This thesis is composed of three separate parts. Part I describes the synthesis of a series of 1-carbomethoxy-4-alkyl(aryl)-1,4-dihydro-pyridines by the reaction of pyridine with lithium phenylthio(alkyl or aryl)cuprate reagents in the presence of methyl chloroformate. In general, the yields of the reactions were reasonably good and the reactions were very regioselective. The efficiency of lithium phenylthio(alkyl or aryl)-cuprate reagents in the preparation of 4-alkyl-1,4-dihydropyridine derivatives was compared with that of lithium dialkyl(aryl)cuprates. It was found that, in most cases, the former reagents offered no advantages over the latter reagents. The use of electrophiles other than methyl chloroformate was also investigated. Acetyl bromide gave reasonable yields of the corresponding 4-alkyl-1,4-dihydropyridine derivatives but when chlorotrimethylsilane and diethylphosphorochloridate were employed, the yields of the corresponding 4-alkyl-1,4-dihydropyridine derivatives were fairly poor. Finally, the 1-carbomethoxy-4-alkyl-1,4-dihydropyridines prepared as outlined above were transformed in good yields into the corresponding 4-alkylpyridines by treatment of the former with methyl-lithium, followed by oxidation of the resulting 1-lithio-1,4-dihydropyridine derivatives with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone. The synthesis of 1-carbomethoxy-4-alkyl(aryl)-1,4-dihydropyridinesand their subsequent conversion into the corresponding 4-alkylpyridines introduces a new and fairly efficient way of synthesizing these compounds. Part II describes the synthesis and thermal rearrangement of a number of β-cyclopropyl-⍺,β-unsaturated ketones and in certain cases, their trimethyl- silyl enol ether derivatives. The β-cyclopropyl-⍺,β-unsaturated ketones were prepared in good yields from the corresponding β-iodo enones by treating the latter with lithium phenylthio(cyclopropyl)-cuprate. The β-iodo enones were obtained in good yields by the reaction of the corresponding β-diketones and a-hydroxymethylenecycloalkanones with triphenylphosphine diiodide. When the cyclic β-cyclopropyl-⍺, β-unsaturated ketones were thermolyzed, they underwent the expected vinylcyclopropane-cyclopentene rearrangement, giving the corresponding annelated cyclopentenes in reasonable yields. In the case of ⍺-cyclo-propylmethylenecycloalkanones, pyrolysis of the corresponding trimethyl-silyl enol ethers gave better yields of the corresponding spiroannelated cyclopentenes than did pyrolysis of the parent enones. This new spiro cyclopentene annelation reaction was applied to the preparation of the spiro ketone 198, a key intermediate for the synthesis of a number of spirovetivane sesquiterpenes. The key steps in the synthesis of the spiro ketone 198 involved the preparation and thermolysis of the trimethylsilyl enol ether 200. Copper catalysed conjugate addition of methyl magnesium iodide to 2-cyclohexen-1-one, followed by trapping of the resulting enolate anion with cyclopropanecarboxaldehyde gave the β-hydroxyketone 203 in ~98% yield. Overall dehydration of 203, via base-promoted elimination of acetic acid from the corresponding acetate 211 gave a 78% yield of a mixture of the g-cyclopropyl enones 155 and 156, in a ratio of 13:1, respectively. Treatment of the latter mixture with lithium diisopropylamide, followed by trapping the resulting enolates with chlorotrimethylsilane gave the enol silyl ethers 200 in ~95% yield. Pyrolysis of 200, followed by hydrolysis of the crude product, gave a 57% yield of a mixture of the spiro enone 212 and 213, in the ratio of 2.5:1, respectively. The desired isomer 212 was isolated from the mixture and was subsequently transformed into the spiro ketone 198 via a straightforward, four-step sequence of reactions. Part III describes the synthesis and thermal rearrangement of the tricyclic enones 39 and related compounds. Reaction of lithium phenylthio(syn-7-norcar-2-enyl)cuprate (38) with 3-iodo-2-cyclohexen-l-one and 3-iodo-2-cyclopenten-1-one gave the tricyclic enones 55 and 56, respectively. It was thus clear that the initially formed enones 39 underwent facile Cope rearrangement to give the tricyclic enones 55 or 56 during work-up and/or purification. Reaction of a 1:1 mixture of syn and anti lithium phenylthio(7-norcar-2-enyl)cuprates with 3-iodo-2-cyclohexen-l-one gave a 1:1 mixture of the tricyclic enones 55 and 57. Similarly, reaction of the same cuprate reagent mixture with 3-iodo-2-cyclopenten-1-one gave a 1:1 mixture of the enones 56 and 58. When o-dichlorobenzene solutions of the enones 57 and 58 were refluxed, these compounds readily rearranged to the tricyclic enones 55 and 56, respectively. / Science, Faculty of / Chemistry, Department of / Unknown

