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

次级方案1的主要目标是开发关键的合成方法和催化剂。以烯烃为原料，通过催化级联反应直接制备有价值的α-羟基酮。这种新的转化的基础是多米诺氢甲酰化-Umpolung反应（或更好的多米诺氢甲酰化-交叉偶姻-级联），其将使用金属络合物（用于羰基化步骤的催化剂）和卡宾（用于Umpolung步骤的催化剂）进行。根据这一概念，将测试新的和现有的配体和所得的催化剂。最初，将同时应用和测试两种催化系统的组合。然后，将通过利用卡宾取代的膦在膦配体中引入催化性能来制备集成的双功能催化剂。为了合理设计合适的催化剂体系，将与SP 6密切合作，其中使用一组实验应用的催化剂（Rh，Co）和磷配体的描述符来预测更好的性能。从易得的烯烃直接合成α-羟基酮和α-酮酸衍生物的创新催化方法为利用现代氧化（SP2）和生物催化（SP3）制备对映体纯的β-氨基醇和α-氨基酸提供了基础。例如，将使用两种基准烯烃（苯乙烯和1-辛烯）进行该开发，这两种基准烯烃代表了广泛的烯烃多样性。为了实现这一目标，在WP 1和WP 2中，应优化所选基准产品的产量，所有其他PI也将使用这些产品进行各自的研究。在这里，特别是催化剂体系的变化-金属和配体-将是中心焦点。除了筛选方法以确定最佳催化剂体系外，我们还希望更深入地了解机理，以支持更合理的催化剂开发。与次级方案5合作，将进行深入了解级联工艺步骤和建模的机理和动力学研究。在这方面，还应该提到的是，在我们的优化研究中，我们的目标是获得高质量的数据，而不是简单地进行高通量实验。在选择合适的催化体系（这将是所有后续开发的基础）之后，还将利用DOE优化关键反应参数，如温度、分压、溶剂体系等。接下来，设计的双功能催化剂与所有必要的活性位点集成在一个分子定义的结构将被合成（WP 3）。当然，这种催化剂设计的基础将从WP 1和WP 2中获得的结果开始，并与SP 6合作选择改进的配体。

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.