REDUCTIONS CATALYZED BY FIRST-ROW TRANSITION METALS

In my thesis Reductions catalyzed by first-row transition metals, I decided to particularly focus on the most abundant transition metal – iron. In the last 15 years, this cheap and non-toxic metal is becoming the object of increasing interest in the scientific community, and a remarkable progress has been made in the development of iron-catalyzed reactions. The new iron catalysts started to reach activities reported so far only for noble metal complexes. Nevertheless, there is still much room for improvement, as many of these iron catalysts are highly air- and/or moisture-sensitive, and their synthesis can be very difficult. In order for the homogeneous iron catalysts to become industrially relevant, more easy-to-prepare and stable catalysts have to be developed. My thesis contributes particularly to the field of asymmetric catalysis, seen often as a domain of noble metals. In my initial work eleven iron complexes with N,N,N,N-ligands were synthesized and tested in catalytic reductions. The negative results obtained with N,N,N,N-ligand complexes in the hydrogenation of C=C and C=O double bonds indicate that N-based tetradentate ligands, despite being an effective option for stabilizing the Fe(II) metal centre, are not particularly good candidates for promoting Fe-catalyzed reductions. In addition to the N-based tetradentate ligand, they require strong π-acceptors like CO, to stabilize the low-valent iron species produced in the course of the reaction. In the following chapter, new iron complexes with isonitrile ligands are described. Overall, three families of iron complexes were synthesized and tested in asymmetric transfer hydrogenation of ketones. The best catalyst was able to induce up to 29% ee in transfer hydrogenation of acetophenone. In order to improve the transfer of the stereochemical information from the (R)-BINOL derived backbone, the introduction of steric bulk in different positions of the molecule was investigated, but no improvement could be obtained. In next chapter, chiral cyclopentadienone(iron) complexes are presented, which represent the core of my PhD work. Compared to other iron complexes used for homogenous asymmetric hydrogenation, (cyclopentadienone)iron complexes have the advantage of being easy to synthesize and stable to air, water and light. By reaction with bases or Me3NO, these complexes can be activated in situ and converted in catalysts for reduction reactions such as the hydrogenation of ketones and imines. A series of eighteen new chiral (cyclopentadienone)iron pre-catalysts were developed. Most of these complexes are derived from (R)-BINOL and differ one from the other in the substitution at the 3,3'-positions of the dinaphthalene backbone, as well as at the 2,5-positions of the cyclopentadienone ring. Among these (R)-BINOL-derived iron complexes, the best one allowed to obtain up to 77% ee in the asymmetric hydrogenation of ketones. Remarkably, this result was nearly three times higher than previously reported in the literature for chiral (cyclopentadienone)iron derivatives. Other approaches to the development of chiral cyclopetadienone(iron) complexes were also investigated, such as replacement of the (R)-BINOL-derived backbone with chiral diamine-derived one, and introduction of stereocentres at the 2,5-positions of the cyclopentadienone ring. However, these approaches did not lead to any improvement, in terms of stereocontrol, with respect to the (R)-BINOL-derived complexes. Building on the expertise achieved with cyclopentadienone(iron) complexes, it was decided to use them in the reduction of substrates different from ketones and imines. In the last experimental chapter, ester hydrogenation with cyclopentadienone(iron) complexes was described. Hydrogenation of a variety of 2,2,2-trifluoroacetate esters could be achieved with a 100% yield, although classical esters remained inactive under these reaction conditions. To conclude, in my work of thesis nearly 40 iron complexes have been developed and tested in catalytic hydrogenation reactions, giving in some cases very promising results, and providing new knowledge and directions for future developments in this field.