Cristallographie aux rayons X | EPFL Graph Search

La cristallographie aux rayons X, radiocristallographie ou diffractométrie de rayons X (DRX, on utilise aussi souvent l'abréviation anglaise XRD pour X-ray diffraction) est une technique d'analyse fondée sur la diffraction des rayons X par la matière, particulièrement quand celle-ci est cristalline. La diffraction des rayons X est une diffusion élastique, c'est-à-dire sans perte d'énergie des photons (longueurs d'onde inchangées), qui donne lieu à des interférences d'autant plus marquées que la matière est ordonnée. Pour les matériaux non cristallins, on parle plutôt de diffusion. Cette méthode utilise un faisceau de rayons X qui, rencontrant un cristal, est renvoyé dans des directions spécifiques déterminées par la longueur d'onde des rayons X et par les dimensions et l'orientation du réseau cristallin. Par la mesure des angles et de l'intensité des rayons diffractés, il est possible d'obtenir les dimensions de la maille cristalline, les symétries de la structure cristalline (grou

Copper-Catalyzed 1,2-Methoxy Methoxycarbonylation of Alkenes with Methyl Formate and Synthetic Studies Towards the Total Synthesis of Koumine, Voacafricine A and Voacafricine B

Balázs Budai

The development of an unusual oxidative alkene difunctionalization using methyl formate and syn-thetic studies towards alkaloid natural products provide the basis of the thesis. The first chapter details the development of a method that forges methoxycarbonyl radical direct-ly from its most accessible precursor: methyl formate. Although the aforementioned transfor-mation was documented in the literature, no synthetically useful method was developed at the time. We were able to identify conditions that transform methyl formate and simple styrene de-rivatives to value added ï¢-methoxy alkanoates and cinnamic acid derivatives under copper cataly-sis. We also demonstrated that by tethering nucleophilic moieties to the styrene substrates, we could access medicinally important heterocycles such as pyrrolidines, tetrahydrofurans and ï§-lactones. Our method proved to be scalable on each classes of substrates. Mechanistic studies re-vealed that methyl formate has an unprecedented double role in the transformation. It acts as a precursor for methoxycarbonyl radical; furthermore, it is the direct source of the ï¢-methoxy func-tion in the synthesis of ï¢-methoxy alkanoates. A ternary ï¢-diketiminato-Cu(I)-styrene complex, fully characterized by NMR spectroscopy and X-ray crystallographic analysis is capable of catalyz-ing the same transformation. We hypothesize that pre-coordination of electron-rich double bond to copper might play an important role in the polarity-mismatched addition between nucleophilic methoxycarbonyl radical and electron rich olefins. Synthetic studies toward the total synthesis of koumine is discussed in the second chapter. Our synthetic strategy features an oxidative ring closing, Fukuyama indole synthesis and an enantiose-lective Diels-Alder cycloaddition for the construction of the core of koumine skeleton. We designed a rapid route to access 1,2-dihydropyridine derivatives and these compounds were examined as dienes in the Diels-Alder cycloaddition reaction. Despite our efforts, we were unable to effect the [4+2] cycloaddition, which eventually lead us to decide to discontinue our campaign. In chapter three, our synthetic efforts toward voacafricine A and voacafricine B is presented. In our pursuit towards the natural products, we devised and followed a divergent and potentially en-antioselective strategy. We successfully developed a synthetic route to reach the key intermediate in five steps. Despite our efforts, we were not able to construct the remaining F ring of the natural product. Our conformational analysis of advanced intermediates suggest that epimerization of the C14 stereocenter potentially unlocks the desired reactivity and enables us to reach the target mol-ecules. Work towards the total synthesis of voacafricine A and voacafricine B is underway and may focus on the conformational manipulation of advanced intermediates to allow the elaboration of the F ring and complete the synthesis.

EPFL2020

Simulations d'une structure cristalline incommensurable à caractère désordonné

Eric Germaneau

Incommensurate crystal structures do not display three-dimensional periodicity. Discovered in the 1960's, a mathematical model has been established in 1974 only. Incommensurate structures belong to the big family of aperiodic structures. The modulation of incommensurate structures manifests itself as satellite reflections around the main peaks on X-rays diffractograms. Short range order correlations in crystals lead to diffuse scattering between Bragg peaks in the diffraction pattern. The computing power available today allows for very time consuming simulations of the incommensurate or disordered crystal structures. Simulations based on Monte-Carlo and the molecular dynamic techniques have been performed. The former is based on stochastic algorithms, whereas the latter is deterministic. This PhD thesis strove to combine these two methods, using a four-isomermodel, in order to study the incommensurate, disordered polymorph of p-azoxydiphenetol (PAP), which crystallises below 356 K. One of the main features of the PAP molecule is its dative bond. A Monte-Carlo program, using true empirical potentials, has been developed in order to explain the behaviour of PAP. This code (6000 lines), written in C, uses the GSL and OpenMP libraries. Using numerical and experimental tools, this thesis provides explanations for the origin, from an atomic point of view, of the incommensurate and disordered behaviour of PAP. Calculations have been performed on the clusters of École Polytechnique Fédérale de Lausanne. Simulated diffraction patterns have been compared to experimental data, collected before and during this study. Moreover, a set of differential scanning calorimetry (DSC) measurements has been carried out during this work, the results of which have been analysed based on Arrhenius's law. For a better understanding of the role played by the dative bond, and the relation between the complexity of the molecule and the structure, DFT and ab initio calculations have been performed. This work has successfully woven the results from different experimental and numerical techniques into a comprehensive model for this very complex system indeed.

EPFL2008