Tröndlin, Lars. Entwicklung neuer P,N-Liganden und ihre Anwendungen in der Iridium-katalysierten Hydrierung von α,β-ungesättigten Carbonsäureestern. 2011, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_9788
Catalyst development. Two novel families of iridium P,N-complexes have been prepared and tested in the context of Ir-catalyzed asymmetric hydrogenation. The first class of P,N-ligands synthesized featured modification at the phosphorus unit, and allowed for the preparation of a series of twelve different pyridinyl-phosphinites Ir-catalysts, combining R,R- and S,S-diphenylethylenediamine with different chiral pyridinyl-alcohols. These complexes were evaluated as catalysts in the hydrogenation of a series of unfunctionalized and functionalized alkenes, especially alpha, beta-unsaturated esters. The hydrogenations of several unfunctionalized and functionalized alkenes were very effective, affording ee values up to 99%. A study on alpha-methylated alpha, beta-unsaturated esters with different substituents at the beta�position gave ee values above 90%. The new iridium complexes were also tested in the hydrogenations of beta-methylated carboxylic acid esters, affording ee values above 95%.
The design and synthesis of new imidazoline based P,N-ligands was next studied. Although structurally very similar to oxazoline ligands, an additional nitrogen atom provided a useful handle for tuning the electronic and conformational properties of the ligand by proper choice of the group bound to nitrogen. An efficient synthetic route was found for the preparation of the imidazoline based iridium-complexes. The conversions and ee values observed thus far with this new family of catalysts were unsatisfactory.
However, fine tuning of the electronic and steric properties of this ligand family was possible via modification of the substituents at the nitrogen atom. Specifically, we envisioned that replacement of the aromatic ring with a sulfonyl group might be effective. We were able to successfully prepare and test four new sulfonyl-imidazoline based catalysts, which enabled the hydrogenation of several unfunctionalized and functionalized alkenes with levels of asymmetric inductions above 90%.
Application in the synthesis of Platensimycin and Aliskiren. As a second part of this thesis, applications of Ir-catalyzed asymmetric hydrogenations towards the preparation of biologically important natural products and pharmaceuticals were pursued. Within the frame of a collaboration with Prof. J. Mulzer (University of Vienna, Austria), an asymmetric synthesis of Platensimycin was envisioned. The planned synthetic route included the asymmetric hydrogenation of two key intermediates which was achieved with excellent conversions and levels of asymmetric induction using catalyst 67c, developed in the first part of this doctoral thesis. Notably, this iridium-complex allowed for very low catalyst loadings and multigram scale reactions.
The next synthetic project tackled was the synthesis of Aliskiren. In this context, several different analogues of ester were prepared and tested under iridium-catalyzed asymmetric hydrogenation conditions. After extensive catalyst screening, the desired tert-butyl ester was obtained with full conversion and 99% ee using PHOX complex 28a or PHIM complex 134a.
|Committee Members:||Wennemers, Helma|
|Faculties and Departments:||05 Faculty of Science > Departement Chemie > Chemie > Synthetische organische Chemie (Pfaltz)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||357 S.|
|Last Modified:||30 Jun 2016 10:42|
|Deposited On:||13 Mar 2012 15:45|
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