Examination of the scope of the [Rh(CO)₂Cl]₂-catalyzed allylic substitution reaction as well as the development of a domino [Rh(CO)₂Cl]₂-catalyzed allylic alkylation/Pauson Khand reaction is described. A number of experiments were carried out in order to explore the novel regioselectivity in the [Rh(CO)₂Cl]₂-catalyzed allylic substitution reaction, and the [Rh(CO)₂Cl]₂-catalyzed allylic substitution reaction was found to give products resulting from attack of the nucleophile on the carbon bearing the leaving group in a highly regioselective fashion in most cases. Examination of allylic carbonate substrates containing similar substitution at each allylic site was carried out, and conditions that minimize equilibration of active intermediates were determined. Intramolecular [Rh(CO)₂Cl]₂-catalyzed allylic alkylation was accomplished to synthesize challenging eight-membered lactone ring systems. Nucleophile scope was explored with regards to the [Rh(CO)₂Cl]₂-catalyzed allylic substitution reaction, and malonates, substituted malonates, aliphatic amines, and ortho-substituted phenols were all determined to be effective in the reaction. A domino [Rh(CO)₂Cl]₂-catalyzed allylic alkylation/Pauson-Khand reaction was developed which allows the rapid synthesis of bicyclopentenone products from simple, readily available starting materials. The first application of the Pauson-Khand reaction to the synthesis of azabridged bicyclic structures is also described. Various cis-2,6-disubstituted piperidines were cyclized to the corresponding azabridged bicyclopentenones is high yields often in high diastereoselectivities. The effect of ring size, nitrogen substituent, and remote functionality on the Pauson-Khand substrates was studied. The methodology developed was applied to the concise, enantioselective total synthesis of the antimalarial and anticancer indole alkaloid (-)-alstonerine. Pauson-Khand reaction of a readily available enyne synthesized in four steps from L-tryptophan provided a cyclopentenone in high yield as one diastereomer. Elaboration of the Pauson-Khand product required the development of a one pot conversion of a five-membered cyclic silyl enol ether to a sixmembered lactone and the mild acylation of a glycal.

This thesis describes the preparation of a series of compounds containing π-excessive, five-membered, heterocyclic rings with peripheral aryl substituents, designed to investigate their oxidative cyclodehydrogenation and/or photocyclisation to form curved, fused aromatic systems with a heterocyclic atom at the core of the compound. The ability of these compounds to undergo oxidative cyclodehydrogenation was investigated using a range of conditions, including the use of Lewis acidic transition metals, organic reagents and light as catalysts to carry out the desired carbon-carbon bond forming reactions. Two backbone linked 2,2’-biimidazole ligands were prepared to investigate their coordination chemistry with a range of different metal ions and counter ions. Two families of model compounds, including ten previously unreported compounds, were prepared and subjected to various conditions for oxidative cyclodehydrogenation and photocyclisation resulting in the isolation of compounds with one carbon-carbon bond formed between the peripheral aryl rings in the same position on the heterocyclic ring, nineteen previously unreported compounds were isolated. Additionally, in one case oxidative cyclodehydrogenation resulted in the formation of two carbon-carbon bonds, producing a highly strained aromatic compound containing a heterocyclic ring. Photocyclisation of one family of compounds resulted in the formation of a different heterocyclic core dependent upon the substituent on the nitrogen atom. Five pentaarylpyrrole compounds, three of which were previously unreported, were also prepared after the exploration of various synthetic routes towards the pentaarylpyrrole motif. Photocyclisation also resulted in the formation of one carbon-carbon bond. The compounds resulting from oxidative cyclodehydrogenation and photocyclisation were characterised by NMR spectroscopy, UV/vis spectroscopy and fluorometry, where possible X-ray crystallography was also used. The coordination chemistry of backbone linked 2,2’-biimidazole ligands to various metal ions could be controlled by the length of the backbone linker. The ethyl linked 2,2’-biimidazole ligand formed bridging and monodentate coordination compounds with various metal ions, the metallosupramolecular assemblies produced with silver ions could be controlled by the anion present. Discrete coordination complexes were usually formed, but in two cases metallopolymers were produced. The propyl linked 2,2’-biimidazole ligand formed exclusively discrete, chelating complexes with copper (II) metal ions. Eighteen coordination complexes were prepared during the course of this study characterized by X-ray crystallography, and NMR spectroscopy where appropriate.

