Explorations into the reactivity of vinyl ruthenium and gold carbenes and the development of methods for the removal of transition metal catalysts
French, Jonathan Murray
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Chapter 1: Cationic gold catalysis has been widely employed in synthesis due to the mild reaction conditions and chemoselectivity offered by the cationic gold catalysts. Commonly these catalysts are used to electrophilically activate an internal alkyne to attack from a pendant nucleophile. If the pendant nucleophile is an acetate the resulting rearrangement is known as the Rautenstrauch rearrangement, if the pendant nucleophile is another heteroatom the subsequent endo or exo dig cyclization can occur. A substrate with an internal alkyne was designed containing both a pendant acetate and a pendant sulfonamide nucleophile to investigate the electronic and steric factors which are important for allowing one reaction pathway to account for major product formation. The results of this study demonstrate that steric and electronic factors play a small role in altering the selectivity of the 5- endo -dig cyclization which was observed as the major reaction pathway. Chapter 2: With the increase in the application of alkene metathesis within challenging systems, the issue of chemoselectivity arose. In a molecule with more than one alkene of equal reactivity, product mixtures arose from competing catalyst initiation. To circumvent this issue a relay tether could be installed to selectively direct the reaction sequence. Due to the ability of the relay concept to improve the reactivity of several alkene metathesis reactions we were interested in developing the methodology for application in enyne metathesis. The relay concept was able to increase yield in challenging enyne metathesis reaction such as chiral allylic alcohols and geminally substituted alkenes, a substrate previously unreactive in intermolecular enyne metathesis reactions. Chapter 3: One of the remaining challenges associated with ruthenium carbene catalyzed metathesis reactions is the removal of the metal from the desired product once the reaction is complete. This residual metal can lead to product decomposition or isomerization as well as lead to issues if the material is to be used for biological testing. As a result a method was needed which could quickly and efficiently destroy catalyst activity as well as separate the metal from the product. Previously in the group an isocyanide ligand was developed for this purpose, however the compound was still not user friendly. A second generation material was made in which the isocyanide ligand was immobilized on the surface of silica gel. This material provided effective removal of a wide variety of commercially available ruthenium metathesis catalysts. An initial crude reaction could be reduced from 11,000 ppm to between 5-6 ppm residual metal through a single treatment. In combination with standard column chromatography this method could provide levels of residual metal which were less than 1 ppm. Chapter 4: Alkene and enyne metathesis result in product mixtures of E and Z -isomers. Often this distribution is dictated by substrates. Metathesis would be synthetically more useful if a catalyst could dictate the product distribution of the reaction. A catalyst which could selectively form the E or Z -isomer would allow for more efficient use of the catalysts in synthesis. In this project a unique family of meso -NHC ligands was developed in an effort to create a Z -selective catalyst. All of the newly synthesized catalysts were more Z -selective than the parent catalysts, however, none were Z -selective.