No description available.

No description available.

This paper deals with the preparation of pyridinium derivatives of naphthoquinone. The starting material was 2,3-dichloro-1,4-naphthoquinone, and it was reacted with pyridine and 4-n-alkyl-pyridine derivatives.

Acyl-transfer reactions have become commonplace in organic synthesis and organocatalysis of these reactions is becoming increasingly popular. 4-Dimethylaminopyridine has proven to be very useful in acylations; over the recent years chiral and more reactive analogs have received much attention. Interestingly, catalysis of acyl-transfers by diamines has also been shown to be effective. We present the synthesis of several DMAP analogs containing heteroatoms near the nucleophilic nitrogen. These analogs of DMAP vary from basic amidines, oxazolines, and amines, to alcohols, and fluoro-derivatives all of which may provide hydrogen bonding to the alcohol undergoing acyl-transfer. Since Steglich proposed the need for a base in the DMAP catalyzed acyl-transfer transition state no studies have been performed on the effect that nearby hydrogen bonding or nearby bases might have on catalytic efficiency and enantioselectivity of acylations. The variety of compounds synthesized should allow for studies into rate and selectivity enhancements in nucleophilic pyridine catalysis.

No description available.

No description available.

A series of <i>N</i>-acylated and –alkyated aminobromopyridines were prepared, and under 2,2’-azobisisobutyronitrile (AIBN) initiation in the presence of <i>n</i>-tributyltin hydride (Bu₃SnH), readily underwent cyclisation to produce 4-aza and 7-azaoxindole derivatives. Upon recrystallisation in polar solvents in the presence of atmospheric oxygen, these compounds were found to undergo quantitative autoxidation.  Inspection of NMR and MS data suggest that the mechanism proceeds by hydrogen abstraction to form a hydroperoxide intermediate. The second part of the study reveals a simple and effective synthesis towards pyrrolo[2,3-<i>d</i>]pyrimidine derivatives as substitutes for purine analogues.  The purine-type nucleus is secured <i>via </i>tributyltin hydride mediated radical cyclisation, which provides a convenient route to access compounds for studies of biological activity and structure activity relationships. The third part describes radical addition of iodopyridines and functionalised pyrimidines to arenes, effected under mild conditions using tris(trimethylsilyl)silane and oxygen to promote the bimolecular radical addition pathway.  Initial reactions yielded intractable pyridine products with tris(trimethylsilyl)silane by-products. This was overcome by initial quaternisation of the heterocycles. The fourth part of the study  concerns the synthesis of the pyrimidine backbone unit of the natural product isolated from the <i>heterostemma brownii.  </i>This was obtained by the regioselective radical addition of halopyrimidine to electron-deficient methyl methacrylate (MMA). The final part describes the radical translocation reaction and the effect of variation in cycloalkane ring sizes and electron-donating ability.  This provided a route towards horsfiline derivatives. Under the high temperatures experienced by the horsfiline precursors this serendipitously yielded macrocyclic pyrimidines.

