Cross-coupling, which relies on the use of transition metals, is among the most utilized chemical means of establishing carbon-carbon or carbon-heteteroatom bonds between appropriately functionalized sp, sp2, or sp3 centres. However, most cross-coupling reactions rely on the use of palladium to synthesize valuable synthetic targets. This is problematic for the chemical industry as palladium is limited in supply and expensive. Chemists have therefore sought to replace palladium with first-row transition metals (e.g., iron, cobalt and nickel) and recent reports on cobalt and nickel catalyzed cross-coupling reactions indicate that these metals can be used in this capacity. Unfortunately, protocols developed (so far) for these metals are unsuitable for the synthesis of targets with base-sensitive functional groups as they involve strongly basic reaction conditions.
Research in this thesis aims to develop both cobalt and nickel pre-formed catalysts that will display high catalytic activity in mildly basic reaction conditions. Current methodologies for cobalt and nickel cross-coupling reactions use either phosphine ligands or NHC ligands of moderate steric bulk (IMes or IPr). Recent advancements in the development of Pd-PEPPSI catalysts have demonstrated that both pre-forming the catalyst and using larger NHC ligands (IPent, IPentCl, or IHept) are required for high catalytic activity in weakly basic conditions. Thus, it was hypothesized that the development of pre-formed cobalt and nickel NHC complexes analogous to their Pd counterparts would improve reactivity in Negishi, Suzuki-Miyaura, and Buchwald-Hartwig amination cross-coupling reactions.
Co(IPent)Cl2(Pyr), Co(IPentCl)Cl2(Pyr), and Co2IPr2(OAc)4 were prepared, identified by X-ray crystallography, and evaluated in preliminary Negishi cross-coupling reactions. These complexes were found to be ineffective, but Co2IPr2(OAc)4 was found to be effective for Suzuki-Miyaura cross-coupling. A base screen was performed to enable the use of weak bases, however, the reaction only worked by pre-forming the boronate with n-BuLi, rendering the reaction conditions intolerant of base-sensitive functional groups.
[Ni(IPr)]2(µ-Cl)2 , Ni(IPr)Cl(allyl), and Ni(IPent)Cl(allyl) complexes were synthesized and evaluated in Buchwald-Hartwig aminations. Several bases were examined for these reactions but only sodium tert-butoxide was found to be effective. The presence of TEMPO and BHT in these transformations proved deleterious suggesting the involvement of radical intermediates. Finally, stoichiometric reactions were performed to isolate intermediates in the catalytic cycle, supporting the formation of nickel(0).
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/40722 |
| Date | 10 July 2020 |
| Creators | Lazarus, Michael Evan |
| Contributors | Organ, Michael |
| 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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