Rajiv |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 002173832, proquestno: AAINR06291, Theses scanned by UMI/ProQuest. |
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