The prevalence of fluorine in natural products is scarce. There are but a handful of compounds that have been discovered to date. This could be largely attributable to the occurrence of fluorine in nature as fluoride (F-). — One might recognize such nomenclature from the ingredients list on a toothpaste tube — In fact, naturally occurring fluoride is most commonly found as fluorite (CaF2) or cryolite (Na3AlF6). As such, the introduction of fluorine via biological pathways has been limited to use of aqueous F- (a very poor nucleophile). This fact — coupled with its naturally low concentration in water — has created the ripe conditions for this shortage. In a way this has proven fertile for synthetic chemists because nature has not yet evolved a method for the deconstruction of partially or fully fluorinated compounds.
Considering the above, as synthetic methodologies for the construction of carbon-fluorine bonds became available, so too did the discovery of their valuable properties. So beneficial are these properties that C-F bond-containing compounds have become commonplace in many households throughout the world. For example, practically every home relies on these compounds for use in their refrigerators. Other examples of useful fluorinated materials include blowing agents, non-stick coatings, pharmaceuticals, agrochemicals, liquid crystals, and lubricants.
With all these applications and seemingly easy availability of these compounds, it is interesting to learn that original synthetic methods are still being employed today. As such, the objective of this Thesis is to develop ‘greener’ routes for the synthesis of fluorocarbons. We hypothesized that by studying transition metal-fluoroalkyl complex-mediated reactions, a more efficient catalytic system could be developed. A foreseen complication arises from the thermodynamic stability of C-F, transition metal-F and transition metal-CRF bonds. Improvements to overcome these caveats include the use of first-row late transition metal complexes. Presented herein are additions to this body of knowledge by expanding on the reactivity of nickel, copper and silver fluoroalkyl complexes.
The approach applied in this work, in line with ‘green’ chemistry principles, was to source readily available fluorinated reagents, i.e. fluoroalkenes and fluoroarenes, to reduce the number of steps for the synthesis of new fluorinated compounds. Chapter 2 builds on the well-established oxidative cyclization of C2 fluoroalkenes to nickel (0), which yields new C4 units. The use of a bulky N-heterocyclic carbene ligand was found to enhance reactivity by reducing the coordination number at nickel. Examples of room temperature Cα-F and Ni-CF bond activation and functionalization reactions are presented. Chapters 3, 4 and 5 re-examine the insertion of fluoroalkenes into silver and copper fluorides and hydrides. Building on precedent of addition reactions to hexafluoropropene, this fluoroalkene was examined first. In so doing, a versatile and inexpensive copper heptafluoroisopropyl reagent was developed (Cu-F addition to (CF3)CF=CF2. With easy access to new heptafluoroisopropyl complexes, they were systemically studied for their applications in catalysis. This revealed key features, particularly the lability of the M-hfip bond, which could be detrimental to catalytic reactions. As such, a nickel complex-mediated carbonylative heptafluoroisopropylation reaction and copper complex-mediated nucleophilic addition to electrophiles were developed. When a copper hydride was used instead, the in situ generated fluoroalkyl [Cu-H addition to (CF3)CF=CF2] was susceptible to β-fluoride elimination. Chapter 4 expands this methodology to achieve the catalytic consecutive hydrodefluorination of fluoroalkenes, demonstrating the scope and limitations of this system. Furthermore, the critical role of the phosphine ligand in accessing an L3Cu-H addition and unusual β-fluoride elimination mechanism is highlighted. However, tetrafluoroethylene proved resistant to this reaction because the fluoroalkyl resting state of this alkene, Cu-CF2CF2H, is unusually robust. Chapter 5 investigates the utility of this fragment and others in C(sp2)-RF cross-coupling and nucleophilic substitutions. With focus on new routes for late stage fluorination and examples of nickel (0) complex-catalyzed selective C-F bond functionalization reactions, Chapter 5, continues studies for low-temperature and DMAP-assisted conditions for aryl-F cross-coupling reactions with boronic acid esters.
Lastly, Chapter 6 reviews the advances presented in this Thesis, provides a link to the expected lasting impacts and attempts to provide guidance to future research on transition-metal complexes in the synthesis of C-F or C-RF containing compounds. Moreover, with the introduction of a new hydrodefluorination technology, previously scarce fluoroalkenes (e.g. 1,2-difluoroethylene) can now be used more freely, potentially leading to the development of new refrigerants or materials applications.
| Identifer | oai:union.ndltd.org:uottawa.ca/oai:ruor.uottawa.ca:10393/39509 |
| Date | 13 August 2019 |
| Creators | Andrella, Nicholas Orlando |
| Contributors | Baker, R. Tom |
| 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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