Study of chiral iridium N,P ligand complexes as catalysts for the asymmetric hydrogenation of different substrate classes

Abstract

The objective of this thesis was the synthesis and further development of different iridium N,P ligand complexes as well as the evaluation and application of different challenging substrate classes in the asymmetric hydrogenation using iridium-based catalysts. The first chapter of this thesis deals with the further development of bicyclic pyridine-based ligands. A late stage Suzuki?Miyaura cross-coupling allowed for the synthesis of a large variety of different ligands for which a phenyl group was exchanged with more sterically demanding aryl-group. Iridium complexes of these new ligands emerged as efficient catalysts for the asymmetric hydrogenation of different functionalized and unfunctionalized olefins. For several substrate classes superior results were achieved compared to the original catalysts. Significant improvements were achieved with a,s-unsaturated esters which were hydrogenated with high conversion and excellent enantioselectivity. In cooperation with DSM Nutritional Products different tocopherol side chain precursors were investigated as substrates for the asymmetric hydrogenation using these new catalysts. Hydrogenations of (5E,9E)-farnesylacetone resulted in the reduction of three C=C bonds, the introduction of two new stereogenic centers and the almost exclusive formation of the desired stereoisomers in combination with high catalyst reactivity. Another substrate class which was investigated in the course of this PhD thesis are vinyl bromides. Established iridium-based catalysts turned out to be extremely unreactive in the hydrogenation of this substrate class. Only terminal vinyl bromides revealed a certain reactivity. The sixth chapter of this thesis addressed the hydrogenation of a,s-unsaturated nitriles using iridium-based catalysts. Although, first experiments revealed that iridium-based catalysts were inhibited by a,s-unsaturated nitriles it was found that they become highly active catalysts upon addition of N,N-diisopropylethylamine. The base-activated catalysts enable conjugate reduction of a,s-unsaturated nitriles with H2 at low catalyst loadings, affording the corresponding saturated nitriles with high conversion and excellent enantioselectivity. In contrast, alkenes lacking a conjugated cyano group do not react under these conditions, making it possible to selectively reduce the conjugated C=C bond of an a,s-unsaturated nitrile, while leaving other types of C=C bonds in the molecule intact. In the last chapter of the thesis new experimental data gained on the behavior of iridium N,P ligand complexes in the absence of substrate were used to develop an efficient protocol for the recovery of N,P ligand complexes. Upon addition of COD after the hydrogenation reaction it was possible to recover up to 70% of the catalyst. The recovered catalysts gave similar conversions and the same enantiomeric excesses as the original catalysts.