The central theme of the research described in this thesis involves taking advantage of the reversible covalent interactions of organoboron species with diols, and exploiting them as catalyst-substrate interactions. Using this philosophy, novel catalytic transformations have been developed to form carbon-carbon and carbon-oxygen bonds.
Chapter 1 describes a method that uses organoboron species to activate pyruvic acids in the direct aldol reaction with aldehydes. Formation of an anionic tetracoordinate boron adduct was the key step in the proposed mechanism. A wide range of aldehydes may be employed, delivering useful isotetronic acid products in high yields.
The efficient synthesis of oligosaccharides requires methods for regioselective manipulation of hydroxyl groups in monosaccharides. Catalysis represents a potentially general solution to this problem, and recently, the development of catalyst-controlled methods towards this goal has intensified. Chapter 2 highlights the range of catalysts that may be exploited to alter the reactivity of hydroxyl groups in carbohydrates.
Chapter 3 describes a novel diphenylborinic acid-catalyzed protocol, which enables the site-selective functionalization of carbohydrate derivatives and non-carbohydrate-derived 1,2- and 1,3-diols with a wide diversity of electrophiles. Mechanistic details of the organoboron-catalyzed processes are explored using competition experiments, kinetics and catalyst structure-activity relationships. These studies are consistent with reaction of a tetracoordinate borinate complex with the electrophilic species in the turnover-limiting step of the catalytic cycle.
Chapter 4 further explores the utility of borinic acid activation in the first small-molecule-catalyzed glycosylation reaction of unprotected or minimally protected glycosyl acceptors. High levels of selectivity for the equatorial hydroxyl group of cis-1,2-diol motifs are demonstrated in reactions of several glycosyl acceptors using a variety of glycosyl halide donors.
Chapter 5 describes a novel mode of catalysis using a boronic acid/Lewis base co-catalyst system. The proposed mode of activation involves the formation of a tetracoordinate adduct that displays enhanced nucleophilicity at the boron-bound alkoxide groups. This concept was applied to the regioselective silylation of carbohydrate derivatives as well as the desymmetrization of diols.
Finally, Chapter 6 summarizes the work described in this thesis, discusses the challenges encountered in the development of the methodologies, and speculates on future directions that can be taken.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/43646 |
| Date | 10 January 2014 |
| Creators | Lee, Doris |
| Contributors | Taylor, Mark S. |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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