Chapter 1 provides an overview on the chemistry of pyridines and aminopyridines, their biological activities and their synthesis using Bohlmann-Rahtz, Hantzsch and Chichibabin methodology. It discusses the application of modern alternative reaction platforms, such as microwave-assisted synthesis and flow chemistry, of relevance to the synthesis and reactions of pyridine derivatrives. Chapter 2 discusses Lewis acid catalysis in the Bohlmann-Rahtz pyridine synthesis and describes new one-pot, two- and three-component methodologies that have been developed for the synthesis of natural products containing the pyridine motif. These methods have been compared and contrasted and applied to the use of tetranuclear coordination clusters as Lewis acid mixed metal catalysts for Bohlmann-Rahtz cyclodehydration and pyridine synthesis. Chapter 3 discusses the use of the Bohlman–Rahtz pyridine synthesis for the preparation of a range of fused heterocycles containing the pyridine moiety in high yield, including 1,3,7-trimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, 1,3-dimethyl-7-phenylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione, 1,7-dimethylpyrido[2,3-d]pyrimidine-2,4(1H,3H)dione and 1-methyl-7-phenylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione. Chapter 4 describes new substrate scope for the Bohlmann-Rahtz pyridine synthesis by incorporating an amino group at the 2-position of the products. The synthesis of a range of 2,3,6-trisubstituted and 2,3,4,6-tetrasubstituted pyridines was accomplished with total regiocontrol using this new method under microwave-assisted conditions. Chapter 5 describes a new microwave-assisted method for the synthesis of poly-deuterated pyridines. The microwave mediated deuteration of aminopyridine derivatives both with and without the presence of DCl has been studied. The regioselectivity and yields for these processes were compared. Following discovery of a new method for single cycle H/D exchange at multiple positions, high yield and high levels of deuterium incorporation have been found for a range of substrates.

Di-2-pyridinylmethanone (di-2-pyridyl ketone) is a well-known ligand within the family of basic building blocks for the construction of metal-organic complexes with diverse architectures and potential applications in relation to their physical and chemical properties. A systematic investigation on the generation and structure of transition metal complexes based on six ligands containing the dipyridinylmethanone moiety is reported in this thesis. Although all these ligands are known except L7, their coordination chemistry remains unexplored to date. / Ligand 2-pyridinyl-3-pyridinylmethanone (L1) is an excellent building block for the construction of infinite single-strand helical architectures with various metal salts. In the resultant helical complexes, Ll exhibits three kinds of coordination modes involving two kinds of bridging conformations, resulting in four types of single-strand helical chains. Among them is a pair of helical conformational polymorphs generated by the solvent-controlled process, in which the 21 helices of opposite chirality in one are stacked alternately to form a racemate, whereas the 41 helices in the other are assembled homochirally by inter-chain argentophilic interaction to generate a conglomerate. In a series of six isostructural 21 helical Ag(I) complexes, the pitch length corresponds not only to the size of the embedded anion but also to the manner of its fitting into the groove of the helix. In the Co(II) and Zn(II) complexes that comprise helical chains without anion embedment, the pitch lengths are dictated by the size of the metal cations. / Ligand 2-pyridinyl-4-pyridinylmethanone (L2) readily gives rise to dimeric metallacyclophanes with various Ag(I) salts, which bear close structural similarity. An ordered sequence of the coordinating ability of a series of nine polyatomic monoanions has been established on the basis of structural parameters derived from their interaction with a common disilver(I) metallacyclophane skeleton in isostructural complexes. The reactions of L2 with Co(II), Cu(II), Zn(II) and Cd(II) salts give rise to supramolecular architectures assembled through weak interactions including hydrogen bonding and pi&middot;&middot;&middot;pi stacking, in which L2 adopts various ligation modes. / Metal complexes of 3-pyridinyl-4-pyridinylmethanone (L4) exhibit a variety of structural types: single chain, ladder-like chain, (4,4) network and tetrameric unit. (Abstract shortened by UMI.) / Chen Xudong. / "July 2005." / Adviser: Thomas C. W. Mak. / Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 3787. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 143-164). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract in English and Chinese. / School code: 1307.