Academic literature on the topic 'Dieckmann cyclisation'

Novel routes for the synthesis of spiro derivatives anthrone have been designed using a Michael addition reaction followed by a Dieckmann condensation and Thorpe–Ziegler cyclisation. Bis-Michael addition of pyrazole-5-thione with 1,5-diarylpenta-1,4-dien-3-one gave directly a spiro derivative of pyrazole-5-thione. An enol lactone was synthesised by using mono Michael addition on dimedone, followed by hydrolysis and condensation.

Polypropionate marine natural products have emerged as a class of compounds that display a high degree of structural diversity. Specifically, metabolites such as that reported as tridachiahydropyrone (7), isolated from sacoglossan molluscs, display novel ring systems. The introductory chapter gives some background on tridachione marine natural products and outlines the isolation of metabolites from several species of sacoglossan mollusc. Chapter One also gives examples of the utility of the tandem conjugate addition-Dieckmann condensation approach being applied to the synthesis of these compounds. Chapter Two describes the development of the tandem conjugate addition-Dieckmann condensation and subsequent trans methylation approach to cyclohexenone rings. The synthetic strategy utilised chiral, functionalised cyclohexenone rings as synthons in the formation of bicyclic ring systems, so development of the carbocyclic ring formation was of vital importance to the overall strategy. Examples are given which confirm the viability of the proposed synthetic route to cyclohexenones such as 91, 92 and 104 from the reaction of [alpha,beta]-unsaturated carbonyl compounds 39 and 59 with dialkyl and dialkenyl Gilman cuprates. Chapter Three describes the incorporation of chiral cyclohexenone 117 into the bicyclic framework of model compound 105, analogous to the marine natural product reported as tridachiahydropyrone (7). The chapter explores the use of cyclohexenone precursor 43 that contained the total carbon framework of the bicyclic core of the desired pyrone. Once again, a tandem conjugate addition-cyclisation reaction was employed using a dialkyl Gilman cuprate, followed by trans methylation to give the requisite cyclohexenone synthon 117. A novel Eaton’s reagent-promoted intramolecular cyclisation of acid 122 to pyrone 123 was then effected. Subsequent O-methylation afforded [alpha]-methoxy-[beta]-methyl-[gamma]-pyrone 105 as a single enantiomer, which had the identical core structure to the natural product. The structure, including relative stereochemistry of 105, was confirmed by single crystal X-ray analysis. Chapter Four builds on the previous two chapters and describes the conjugate addition-cyclisation with a higher order Gilman cuprate derived from vinyl bromide 44, which would deliver the vinyl side-chain required for the synthesis of reported natural product 7. The same acyclic precursor 43 as used in Chapter Three was cyclised and methylated to yield yet another cyclohexenone synthon 41. A single crystal X-ray analysis of related alcohol 162 confirmed the relative stereochemistry and structure. Another novel P2O5-mediated intramolecular cyclisation was achieved to give pyrone 168 and O-methylation provided a compound with the reported structure of natural product 7 as a single enantiomer. The structure of synthetic 7 was established unequivocally through extensive NMR studies. Comparisons of spectral data confirmed that natural tridachiahydropyrone was not the same as synthetic compound 7, so revision of the assigned natural product structure is warranted. Several other analogues were also synthesised using this methodology, highlighting the versatility of the method under development.

Dans le cadre d'une nouvelle thématique de recherche développée dans notre laboratoire, nous avons étudié la réactivité d’amides α-bromés dans des réactions tandem. Pour cela deux stratégies différentes ont été investiguées pour atteindre des structures tri-, tétra-, et pentacycliques d'alcaloïdes de la famille des spiro [pyrrolidin-3,3’-oxindoles] reconnues pour leurs potentialités cytotoxiques et anticancéreuses. Le premier chapitre bibliographique a été l’occasion de présenter la maladie « cancer » tout en replaçant dans son contexte la chimiothérapie dans les traitements les plus efficaces actuellement. Ainsi, au coeur des motifs les plus intéressants et les plus étudiés sont les dérivés spiro oxindoliques qui sont les cibles principales de cette thèse. Nous avons exploré dans le deuxième chapitre une première séquence tandem de type substitution électrophile/addition nucléophile intramoléculaire avec pour but la construction de tels squelettes contenants un noyau oxindole spiro-fusionné avec le motif succinimide. Ce dernier motif constitue l’atout majeur de cette séquence car par réduction sélective de l’un des deux groupes carbonyles du noyau succinimide nous avons eu accès à des α-hydroxy-γ-lactames précurseurs d’ions N-acyliminiums en milieu acide. Ainsi, en générant les espèces ioniques correspondantes par action d’un acide de Lewis ou de Bronsted nous avons mis à profit des réactions de p-cyclisations cationiques intramoléculaires pour accéder essentiellement à des structures spiraniques pentacycliques. Le troisième et dernier chapitre développe une seconde séquence tandem originale de type addition Aza-Michael/substitution nucléophile intramoléculaire pour former des systèmes possédants cette fois-ci un noyau oxindole spiro-fusionné avec le motif γ-lactame. La grande variété des structures accessibles par cette approche ouvre l’accès à plusieurs applications synthétiques dont des réactions de cyclisation intramoléculaire pour atteindre des structures plus élaborées. Ainsi des réactions de type Friedel-Crafts et Dieckmann ont été mises à profit pour atteindre des dérivés tétra- et pentacycliques considérés comme des analogues proches de nombreux alcaloïdes spiranniques modèles
Our contribution for the synthesis of spiro-oxindole templates is presented in this memory. For that purpose we have investigated two different approaches employing N-substituted α-bromoacetamides in tandem processes. In the first chapter we have highlighted the importance of chemotherapy in the treatment of disease such as cancer. Among the efficient molecules discovered, the unique structure of the spiro oxindole framework has encouraged the creativity of many researchers. In the second chapter our work was focused on the development of a tandem process to allow the access to oxindoles spiro-fused with succinimide ring. α-Hydroxy-γ-lactams were obtained by regio- and stereoselective reduction of one of both carbonyls of the succinimide moiety and were then engaged in π-cationic cyclization reactions via N-acyliminium species generated by Lewis or Bronsted acids. Thus, complex pentacyclic spiro oxindoles molecules were isolated in good yields and high diastereoselectivities. The third chapter was centered on the application of a new tandem reaction developed in our Laboratory for the synthesis of oxindoles spiro-fused with γ-lactams. The wide variety of reachable structures employing this strategy should allow us to obtain in the near future numerous spiro oxindole frameworks depending on the chemistry involved. Already, Friedel-Crafts and Dieckmann cyclizations were shown to be efficient for the synthesis of elaborated tetra- and pentacyclics spiro oxindole systems, which could be considered as analogous to numerous spiro alkaloids models