published_or_final_version / Chemistry / Master / Master of Philosophy

published_or_final_version / Chemistry / Master / Master of Philosophy

A series of substituted indoles have been synthesized by the sequential reaction of aromatic aldehydes with ethyl azidoacetate in the presence of sodium ethoxide to form the corresponding ethyl α-azido-β-arylacrylates (Knoevenagel process) followed by a solvent mediated thermolysis (Hemetsberger process). The isolated yields of the ethyl α-azido-β-arylacrylates were significantly increased when employing the sacrificial electrophile ethyl trifluoroacetate. 1H NMR and coupled 1H-13C NMR analysis of the ethyl α-azido-β-arylacrylates indicate that the condensation is stereospecific—only the Z-isomer could be detected. Solvent mediated thermal treatment of the meta-substituted ethyl α-azido-β-arylacrylates resulted in the formation of both the 5- and 7- substituted indoles—the 5-regioisomer being slightly favored over the 7-regioisomer. Analogous thermal treatment of (2Z, 2Z’)-diethyl 3,3’-(1,3-phenylene)bis(2-azidoacrylate) and (2Z, 2Z’)-diethyl 3,3’-(1,4-phenylene)bis(2-azidoacrylate) exclusively produced pyrroloindoles, diethyl 1,5-dihydropyrrolo[2,3-f]indole-2,6-dicarboxylate and diethyl 1,5-dihydropyrrolo[2,3-f]indole-2,6-dicarboxylate, respectively. Results are also reported which indicate that the α-azido-β-arylacrylates can be used in the subsequent Hemetsberger indolization process without prior purification. Organic substrates containing basic nitrogen centers have been problematic in achieving high yields in the Suzuki coupling process. The origin of this issue is attributed to the complexation of the basic nitrogen center with the palladium catalyst. As a consequence, the use of CO₂ at a variety of pressures was evaluated as a reversible protecting/activating reagent for basic nitrogen containing substrates. The following observations and conclusions were reached. (1) The use of small amounts of water significantly improves the rate and yield of Suzuki coupling reactions. (2) In the presence of aqueous CO₂, careful selection of the base is essential due to formation of bicarbonate and the associated decrease in the amount water. K3PO4 was found to be the most effective base in the presence of CO₂. (3) The yield of product in the Suzuki coupling of 4-amino-2-bromopyridine with phenylboronic acid was evaluated as a function of CO₂ pressure. Compared to reactions in the absence of CO₂, the yield of product increased at all pressures of CO₂ (6.8, 17, and 30.6 atm) - from 15% with no CO₂ to 73% with 30.6 atm of CO₂.

The quinoline-5,8-diones are an important class of compounds with a wide spectrum of biological activites such as antibacterial, antiasthmatic, antifungal, antitumour and antiparasitic agents. Over the past three decades many variously substituted derivatives of quinoline-5,8-diones have been synthesized and reported. The majority of them dealt with the chemistry of C-6 and/or C-7 substituted quinolinediones and were related to Lavendamycin. Our lab has developed several procedures for the condensation (Knoevenagel) and reduction of aldehydes and ketones with malononitrile. When this reductive alkylation procedure was attempted with quinoline-2-carboxaldehyde, a crude product was observed by NMR spectroscopy. This product rearranged upon attempted purification via recrystallization or column chromatography. The nucleophilic attack of the quinoline N on the C of the nitrile followed by a proton transfer and a tautomerization resulted in the creation of indolizine. We will study the reductive alkylation of a series of quinoline-5,8-diones with carboxaldehydes at the C-2 position with malononitrile. This reaction is carried out in 95% ethanol with no catalysts present. This reaction mixture is then diluted with additional 95% ethanol and then cooled in an ice/water bath before the addition of sodium borohydride (NaBH4) to afford the desired monosubstituted malononitrile. We have also carried out the reactions with a range of other substituted quinoline compounds. In these cases the indolizines were not observed. It is assumed that the indolizine product does not form due to the presence of substituents on the C-8 position. Additional studies will focus on unsubstituted C-8 quinoline rings to prepare other novel indolizines. Otherwise, various reactions are performed to force the formation of indolizine. / Introduction/background -- Preparation of quinoline derivatives and their respective carboxaldehydes -- Preparation of monosubstituted malononitriles and indolizines. / Department of Chemistry

