Presented in this thesis are the results obtained from the project: Asymmetric synthesis of substituted 2-aminotetralins. The initial goal was to establish new or improved routes to enantiopure 2-aminotetralin (2-AT) derivatives. The motivation for this project was based on the diverse applications various 2-ATs represent as biologically active compounds. Despite the role of 2-aminotetralins as interesting target molecules, reflected by the massive research activity in the field, no general and cost efficient route has really been established. Chapter 1 in this thesis gives an introduction to 2-ATs as biologically active compounds, as well as a brief survey of the concepts of chirality and asymmetric synthesis. Aziridines are also presented, given their role as key intermediates in our developed strategies (chapters 2-4). In chapter 2, a total synthesis of substituted (S)-2-ATs is presented, starting from natural L-aspartic acid. Two 2-AT derivatives were successfully synthesised, but especially one step (ring-closing to tetralones) proved difficult, providing up to 41% yield only. Chapter 3 is directly based on the experiences we made in the former chapter, and presents an improved route from the same starting point (chiral pool strategy utilising L-aspartic acid). Again we struggled with one specific cyclisation reaction (up to 36% yield), but the remaining steps provided overall good yields. In Chapter 4, a different approach has been targeted, i.e. asymmetric aziridination of 1,2-dihydronaphthalenes. Here, various copper, rhodium and ruthenium catalytic systems were tested with alternative nitrogen sources. While we were able to achieve quite good results for non-substituted 1,2-dihydronaphthalene, substituted substrates provided only mediocre yields and enantioselectivity. Aziridines were selectively ring-opened by catalytic hydrogenation to their respective N-protected 2-ATs in good yields.

No description available.

Thesis (Ph. D.)--Brigham Young University. Dept. of Chemistry and Biochemistry, 2007. / Includes bibliographical references.

The work described in this thesis is an investigation into the reactivity and possible synthetic applications of aziridinylcarbinyl radicals. These radicals rapidly rearrange via β cleavage, which can proceed by breakage of either the CoN or C-C bond. Cleavage of the latter has been found when the molecule has a phenyl stabilising group attached to the aziridine ring. Chapter I is a review of the known radical reactions involving aziridines whilst chapter 2 discusses the various methods of aziridine syntheses. Chapter 3 outlines the project aims with reference to the potential of directed cleavage of aziridinylcarbinyl radicals in synthesis. Chapter 4, the main body of the work, describes the synthetic routes to aziridines derived from 3-phenyl-2-cyclohexen-I-one and indenone. The radical mediated β-cleavage reactions of these is reported and the selectivity of C-C v. CoN bond homolysis has been investigated. Two successful approaches to the target aziridines were involved. I) Conversion of 3-azido-3-phenylcyclohexan-I,2-diol, derived from the epoxide of 3- phenyl-2-cyc1ohexen-I-ol, to the aziridine via reaction with triphenylphosphine. Subsequent methylation and formation of the thiocarbonylimidazolide gave the radical precursor Nmethyl- 5-[imidazol-I-yl(thiocarbonyl)oxy]-I-phenyl-7-azabicylo[4.1.0]heptane. In the course of this work, several unusual cyclic thiocarbonates resulting from the reaction of 3-azido-3- phenylcyclohexan-I,2-diol and 2-azido-3-phenylcyclohexan-I,3-diol with I, I 'thiocarbonyl diimidazole were isolated. 2) Formation of N-(2-ethylquinazolinonyl)-I-phenyl-7-azabicyclo[4.1.0]heptan-5-01 from the reaction of 3-amino-2-ethyl-4(3H)-quinazolinone with 3-phenyl-2-cyc1ohexen-I-ol in the presence of lead tetraacetate. These aziridines show interesting acid-catalysed rearrangements to diazadioxabicyclo[2.2.2]octanes. Formation of the thiocarbonylimidazolide then gave the radical precursor. A number of other aziridines have been prepared using this methodology. It has been found that in all cases the precursors undergo CoN bond homolysis under radical conditions. These results are discussed and conclusions are drawn. Suitable future work is also suggested.

Aziridines are important building blocks for the synthesis of a wide range of organic compounds, including biologically active compounds and pharmaceuticals. The development of more cost-effective catalysts for atom transfer reactions is a continuing area of research in chemistry. Transition metal complexes have been shown to catalyze the aziridination of olefins, however, most require expensive metal ions or complex ligands. Meso-tetra(N-methyl-4-pyridyl)porphyrin (TMPyP4) is a highly charged, planar ligand that has been used to support manganese(III) in complexes like Mn[TMPyP4]I5. Herein we report the optimization of the reaction conditions for the aziridination of olefins in water and buffered solutions catalyzed by Mn[TMPyP4]I5. The reaction conditions optimized include pH range, temperature, and reaction time. Additionally, nitrogen sources, nitrogen source/olefin ratios, and catalyst loading were optimized. In buffered solutions, Mn[TMPyP4]I5 can effectively catalyze the generation of aziridines from various aromatic and aliphatic olefins with Chloramine T in moderate to good yields (43-93 %).

