ASYMMETRIC HYDROGENATION OFINDUSTRIALLY RELEVANT SUBSTRATES

This thesis is divided in two parts: In Part A (Chapters I to III), the studies on the asymmetric hydrogenation of substituted pyridines are described. These heteroaromatic compounds have proven very challenging to hydrogenate enantioselectively, however, the resulting chiral piperidines are of high industrial interest. In Chapter I, the state of the art and the mechanistic studies carried out on related N-heteroaromatic substrates are extensively discussed. In Chapter II, a new method for the asymmetric hydrogenation of 2-substitued pyridines is reported, together with complementary mechanistic studies that shed light on the origin of the enantioselectivity. In Chapter III, a method for the highly enantioselective hydrogenation of 3-substituted pyridines is disclosed. Furthermore, a deep mechanistic study reveals how this high level of stereocontrol can be achieved on substrates where no good results had been reported until now. Part B (Chapter IV to VI) is centered on the problems associated with the high prices of noble metals. Two different solutions have been envisioned in the scientific community to overcome this problem. The first one relies on the replacement of the more commonly used expensive metals for cheap and abundant 1st row transition metals, such as Fe, Co, Ni or Cu. The second approach consists in recycling or reusing the noble metals for more than one reaction. In this regard, tandem catalysis is a commonly applied methodology, where the same metal is used to catalyze at least two different reactions in one pot. In our case, we focused on developing an asymmetric version of the tandem olefin metathesis–hydrogenation. Chapter IV contains an introduction on the topic. In Chapter V and VI, the conversion of different Ru-olefin metathesis catalysts to efficient asymmetric hydrogenation and asymmetric transfer hydrogenation catalysts is described, respectively. These transformations have been subsequently applied to the tandem metathesis-asymmetric hydrogenation and to the metathesis-asymmetric transfer hydrogenation.