C$_{1}$-symmetrische Phosphoramidit-Liganden für Nickel-katalysierte C-C-Kupplungsreaktionen

Langensiepen, Fabian Marius; Leitner, Walter (Thesis advisor); Klankermayer, Jürgen (Thesis advisor)

Düren : Shaker (2022)
Book, Dissertation / PhD Thesis

In: Berichte aus der Chemie
Page(s)/Article-Nr.: 262 Seiten : Illustrationen, Diagramme

Dissertation, RWTH Aachen University, 2021


This thesis deals with the synthesis of chiral phosphorus ligands for homogeneous asymmetric transition metal catalysis. This catalysis is one of the most important sources for the production of chiral compounds. To achieve the necessary enantiomeric purity, ligands are needed to control these reactions. Effective ligands are not yet available for all reactions. Based on this problem, this thesis deals with the synthesis of new ligands, which belong to the class of phosphoramidites. The ligand class of the phosphoramidites could already give excellent results in some catalyses. In the present work the newly synthesized ligands are used in two nickel-catalyzed C-C coupling reactions. The introduction to this thesis shows the development of homogeneous catalyst systems and their application in catalysis. The ligand class of phosphoramidites, their modular synthesis and their application in asymmetric catalysis, especially in hydrovinylation and cycloisomerization, will be particularly highlighted. In this class of ligands the potential as well as the activity change by changing the structure are shown and from this the problem of the work is derived.In chapter 3 the results of the work are presented and discussed. This chapter is divided into three under chapter. The ligand synthesis, the hydrovinylation and the cycloisomerization. The chapter 3.1 explains the synthesis strategies of the phosphoramidite ligands. For this purpose, numerous new chiral imines and secondary amines were synthesized, which were then used as "building blocks" for the synthesis of the ligands. For the synthesis, a literature known modular synthesis route is used and then adapted to the "building blocks" that are used. The synthesis route is used to display the required ligands in the further course of the work. The thirty-four newly synthesized phosphoramidite ligands differ in different structural features. By variation of individual building blocks of the ligand (amine, carbonyl or BINOL unit) and associated changes in the electrical and steric properties, the performance in homogeneous asymmetric transition metal catalysis is influenced. The newly synthesized ligands have been compiled in a ligand library.In chapter 3.2 of the work considers the use of the new ligands in Ni-catalyzed hydrovinylation. First of all, the catalysis process is optimized by hydrovinylation of styrene with the Feringa-ligand to such an extent that reproducible results can be achived and several catalyses can be run in parallel. Subsequently, newly synthesized phosphoramidite ligands are tested in catalysis and, depending on the results, the individual building blocks of the ligand are modified. An iterative optimization of the ligand for this specific application is performed. With this method, it was possible to achive enantiomeric surpluses of 98 % in the hydrovinylation of styrene. The performance of the newly developed ligands is tested by using cyclohexa-1,3-diene as a second substrate. By optimizing the ligands, a 92 % enantiomeric excess of this substrate could be obtained during hydrovinylation. Finally, in this part of the work the catalysis cycle of hydrovinylation of styrene is considered. For selected ligands, the catalytic cycles are calculated with DFT methods and the results (ee and activity) are compared with the experimental values. The very good agreement of the obtained data verifies the applied computational chemical approach, which is now available for a predictive further development of the ligand structure. In chapter 3.3 of the thesis a related reaction of hydrovinylation is considered, the Ni-catalyzed cycloisomerization. As in hydrovinylation, two substrates - diethyldiallyl malonate and N,N-diallyl-4-methylbenzenesulfonamide - are investigated in this catalysis. In the cycloisomerization of the benchmark substrate diethyldiallylmalonate, enantiomeric surpluses of up to 80 % could be achived by gradually modifying and optimizing the phosphoramidite ligands. For the second substrate N,N-diallyl-4-methylbenzenesulfonamide, the enantiomeric excess obtained was up to 73 %.