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Naturally occurring quinones have attracted considerable interest due to their widespread occurrence, structural diversity and often potent biological activities. The research outlined in this thesis involves the development of synthetic approaches to two novel naphthoquinone derivatives, both of which were discovered during investigations into the bioactive constituents of tropical plant species. Chapter 1 introduces the family of quinonoid compounds and also considers the important role that natural product synthesis can play in structural confirmation and in providing an adequate supply of compounds for further research. Chapter 2 describes the synthesis of elecanacin 36, an unusual cyclobuta-fused naphthalene-1,4-dione derivative which has been isolated from the bulbs of the iris Eleutherine americana Merr. et Heyne (Iridaceae), along with the isomeric and well-known pyranonaphthoquinones eleutherin 38 and isoeleutherin 39. Chapter 3 focuses on an approach to 3-hydroxymethylfuro[3,2-b]naphtho[2,3-d]furan-5,10-dione 37, which has been isolated from the wood of the tropical tree Crescentia cujete L. (Bignoniaceae) and incorporates a rare fully aromatic furofuran moiety.

Our group recently discovered and developed a diastereoselective reaction yielding C3-quaternary indolenines from the combination of α,β-unsaturated N-aryl ketonitrones and mono- or di-activated alkynes in toluene at 80 °C. This reaction builds a high level of complexity in a single step, and the C3-quaternary indolenines produced show promise as precursors to indole-containing molecules of biological and medicinal interest. However, we found our substrate scope was limited by the methods available for the synthesis of the α,β-unsaturated N-aryl ketonitrones necessary for the reaction. As a result of this need, we sought to develop a new way to access these α,β-unsaturated N-aryl ketonitrones. Our priorities were to develop a method that was expedient with regard to time and number of steps, modular, general, and could rely on inexpensive commercially available starting materials. The method that we have reported proceeds in three steps: starting with a commercially available aniline derivative and α,β-unsaturated aldehyde an imine is synthesized and alkylated using an organolithium reagent. The resultant secondary amine is then oxidized using Oxone® to obtain the α,β-unsaturated N-aryl ketonitrone. Only the nitrone is subject to a discrete purification step, and it can generally be isolated in yields of 50-80%. Unfortunately, the nitrones generated using this technique would not react with activated alkynes to yield indolenines. The two techniques discussed herein offer valuable insight into a poorly understood area of nitrone reactivity and are both synthetically useful in their own right. The studies performed make it clear that nitrones are a very viable synthetic intermediate; many nitrones can be easily accessed and then used to create very complex molecules in a diastereoselective manner. Both of these synthetic techniques in combination offer a valuable alternative approach to many complex and biologically interesting indole containing alkaloids. It is hoped that this work will serve as fertile ground for further studies towards increasing the utility of this chemistry.

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.

Microwave reactors are important tools in chemical synthesis, as they can lead to unprecedented reductions in reaction times and improved reaction yields. In order to scale-up the technology for greater throughput and industrial application, reactor types are moving from batch to continuous flow reactors. This research designed, built, verified and modeled a continuous flow microwave reactor. The reactor could operate under high temperature/high pressure conditions, and was connected to in-line gas chromatography/mass spectrometry, for real time sample analysis. Specifically, a pressure device was developed to enable the reactor to run under high pressure conditions (< 1100 psi) without the use of a conventional back-pressure device. The reactor design was verified using two chemical reactions, and an in-line analytic apparatus was developed to assess the potential for reactor operation with in-line GC/MS. Additionally, a computational fluid dynamic model was developed to better understand the heat and mass transfer inside the reactor.

Microwave reactors are important tools in chemical synthesis, as they can lead to unprecedented reductions in reaction times and improved reaction yields. In order to scale-up the technology for greater throughput and industrial application, reactor types are moving from batch to continuous flow reactors. This research designed, built, verified and modeled a continuous flow microwave reactor. The reactor could operate under high temperature/high pressure conditions, and was connected to in-line gas chromatography/mass spectrometry, for real time sample analysis. Specifically, a pressure device was developed to enable the reactor to run under high pressure conditions (< 1100 psi) without the use of a conventional back-pressure device. The reactor design was verified using two chemical reactions, and an in-line analytic apparatus was developed to assess the potential for reactor operation with in-line GC/MS. Additionally, a computational fluid dynamic model was developed to better understand the heat and mass transfer inside the reactor.