Approche combinatoire au développement de structures chirales tridentes pour les complexes de métaux de transition présentant un environnement plan carré – COMBITRIDE

Research oriented towards the design of new tools enabling the creation of stereogenic centers with high degrees of selectivity through environmentally friendly methodologies constitutes a major objective of both academic and industrial chemists. Metal catalyzed enantioselective homogeneous catalysis represents a field of choice for the development of highly efficient cost-effective synthetic transformations. This project propose a new approach to the design of chiral group 10 Lewis acids possessing a single empty coordination site. These dicationic complexes offer the possibility to activate electrophilic substrates coordinated to the metal via a single point attachment. The possibility to place ligands in cis position to the substrate allows achieving a high level of enantiocontrol of the catalytic transformation. Recent studies, reported both in our group and by colleagues, demonstrated the possibility to mimick the tridentate scaffold around the metal center through the use of a in situ prepared combination of one bidentate and one monodentate ligand. Our study deals with the possibility to form in a simple and efficient way and directly evaluate in catalysis libraries of combinatorial chiral tridentate complexes from libraries of synthetically or commercially readily available ligands. The large spectrum of stereoelectronic properties accessible by this approach should allow the development and optimization of new, substrate-sensitive enantioselective transformations. The first step of the proposal deals with the formation of the libraries of complexes and their caracterization using spectroscopic methods. A specific emphasis will be brought to the purity of the formed species and the reproducibility of the synthetic methods. From a technical point of view, methodologies favouring the use simple handling techniques and already available caracterization techniques in order to limit the cost and avoid time-wasting optimizations. Tasks 2 to 4 will be conducted independantly and represent three types of reactions where the libraries of group 10 Lewis acids will be investigated to tackle selectivity issues. Cycloisomerization reactions catalyzed by carbophilic late transition metals Lewis acids, especially platinum or gold, have exhibited a substantial growth of interest over the last decade. Until now, asymmetric variants of these transformations have been scarcely studied and presented a high degree of substrate dependance. Imine and carbonyl electrophilic allylation reactions in the presence of organometallic reagents have been described in the presence of Ni-, Pd- and Pt-catalysts. Enantioselective variants often rely on the use of difficultly accessible ligands and induce moderate enantioselectivities. The ene carbonyl reaction is the subject of intensive attention due to the almost perfect level of atom economy generated during the direct coupling process of a carbonyl group and an allyl fragment. So far, this reaction has been limited to a narrow spectrum of substrates. The higher reactivity associated with the use of dicationic complexes and the control of the substrate coordination mode via a single point attachment to the metal center should allow the extension of this transformation to other classes of substrates and to develop more efficient asymmetric variants. We are offering to apply the libraries of complexes obtained in our initial research phase to the optimization of asymmetric versions of the aforementionned catalytic transformations. This research proposal is supported by the experience of the participants in ligand and complex design, homogeneous catalysis, especially enantioselective catalysis, and combinatorial methods applied to the optimization of catalytic reactions. This project is also backed up by highly encouraging preliminary results, presents a good interface with the current research programs conducted in our group and is expected to introduce new methods to increase the chemical know-how of our research unit.