Exploring Noncovalent and Reversible Covalent Interactions as Tools for Developing New Reactions

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.Ph