Application de la chimie radicalaire par Xanthates: Synthèse des composés hétéroaromatiques

Abstract : In this thesis we are interested in the synthesis of nitrogen-containing heterocyclic derivatives, which are based on benzazepinones, pyridines and pyrimidines. These works are carried out under the supervision of Prof. Samir Z. Zard in Laboratory of Organic Synthesis in Ecole Polytechnique. This manuscript consists of five chapters. At first, we will briefly present the main principles of radical chemistry (Chapter I), and then especially the xanthate chemistry which was developed in the laboratory (Chapter II). The purpose of these chapters is to present the general conceptions of radical chemistry as well as some conventional radical methods, to familiarize the reader with the radical xanthate transfer chemistry. In Chapter III, we will describe a novel synthesis of benzazepin-2- ones and 5-aryl-2-piperidones using xanthate transfer technique from simple starting materials, via radical cyclization to aromatic ring in a 7-endo-trig manner. Optimized conditions of the ring closure step afford moderate to excellent yields for this synthesis. Moreover, the presence of halogen atoms in the aryl group of the products makes it possible to combine this radical process with some other powerful transition metal catalyzed reactions, which could have interesting pharmacological applications. In Chapter IV, 3,4-disubstituted-5,6-difluoro-7-azaindoles and 7-azaindolines are prepared in good yield starting from the commercially available pentafluoropyridine. The formation of these two compounds includes the homolytic rupture of a very strong C-F bond, which is very rare in such mild conditions. The efficiency of this intramolecular radical cyclization is found to be very sensitive to the electronic property of the C-4 substitution. Based on this work, a mini-library of various compounds of 7-azaindolines and 7-azaindoles could be generated. In Chapter V, a direct route to novel polycyclic aza-pyrimidine structures, including 5-, 6-, 7-membered rings, is described involving radical addition and cyclization of xanthates. One of the main developments in this work is the possibility of using substrates which are unprotected at the non-aromatic nitrogen. The methodology could be partially extended to pyridine series. Furthermore, the first radical cyclization to heteroaromatic nitrogen in a 6-endo-trig manner was also realized. The development of these syntheses provided better understanding of some reaction mechanisms as well as to discover new processes.
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Zhibo Liu. Application de la chimie radicalaire par Xanthates: Synthèse des composés hétéroaromatiques. Chimie organique. Ecole Polytechnique X, 2014. Français. ⟨pastel-00980912⟩

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