Chapter 1 outlines the development of a catalytic electrocyclic process and its exploitation in asymmetric synthesis. Since Woodward and Hoffmann delineated a rationale for the mechanism and stereochemistry of these reactions they have become powerful synthetic tools. The aim of this project was to investigate catalytic asymmetric 6π electrocyclizations that will enable the rapid synthesis of highly functionalized molecules. We have demonstrated that the transient hexatriene precursors for [1,6]-electrocyclization are difficult to synthesize. When possible the central cis-alkene prefers to exist in a trans-configured geometry, while the free ketone undergoes an essentially irreversible oxo-electrocyclization. However the precursors for [1,5]-electrocyclization could be assembled via the Suzuki or Stille reactions. We have established a methodology for [1,5]-electrocyclization using chiral phase-transfer catalysis. These reactions afford the electrocyclized products in excellent yield and diastereoselectivity with enantiomeric excess up to 68%. These transformations offer a glimpse of the potential of electrocyclic reactions. In chapter 2, the effects of cyclic backbones on the secondary structures of γ-peptides were evaluated. Two series of abiotic γ-peptides were synthesized with five and six-membered cyclic backbones. We have demonstrated that intra-residue nearest-neighbour hydrogen bonds may be favoured when the flexibility of the ring constraint can permit their formation. These cyclic backbone containing γ-peptides have been shown to populate a bend-ribbon conformation in the solution and solid phase by NMR and X-ray crystallography respectively.

Pericyclic reactions are a class of transformations that comprise sigmatropic rearrangements, group transfer reactions, cycloadditions and electrocyclic reactions. Since Woodward and Hoffmann rationalized the mechanism and stereochemistry of pericyclic reactions they have become powerful synthetic tools. Whilst sigmatropic rearrangements and cycloadditions are cornerstones of contemporary synthetic methodology, many electrocyclic reactions are not fully exploited currently; there are no general methods for the asymmetric catalysis of electrocyclic reactions and as a consequence, opportunities for exerting stereocontrol in these manifolds are limited. We aim to establish general methods for the asymmetric catalysis of 6π electrocyclic reactions. Our initial studies are focused on a pentadienyl anion moiety due to the greater ease of cyclization observed with such systems in comparison to the corresponding neutral hexatriene systems.

¤@¡BFlash vacuum pyrolysis (FVP) of 2-dimethylaminostilbene and its derivatives via elimination of methyl radical followed by cyclization gave quinoline and 1-methylindole and 3-phenylquinoline and 3-phenylindole. On the other hand, Photolysis of 2-dimethylaminostilbene and its derivatives via electrocyclization gave 1-dimethylaminophenanthrene, phenanthrene, 2-(4-methoxy-phenyl)-1-methyl-1H- quinolin-4-one and 1-methyl-1H-indol-2-yl)phenylmethanone. Photolysis of 2,4'-dimethoxystilbene in acidic sulotion gave 1,6-dimethoxypheanthrene and 1-methoxypheanthrene and ketone compound via electrocyclization followed by [1,9] hydrogen shift. ¤G¡BFVP of 2-(2-chlorostyryl)pyridine gave benzo[f]quinolin, benzo[h]quinolin, on the other hand, FVP of 4-(2-chlorostyryl)pyridine gave different benzo[h]quinolin.

1-(o-(Dimethylamino)phenyl)-3-phenylprop-2-en-1-one (62), 3-(o-(dimethylamino)phenyl)-1-phenylpropenone (63) and 1-(o-(dimethyl- amino)phenyl)-3-phenylprop-2-yn-1-one (64) were synthesized and their pyrolytic and photolytic chemistry were studied. Flash vacuum pyrolysis (FVP) of 62 and 64 gave 11H-benzo[a]carbazole (72) and benzo[c]carba-zole (73), FVP of 63 gave phenanthrene (2) and 1-methylquinolin-2(1H)-one (84). Under photolytic conditions, 62 and 64 gave the expected photocyclic products 1-methyl-2-phenylquinolin-4-one (65), while 63 gave the expected photocyclic products (1-methyl-1H-indol-2-yl)phenyl-methanone (66).

Flash vacuum pyrolysis of 2-(2-vinylstyryl)furan derivatives via electrocyclization followed by dehydrogenation will give 2-(2-naphthalen-2-yl)furan analogues, on the other hand, FVP of 2-(2-vinylstyryl)furan derivatives via electrocyclization followed by [1,5]-H shift will give 3-(2-furyl)-1,2-dihydronaphthalene analogues. FVP of 2-[2-(4-methoxyphenyl)vinyl]benzo[b]thiophene gave three products: trans-4-(2-benzo[b]thiophen-2-ylvinyl)phenol, benzo[b]naphtha[1,2-d]thiophen-2-ol and 1H-6-thiacyclopenta[c]fluorene.

Ces travaux de thèse ont permis de développer une voie d’accès à des systèmes polycycliques complexes contenant un cyclooctatétraène par réactions en cascade palladocatalysées à partir de substrats de départ originaux. Le mécanisme de formation de ces composés est tout à fait particulier. Une étude mécanistique approfondie, corroborée notamment par des calculs DFT, a mis en avant une étape de réaction inédite : une électrocyclisation conrotatoire 8pi d’un système triènyne formant ainsi un cyclooctadiènallène palladé. Cette méthodologie a permis de synthétiser de nombreux cyclooctatétraènes présentant une large diversité moléculaire. Les différents substituants du cyclooctatétraène ont pu être variés ainsi que la taille des cycles fusionnés à ce cyclooctatétraène. / This thesis work focused on the development of a new synthetic pathway leading to complex polycyclic molecules containing a cyclooctatetraene moiety via palladium-catalyzed cascade reactions from original starting substrates. The mechanism of formation of these compounds is very special. A thorough mechanistic study, supported in particular by DFT calculations, highlighted an unprecedented reaction step: an conrotatory 8pi electrocyclization of a trienyne system forming a palladiated cyclooctadienallene. This methodology allowed the synthesis of many cyclooctatetraenes showing a broad molecular diversity. The different substituents bearing by the cyclooctatetraene core were varied as well as the size of the fused rings to the cyclooctatetraene.

