Supported Titanocenes for the Heterogeneous Hydrosilylation of Imines

Chiral reductions using transition metal complexes are one of the largest sub-classes of chiral reactions carried out on an industrial scale. In this context, hydrosilylations have gained considerable importance during the last years, since these reactions can be carried our under mild and controlled conditions. However, hydrosilylations are mostly carried out using homogeneous catalysts that lack the advantages of their heterogeneous counterparts, such as easy separation and re-use of the catalysts, removal of the active metal, and long-term stability.

We present novel catalytic systems for the heterogeneous hydrosilylation of imines employing supported titanocenes. In the first step we synthesized tethered titanium compounds, which include ligands of different length and functionality. The synthesis and optimization of the new catalysts were accompanied with molecular modeling approaches using Density Functional Theory methods in order to investigate (a) the relationship between function and structure of the catalysts [1] and (b) possible transition states of the catalytic active compounds [2]. The tethered titanocenes were then covalently immobilized on various solid supports including H-terminated Si-wafers [3], H-terminated Si-particles as well as on functionalized silica gel particles. Employing the heterogeneous catalysts for the hydrosilylation of imines, they proved to be highly active and selective. The products of these reactions are chiral amines, which can be found in more than 85% of all active pharmaceutical ingredients. Thus, implementation of the novel heterogeneous catalysts in continous reaction set-ups may be a step towards the realization of continuous bulk drug manufacturing.

[1] Gruber-Woelfler, H.; Flock, M.; Saßmannshausen, J.; Khinast, J. Organometallics, 2008, 27, 5196-5202 [2] Gruber-Woelfler, H., Flock, M.; Fischer, R. C.; Saßmannshausen, J.; Stanoeva, T.; Gescheidt, G.; Khinast, J., Organometallics, 2009, 2546-2553 [3] Gruber-Woelfler, H.; Rivillon, S.; Chabal, Y. J.; Polo, E.; Ringwald, M.; Schitter G., Khinast, J., Chem. Commun., 2008, 1329-1331