Hydroamination intermoléculaire des oléfines non activées : vers la compréhension du mécanisme et le développement d’une version asymétrique – HYDROAM

The catalyzed intermolecular hydroamination of alkenes and more specifically its enantioselective version is nowadays a scientific and economic challenge. Concerning the activated alkenes, the area is still little developed and applications to the synthesis of products (chiral amines) of high commercial values have not yet been reported. In the non-activated alkenes (simple olefins) version, in spite of much effort, no satisfactory results have been achieved yet. We have discovered the first catalytic systems really efficient for this type of reaction, made up from the association of Pt(II), Pt(IV) or Rh(III) salts with phosphonium halides (n-Bu4PX). These are the most performing systems ever reported for the hydroamination of ethylene by weakly basic amines and the only ones allowing the hydroamination of higher olefins. Moreover, the high regioselectivity (95 %) obtained, is favourable for the development of an enantioselective version, which remains an unexplored area of research. We have a triple objective: (a) Arrive at a complete understanding of how the two simple metal systems recently developed in our laboratory operate, by the isolation of intermediates of the catalytic cycles, mechanistic studies, and computational studies. With such knowledge in hand we will be able to design new generation catalytic systems that meet with the requirements of efficient large scale production. (b) Develop the intermolecular enantioselective hydroamination with two independent goals: to find catalytic systems of general applicability for the hydroamination of activated alkenes in order to accomplish efficient syntheses of high added value chiral amines; to accomplish the asymmetric hydroamination of non activated olefins. Ligands already existing in the two participating laboratories have the potential of yielding the first successful demonstration of feasibility. Simple modifications of the ligand environment will subsequently be guided by the acquired knowledge of the key transition state (previous objective) and by QM/MM or full QM calculations. (c) Adapt the experimental conditions in such a way that the catalyst can be efficiently separated from the reaction products, recovered and recycled without significant leaching or decomposition. This objective may also be achieved through ligand modification.