Chiral dialkenes for resolution of stereolabile ligands

Molecular chirality ("handedness") is a characteristic feature of many biologically active compounds and the two enantiomers of a chiral compound can exhibit very different characteristics. Nevertheless, even in the early 1990s about 90 % of synthetic chiral drugs were still racemic, which means that they consisted of both enantiomers in equimolar amounts. Thus, gaining a synthetic access to these natural products in enantiopure form is of enormous importance for the development of pharmaceuticals, agrochemicals, and flavours. The development of efficient asymmetric catalysis for organic reactions that allow the synthesis of such compounds is still a challenge in modern synthetic chemistry. In chemical systems, asymmetric catalysis is commonly achieved by the use of (transition)metal complexes that contain chiral organic ligands. The use of atropisomeric biaryl donor ligands as chiral organic ligands is ubiquitous. In a more recent approach, these atropisomeric ligands are replaced by related stereolabile ligands that can be fixed in one chiral configuration in situ in the presence of a chiral metal fragment ("in situ resolution of stereolabile ligands"). The aim of this proposal is to develop a new strategy for the in situ resolution of stereolabile ligands upon forming directly the catalytically active chiral catalyst. For this purpose, a chiral chelating dialkene should be prepared in enantiopure form. Corresponding rhodium or iridium complexes, respectively bearing this chiral dialkene as a ligand should then be utilised to fix stereolabile biaryl donor ligands into one fixed configuration and form the active catalyst upon complexation. With this modular approach it should be possible to synthesise a variety of new chiral catalysts. The focus of interest will involve the resolution of stereolabile biaryl ligands containing nitrogen and phosphorus as the donor atoms. The catalytic activity of these new chiral catalysts would then be studied in detail. One emphasis in catalysis would be in developing new strategies in rhodium catalysed hydroboration, especially for less reactive alkenes. Further emphasis lies in iridium-catalysed asymmetric hydrogenation of alkenes and alkynes to reveal new stereogenic centres. This would offer new possibilities in the synthesis of various natural products.