A New Generation of Iron-based Hydrogenation Catalysts

The catalytic reduction of polar multiple bonds such as carbonyl functionalities via molecular hydrogen plays a significant role in modern synthetic organic chemistry. Especially the stereoselective hydrogenation of ketones to yield enantiomerically pure alcohols is a key technology for the synthesis of fine chemicals, perfumes, and pharmaceuticals. This reaction is excellently performed by many transition metal complexes containing noble metals such as ruthenium, rhodium, or iridium. Many of these hydrogenation reactions involve ligand-metal bifunctional catalysis (metal-ligand cooperation). However, the limited availability of precious metals, their high price, and their toxicity diminish their attractiveness in the long run and more economical and environmentally friendly alternatives have to be found. In this respect, the preparation of well-defined iron-based catalysts of comparable activity would be desirable and is thus a major challenge for the development of more sustainable reduction reactions. Iron is the most abundant transition metal in the earth crust, and ubiquitously available. Moreover, it has to be noted that nature often uses iron-based catalysts such as hydrogenases for hydrogenations which also seem to proceed via bifunctional catalysis. The underlying project is dealing with the modular design of new, inexpensive, and easy-to-handle chiral and achiral iron(II) complexes possessing both acidic and basic sites - bifunctional catalysts - for the subsequent preparation of optically pure alcohols. The first step will involve the synthesis of a versatile set of ligands featuring P-N bonds including derivatives of 2-aminiopyridine and 2,6-diaminopyridine. The synthesis is easily achieved via coupling of primary and secondary amines with R2 PCl. The latter are either commercially available or are easily prepared from PCl 3 and the corresponding achiral and chiral diols, diamines, or aminoalcohols. Accordingly, all ligands are accessible in modular fashion based on simple synthetic methodologies. A useful feature of these ligands is that steric, electronic, and particularly stereochemical parameters can be manipulated by modifications of the phosphino and amino moieties in order to control the reactivity at the metal center. Thorough investigation of the complexation of the new ligands with various sources of iron will reveal main patterns in their co-ordination behavior. Determination of the structurual and spectral characteristics of the obtained metal complexes will establish correlations between these and the ligand`s nature. Of particular relevance is the control of the spin state by the choice of ligands. The novel complexes will be applied for the asymmetric hydrogenation of ketones. In addition, investigation of the reaction mechanisms by spectral methods and/or isolation of intermediates the key factors which are responsible for chemical and optical yields will be evaluated.

In sum, this project generated a fundamental understanding of new concepts in the area of Sustainability through Base Metal Catalysis. This led to the development of efficient iron-based catalysis in reactions formerly restricted to noble metals, and resulted in the development of new, environmentally benign catalytic processes. Driven by both public demand and government regulations, pharmaceutical and fine chemical manufacturers are increasingly seeking to replace stoichiometric reagents as well as precious metal based catalysts. This modifications used in synthetic transformations will develop greener, safer, and more cost-effective chemical processes. A process we were interested in was and still is the catalytic hydrogenation of multiple bonds via molecular hydrogen. This plays a significant role in modern synthetic organic chemistry for the production of flavors, fragrances and pharmaceuticals and is excellently performed by many transition metal complexes containing noble metals such as ruthenium, rhodium, or iridium. The limited availability of precious metals, their high cost, and their toxicity diminish their attractiveness in the long run. Thus, more economical and environmentally friendly alternatives have to be found which are in line with green chemistry guidelines. In this context, it is important to mention that iron is the most abundant transition metal in the earth crust, ubiquitously available, and non-toxic.This project aimed at the discovery, development, and implementation of new catalytic methodologies based on iron catalysts which open the door to the sustainable production of pharmaceuticals and fine chemicals (Sustainability through Base Metal Catalysis). In the course of this project, we were able to develop well-defined iron-based catalysts for the hydrogenation of aldehydes and ketones to alcohols, which displayed comparable or even higher activity than precious metals. Moreover, these catalysts were also very active for the hydrogenation of CO2, a greenhouse gas, to yield formic acid. In addition, we also started to develop related chemistry with other base metals such as cobalt, nickel, vanadium, and molybdenum. The outcome of this project is documented in 11 scientific publications in highly ranked peer-reviewed journals.