Design and development of molecularly-defined catalysts for efficient synthesis of amino alcohol and amino acid precursors

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The main goal in SP1 is the development of key synthetic methodologies and catalysts. Starting from olefins in a catalytic cascade reaction valuable α-hydroxy ketones will be directly prepared. The basis of this novel transformation is a domino hydroformylation-Umpolung reaction (or better domino hydroformylation-cross acyloin-cascade), which will be performed using metal complexes (catalyst for the carbonylation step) and carbenes (catalyst for the Umpolung step). Following this concept, new and existing ligands and the resulting catalysts will be tested. Initially, a combination of the two catalytic systems will be applied and tested at the same time. Then, integrated bi-functional catalysts will be prepared by introducing catalytic properties in the phosphine ligands utilizing carbene-substituted phosphines. To rationally design a suitable catalyst system, a close cooperation with SP6 will be done, where a set of descriptors for the experimentally applied catalysts (Rh, Co) and phosphorus ligands is used to predict better performance. The innovative catalytic approach for the direct synthesis of α-hydroxy ketones and α-keto acid derivatives from easily available olefins provides the basis for the preparation of enantiopure β-aminoalcohols and α-amino acids utilizing modern oxidations (SP2) and biocatalysis (SP3). Exemplarily, this development will be performed utilizing two benchmark olefins (styrene and 1-octene) which are representative for a broad diversity of olefins. To achieve this goal, the yield of the selected benchmark products, which will be used also by all other PI´s for their respective investigations, should be optimized in WP 1 and WP 2. Here, specifically variations of the catalyst system – both metals and ligands – will be the central focus. Apart from screening approaches to identify the optimal catalyst system, we would like to obtain deeper insights into the mechanism to support a more rational catalyst development. In cooperation with SP5 mechanistic and kinetic studies for an in-depth understanding and modeling of the cascade process steps will be done. In this respect, it should be also mentioned that in our optimization studies, we aim to get high quality data, rather than simply doing high-throughput experimentation. After the selection of suitable catalytic systems, which will be the basis for all subsequent developments, critical reaction parameters such as temperature, partial pressures, solvent systems, etc. will be optimized also utilizing DOE. Next, designed bifunctional catalysts with all necessary active sites integrated in a molecularly defined structure will be synthesized (WP 3). Naturally, the basis for this catalyst design will start from results obtained in WP 1 and WP 2 and in cooperation with SP6 to select improved ligands.