Olefin metathesis is an outstandingly versatile methodology for the catalytic assembly of carbon-carbon bonds. Metathesis methodologies have been widely embraced since the advent of easily-handled ruthenium catalysts. However, industrial implementation has lagged. Problems of reliability and productivity arising from catalyst decomposition have impeded broad uptake of metathesis in process chemistry. Such challenges also hamper deployment of metathesis in forefront applications such as chemical biology. Better understanding of the mechanisms by which catalysts decompose can thus improve performance in demanding applications, as well as providing guidelines for informed process and catalyst design. Oxygen is often viewed as a relatively innocuous contaminant in reactions promoted by these late transition metal catalysts. Indeed, multiple reports comment on the desirability and operational simplicity of metathesis in air. We suspected, however, that deleterious impacts of O2 may be masked by the high catalyst loadings typically deployed in such reports. The first part of this thesis focuses on examining the robustness of leading metathesis catalysts toward oxygen. Systems examined include the classic, dominant N-heterocyclic carbene (NHC) derivatives, as well as recent breakthrough analogues containing cyclic alkyl amino carbene (CAAC) ligands. Both are shown to be decomposed by oxygen, but the CAAC catalysts are found to be not only more productive, but significantly more O2-tolerant. This is important as it overturns the widespread belief that high catalyst activity is invariably a trade-off against higher sensitivity. Studies of the initial oxidation event for the second-generation Grubbs catalyst RuCl2(H2IMes)(PCy3)(=CHPh) suggest that [2+2] cycloaddition of O2, as well as bimolecular decomposition of the four- coordinate species generated by PCy3 oxidation, account for ca. 90% of the observed decomposition. A previously-proposed pathway involving attack of O2 at the benzylidene ligand appears to be a minor contributor. In Chapter 3 of this thesis, a new strategy for inhibiting catalyst decomposition is examined. Specifically, cationic metathesis catalysts were encapsulated within a supramolecular resorcinarene capsule, which self-assembles around the catalysts in water-saturated toluene. Encapsulation nearly doubles RCM yields relative to the parent, neutral catalyst in water-saturated toluene. The increased catalyst productivity is enabled by site-isolation of the catalyst within the capsule, which prevents bimolecular decomposition, and by the hydrophobic nature of the capsule interior, which limits decomposition by water. A final study focuses on attempts to identify a more robust catalyst via ligand redesign. Examined for this purpose are recently reported, electron-rich pyridinylide aminophosphines (PyAPs; these take the general form R2P–N=Ar), which exhibit enhanced s-donor properties relative to NHCs. Strategies for incorporation of PyAP ligands into Ru metathesis catalysts are developed, and the catalytic activity of these species is described. PyAP catalysts are found be significantly less active than the corresponding NHC catalysts, despite their higher donicity. Poor performance results from facile catalyst decomposition. Where the N=Ar group lacks substituents at the ortho sites, o- metalation enables decomposition of the precatalyst. More problematically, the nitrogen atom appears to participate in nucleophilic attack on the key, metathesis-enabling [Ru]=CHR functionality, limiting the potential use of this class of phosphine in metathesis. Criteria for the development of more robust second-generation phosphine catalysts are proposed.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/40723 |
| Date | 13 July 2020 |
| Creators | Ton, Stephanie Jean |
| Contributors | Fogg, Deryn |
| Publisher | Université d'Ottawa / University of Ottawa |
| Source Sets | Université d’Ottawa |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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