Novel indolo-macrocycles have been generated from the attempts to synthesise bis-indolo-cyclotriveratrylenes by the condensation of I, I'-diindolyl-3,3'-dimethanols catalysed by p-toluenesulfonic acid. The addition of substituents on indoles led to enhanced solubilities of the macrocycles. Nine- and six-membered ring compounds have been synthesized from the acid-catalysed reaction of I,I'-diindolyl compounds and aryl aldehydes. Some reactions of these compounds and the attempted synthesis of 2,2' diindolylmethanes from the cyclic compounds have also been described. The electrophilic substitution reactions of 3-substituted 4,6-dimethoxyindole 2,6-dimethanols and 3-substituted 4,6-dimethoxyindole-7 and 2-carbaldehydes and I-substituted indoles afforded triindolyl dialdehydes. The wriation of substituents at C-7 of indole-7-aldehydes and at C-2 of indole-2-aldehydes has also been discussed. Reaction of the hydroxymethylindole and 1,2-di(indol-I-ylmethyl)benzene gave a new macrocycle. Substitution reactions of 2,2???-diindolylmethane-7,7'-dimethanol and indole-7- and 2-aldehydes gave tetraindolyl dialdehydes. Sodium borohydride reduction of tri- and tetra-indolyl dialdehydes gave tri- and tetra-indolyl dimethanols respectively. Acid-catalysed reactions of tri- and tetra-indolyl dimethanols afforded only calix[3] and [4]indoles respectively when all substituents at C-3 of indoles were aryl groups. New conditions for indole based imine synthesis have been established Macrocyclic imine formation from mono-, di-, tri and tetra-indolyl dialdehydes has been investigated. Reactions of indole-3, 7-dialdehydes and short chain diamines (1,2-diaminoethane, 1,2-diaminobenzene and 1,6-diaminohexane) gave mixtures while the reactions with long chain diamines (1,10 diaminodecane and 1,12-diaminododecane) gave monoindolyl macrocyclic imines. Reaction of indole-2, 7-dialdehydes and short chain diamines afforded diindolyl macrocyclic imines with head-tail structures, and the 2,7';2',2";7",2'''-Tetraindole-7 ,7"'-dialdehyde underwent cyclisation with triindolyl dialdehydes and 1,6-diaminohexane afforded triindolyl macrocyclic imines. 1,2 diaminoethane while the 2,3 ';1',1 ";3 ",2"'-tetraindole-7,7"'-dialdehydes underwent imine, with its precise structure established by X-ray crystallography. Reaction of of 1,3-di(indol-l-ylmethyl)benzene and 1,2 diaminoethane yielded a new macrocyclic reactions with long chain diamines yielded monoindolyl macrocyclic imines. Reaction ring closure with 1,2 diaminoethane and 1,6-diaminohexane.

Thesis (Ph.D)--University of Wollongong, 2005. / Typescript. Includes bibliographic references: p. 195-202.

Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains xv, 275 p. : ill. Includes abstract. Includes bibliographical references (p. 107-113).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1940. / Typescript. Includes abstract and vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 85-87, 105).