Thesis (M.Sc.(Chemistry))--University of Pretoria, 2000. / Includes abstracts in Afrikaans and English. Includes bibliographical references (leaves 58-59).

Modern organic synthesis typically centers around the use of expensive, complex, homogeneous catalyst systems in organic solvents which often generate copious amounts of hazardous waste. Therefore, the development of water-tolerant catalysts capable of performing reactions in aqueous solutions has become a growing area of scientific inquiry. To this end, we have designed and optimized a water-stable catalyst (Mn[TMPyP4]I5) capable of generating aziridines from olefins in aqueous solutions. Aziridines are valuable synthetic building blocks that have been used to generate various biologically active compounds, though synthetic techniques for aziridine synthesis are not well-established. Our ultimate goal was developing a catalytic system, which could be paired with DNA in order to perform asymmetric transformation in aqueous solutions. Herein we report the optimization of reaction conditions using Mn[TMPyP4]I5 paired with various DNA types, in the hopes of generating chiral aziridines from several olefinic substrates.

La partie principale de ce manuscrit traite du développement de nouvelles méthodologies utilisant la substitution propargylique catalysée par des sels de fer(III), pour la formation de divers hétérocycles azotés (∆4-isoxazolines, isoxazoles, cis-acylaziridines et pyrimidines). En premier lieu, de nouvelles synthèses monotopes de ∆4-isoxazolines et d'isoxazoles diversement substitués impliquant des réactions de cyclisation catalysées par diverses espèces carbophiles ([Au], [Pd], [I+]) ont été développées. La fragilité de la liaison N-O des ∆4-isoxazolines a pu être ensuite exploitée pour conduire à la formation de cis-acylaziridines. De nouvelles voies d'accès aux (Z)-β-énaminones et aux pyrimidines trisubstituées ont été également développées. / The main part of this manuscript deals with the development of new methodologies using iron(III)-catalyzed propargylic substitution, for the synthesis of various nitrogen-containing heterocycles (Δ4-isoxazolines, isoxazoles, cis-acylaziridines and pyrimidines). Firstly, new one-pot syntheses of variously substituted Δ4-isoxazolines and isoxazoles involving cyclization reactions promoted by various carbophilic species ([Au], [Pd], [I+]) have been developed. The weakness of the Δ4-isoxazoline N-O bond has been then exploited, leading to the formation of cis-acylaziridines. New pathways to (Z)-β-enaminones and trisubstituted pyrimidines have also been developed.

New imidazotetrazinones have been synthesised that possess features in their structures to release aziridinium ions upon ring opening. Unstable 2-aminoethylisocyanates were required in this preparation, which were synthesized with BOC-protection of the amino group to counteract the reactivity of the amine towards the isocyanate group in the case of aliphatic amines; in contrast, anilinoethylisocyanates were synthesized unprotected. Substituents with a range of electron-withdrawing and electron-releasing properties were introduced at the p-position of the aniline ring. A 13C-labelled study confirmed the release of the aziridinium ion by these imidazotetrazinones in neutral pH buffer solution. Furthermore the kinetics of the hydrolysis in neutral aqueous solution of some these new tetrazines were similar to temozolomide, in addition to useful acid stability. Other imidazotetrazinones were synthesised for the purpose of releasing alcohols and phenols. Their synthesis was performed with a one-carbon linker between the imidazotetrazinone 3-position and the alcohols or phenols to be released. The release of alcohol and phenol through the hydrolysis of the intermediate diazonium ions to the unstable hemiacetals that decomposed to the alcohol and phenol was confirmed by 1H NMR. The kinetics of the hydrolysis of these tetrazines in neutral aqueous solution showed a faster reaction rate compared with temozolomide (t1/2 = 0.53 and 0.36 h compared with temozolomide 1.4 h).

In biological systems, most of the active organic molecules are chiral. Some of the main constituents of living organisms are amino acids and sugars. They exist predominantly in only one enantiomerically pure form. For example, our proteins are built-up by L-amino acids and as a consequence they are enatiomerically pure and will interact in different ways with enantiomers of chiral molecules. Indeed, different enantiomers or diastereomers of a molecule could often have a drastically different biological activity. It is of paramount importance in organic synthesis to develop new routes to control and direct the stereochemical outcome of reactions. The aim of this thesis is to investigate new protocols for the synthesis of complex chiral molecules using simple, environmentally friendly proline-based organocatalysts. We have investigated, the aziridination of linear and branched enals, the stereoselective synthesis of β-amino acids with a carbene co-catalyst, the synthesis of pyrazolidines, the combination of heterogeneous transition metal catalysis and amine catalysis to deliver cyclopentenes bearing an all-carbon quaternary stereocenter and a new heterogeneous dual catalyst system for the carbocyclization of enals. The reactions presented in this thesis afforded the corresponding products with high levels of chemo-, diastero- and enantioselectivity. / <p>At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 5: Submitted. </p>