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Noncovalent and reversible covalent interactions have long been exploited in catalysis and supramolecular chemistry. Examples of such noncovalent interactions include hydrogen bonding, halogen bonding and CH-π and π-π interactions. Reversible covalent interactions that have been employed towards these ends comprise the formation of imines, acetals, ketals and boronate esters. This thesis describes the investigation of various noncovalent and reversible covalent interactions, and their possible applications in catalysis and novel reaction development. Chapter 1 describes the investigation of anion receptors composed of hydrogen- and halogen- bond donor groups. Binding studies of these molecules have indicated that they are capable of interacting with an anion simultaneously through hydrogen and halogen bonding. Receptor design was found to have a profound effect on the strength of the halogen bonding interaction. Receptors containing halogen-bond donors showed selectivity for halide anions over oxyanions. In Chapter 2, potential halogen bonding catalysts were synthesized and screened in a series of reactions. Incorporating halogen-bond donors into the catalysts appeared to have no beneficial effect in terms of reactivity. Explanations for these observations are discussed along with suggestions for designing future catalysts that could exploit halogen bonding interactions. Chapter 3 discusses attempts to use hydrogen-bond donor catalysts to effect catalyst-controlled stereoselective additions to 2-nitroglycals. While stereoselective additions were observed in some cases, they were not catalyst-controlled. The results from these experiments suggested that catalysts and reactions developed for simple nitroalkenes could not be easily adapted to 2-nitroglycal substrates. A review of interactions between boron containing compounds and saccharides is presented in Chapter 4. Their applications in drug delivery systems, cellular imaging and the sensing and separation of carbohydrates are discussed, in addition to their uses as protecting and activating groups in oligosaccharide synthesis. Finally in Chapter 5, the development of a regioselective boronic acid-mediated glycosylation reaction is described. This methodology was applied in the synthesis of two key intermediates used in the synthesis of a pentasaccharide derivative isolated from the plant Spergularia ramosa.

Noncovalent and reversible covalent interactions have long been exploited in catalysis and supramolecular chemistry. Examples of such noncovalent interactions include hydrogen bonding, halogen bonding and CH-π and π-π interactions. Reversible covalent interactions that have been employed towards these ends comprise the formation of imines, acetals, ketals and boronate esters. This thesis describes the investigation of various noncovalent and reversible covalent interactions, and their possible applications in catalysis and novel reaction development. Chapter 1 describes the investigation of anion receptors composed of hydrogen- and halogen- bond donor groups. Binding studies of these molecules have indicated that they are capable of interacting with an anion simultaneously through hydrogen and halogen bonding. Receptor design was found to have a profound effect on the strength of the halogen bonding interaction. Receptors containing halogen-bond donors showed selectivity for halide anions over oxyanions. In Chapter 2, potential halogen bonding catalysts were synthesized and screened in a series of reactions. Incorporating halogen-bond donors into the catalysts appeared to have no beneficial effect in terms of reactivity. Explanations for these observations are discussed along with suggestions for designing future catalysts that could exploit halogen bonding interactions. Chapter 3 discusses attempts to use hydrogen-bond donor catalysts to effect catalyst-controlled stereoselective additions to 2-nitroglycals. While stereoselective additions were observed in some cases, they were not catalyst-controlled. The results from these experiments suggested that catalysts and reactions developed for simple nitroalkenes could not be easily adapted to 2-nitroglycal substrates. A review of interactions between boron containing compounds and saccharides is presented in Chapter 4. Their applications in drug delivery systems, cellular imaging and the sensing and separation of carbohydrates are discussed, in addition to their uses as protecting and activating groups in oligosaccharide synthesis. Finally in Chapter 5, the development of a regioselective boronic acid-mediated glycosylation reaction is described. This methodology was applied in the synthesis of two key intermediates used in the synthesis of a pentasaccharide derivative isolated from the plant Spergularia ramosa.

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.

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.

The oligosaccharide domain of many secondary metabolites have been demonstrated to be pivotal for the biological efficacy of the parent glycoconjugate. In most cases, the alteration or removal of these carbohydrate residues results in the greatly diminished or completely abolished biological activity of the natural product. A common structural motif found in secondary metabolites possessing carbohydrate domains is the 2-deoxy-β-glycosidic linkage which are among the most difficult to establish in a stereocontrolled fashion. Chapter I provides background information describing the difficulties associated with the synthesis of 2-deoxy-β-glycosidic linkages in addition to a sampling of the current methodology available for their construction. Chapter II details our use of diethyl and pinacol phosphite glycosyl donors towards a direct synthesis of a designed 2-deoxy-β-oligosaccharide in a "one-pot" process which constitutes a novel approach towards the synthesis of these glycosidic linkages. Lomaiviticin A was isolated as the major metabolite from fermentation of the halophilic strain LL-37I366 which was later assigned the name Micromonospora lomaivitiensis. Lomaiviticin A displayed potent biological activity towards numerous cancer cell lines with IC50 values ranging from 0.01 to 98 ng/ml. While postulated to induce double-stranded DNA cleavage, the mechanism of action was unique when compared to known DNA-damaging agents such as adriamycin and mitomycin C. Chapter III details progress towards the synthesis of lomaiviticinone employing an "inside-out" strategy to take advantage of the molecule's own C2-symmetrical nature. The focus of the chapter will pertain to our efforts to construct the stereochemically-rich cyclohexenone central core highlighted by the use of organometallic C-C bond formation processes.