The development of non-amino acid routes for the construction of peptides remains a challenge. The main goal of this study is to develop a new transition metal-mediated route to synthesize alpha-amino acid and peptide derivatives from imines and carbon monoxide. The proposed approach requires the sequential insertion of CO and imine into late transition metal sigma-bonds. / In Chapters 2 and 3, the ability of the palladium complex L2Pd(CH 3)N(R)=C(H)R'+ X- [L2 = chelating nitrogen ligands, X- = non-coordinating counteranion] to mediate the insertion of imines is examined. While L 2Pd(CH3)N(R)=C(H)R'+ X- is inert towards imine insertion into a palladium-methyl bond, the addition of CO to L2Pd(CH3)N(R)=C(H)R '+ X- yields the palladium-acyl complex L2Pd(COCH3)N(R)=C(H)R' +X-, which subsequently reacts to form the novel product of imine insertion: (L2)Pd[eta2-CH(R ')NRCOCH3]+X-. This demonstrates that these palladium complexes can undergo the novel sequential insertion of carbon monoxide and imine into the palladium-carbon bond in a manner directly analogous to that observed in olefin/CO alternating co-polymerizations. Examination of the mechanism of imine insertion (Chapter 3) demonstrates that, unlike olefins, imines undergo a concerted migration from the sigma-imine complex to form the product of imine insertion. The X-ray structure of the insertion complex 2.6b suggests the unique combination of amide bond formation, carbonyl oxygen chelation, and resonance stabilization of the chelate ring provides the stabilization required for this reaction to occur. / The product of CO/imine insertion is found to be inert towards reaction with carbon monoxide (Chapter 4). However, the addition of CO to its chloride analogue, generated via the oxidative addition of N-acyl iminium salts Tol(H)C=N(CH 2Ph)COPh+Cl- to Pd2(dba) 3•CHCl3 in the presence of 2,2'-bipyridine, results in the formation of 2-imidazolinecarboxylate derivatives (Chapter 5). Mechanistic studies reveal that imidazoline formation occurs via CO insertion into Pd--C bond of (bipy)Pd[eta2-CH(R' )NRCOR″]+Cl-, generating a palladium-bound alpha-amino acid derivative, which is followed by coupling with imine. This reaction is extended into a novel one pot palladium-catalyzed coupling of imine, carbon monoxide and acid chloride into 2-imidazolinecarboxylate derivatives. The described methodology provides a facile route to access the biologically relevant imidazoline derivatives through the sequential insertion of CO and imine into palladium-alkyl bonds.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.36803 |
| Date | January 2000 |
| Creators | Dghaym, Rania. |
| Contributors | Arndtsen, Bruce (advisor) |
| 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: 001780317, proquestno: NQ69867, Theses scanned by UMI/ProQuest. |
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