No description available.

Recently, considerable interest has been devoted to the synthesis of new ferrocene derivatives since properly functionalized ferrocene derivatives could be potential antitumor substances. For this purpose, we have investigated the synthesis of ferrocenyl quinones starting from squaric acid. Thermolysis of ferrocenylsubstituted cyclobutenones, which have been prepared from ferrocenyl cyclobutenediones and alkenyllithiums, affords hydroquinones, which furnish, upon oxidation, ferrocenyl quinones. Ferrocenyl cyclobutenediones have been prepared from known cyclobutenediones by nucleophilic addition of ferrocenyllithiumfollowed by hydrolysis, Pd/Cu-cocatalyzed cross-coupling with (tri-n-butylstannyl)ferrocene or Friedel&amp / #8211 / Crafts alkylation with ferrocene. A mechanism involving electrocyclic ring opening of alkenyl substituted cyclobutenone to dienylketene and consequent electrocyclic ring closure to cyclohexadienone followed by enolization has been proposed to account for the formation of ferocenyl substituted hydroquinones. Rocket design and production is one of the hottest topics in defense industry. On this subject, significant amount of investments have been done and excellent results were obtained. Among the burning rate catalysts for composite rocket propellants, ferrocene derivatives are one of the most famous ones. Although ferrocene derivatives are superior to some other burning rate catalysts, their use has some drawbacks arising from the tendency of migration in the bulk of the material and their sensitivity toward oxidation by air. With the aim of preventing the negative aspects of ferrocene derivatives, we have investigated the synthesis of EDA (ethylenediamine), TEP (tetraethylenepentamine) and DDI (dimeryl-diisocyanate) based ferrocene derivatives.

SYNTHESIS OF FERROCENYLIDENE CYCLOPENTENEDIONES K&ouml / kt&uuml / rk, Mustafa M.S., Department of Chemistry Supervisor: Assoc. Prof. Dr. Metin Zora August 2005, 83 pages 2-Arylidine-4-cyclopentene-1,3-diones are known to be antitumor agents. Incorporation of the essential structures of such compounds with a ferrocene moiety instead of an aryl group could provide subtances with enhanced antitumor activities since some ferrocene derivatives have already proved to be active against a number of tumors. Thus, we have investigated the squarate-based synthesis of 2-ferrocenylidene-4-cyclopentene-1,3-diones. Upon thermolysis, 4-hydroxy-4-ferrocenylethynyl-2-cyclobutenones, prepared from 3-cyclobutene-1,2-diones and lithioethynylferrocene, produced exclusively 2-ferrocenylidene-4-cyclopentene-1,3-diones. In some cases, ferrocenyl quinone derivatives are obtained in very minor amounts. Moreover, the heating of a mixture of 4-ferrocenylethynyl-4-hydroxy-2-cyclobutenones and silica gel in oven at 120 oC without using any solvent provided the same type of products. More importantly, the stirring of a solution of 4-ferrocenylethynyl-4-hydroxy-2-cyclobutenone (37A-C) derivatives in ethyl acetate at the room temperature yielded the same type products, as well. It appears that 4-hydroxy-4-ferrocenylethynyl-2-cyclobutenones are more reactive than corresponding phenyl analogs. For the formation of ferrocenyl-substituted cyclopentenediones, a mechanism involving first electrocyclic ring opening of ferrocenylethynyl-substituted cyclobutenones to corresponding ketene intermediate and then ring closure, has been proposed. The exclusive formation of cyclopentenediones is attributed to the radical stabilizing ability of the ferrocenyl moiety during the course of the reaction.

ABSTRACT SYNTHESIS OF FERROCENYL QUINONES AND POLYQUINANES Eralp, Tug&ccedil / e M.S., Department of Chemistry Supervisor: Assoc. Prof. Dr. Metin Zora June 2005, 79 pages With the discovery of antitumor activity of ferrocene derivatives, research on new ferrocene derivatives have gained importance. For this purpose, we have investigated the synthesis of ferrocenyl quinones starting from squaric acid. Several quinone derivatives are known to have antitumor and antibiotic activities. In this research, by combining ferrocene and quinone moieties, we have targeted ferrocenyl quinones which are supposed to have enhanced potential antitumor activity. Thermolysis of ferrocenyl-substituted 4-alkynyl cyclobutenones, which have been prepared from ferrocenyl cyclobutenediones and alkynyllithiums, leads to the formation of ferrocenyl quinones and besides also cyclopentendiones are observed. Ferrocenyl cyclobutenediones have been prepared from known cyclobutenediones by nucleophilic addition of ferrocenyllithium followed by hydrolysis. A mechanism for the formation of ferrocenyl substituted quinones, involving first electrocyclic ring opening of alkynyl substituted cyclobutenone to ketene intermediate and then ring closure, has been proposed. Polyquinanes are widely found in nature and proved to have biological activity such as antibiotic activity. For the synthesis of ferrocenyl polyquinanes, starting from squaric acid, ferrocenyl substituted cyclobutenediones were prepared and reacted with alkenyllithium, and hydrolyzed to afford ferrocenyl substituted polyquinanes. A mechanism has been proposed that involves first the formation of cis- and trans-divinyl substituted cyclobutenes that produce cyclooctatriene-dienolate, upon hydrolysis of this dienolate, aldol-type transannular ring closure reaction takes place, producing polyquinanes.