Computational Modeling of Complex Chemical Transformations in Homogeneous Catalysis

Abstract

Catalysis is involved in most manufactured products and hence it is highly important for supplying the society with energy, food, pharmaceuticals and other goods. In recent years, increasing attention has been paid to the development of “green” catalytic processes for the production of valuable chemical entities that are competitive with current industrial synthetic routes while reducing at the same time the use of hazardous chemicals and waste generation. Importantly, the catalyst has to be as selective as possible in order to facilitate only those reaction pathways that lead to the desired product. Quantum-chemical calculations provide fundamental insights into the mechanism of catalytic transformations and into the role of the catalyst. Some of the key challenges of contemporary <em>in silico</em> catalytic research are: modeling of large and flexible catalysts or substrates, deciphering the influence of noncovalent interactions on the selectivity of enantioselective transformations, elucidating environmental or cooperative catalytic effects, and describing accurately reaction intermediates with complicated electronic structures. In this thesis, computational multi-level protocols (including semi-empirical, density functional theory and wave-function based methods) are developed to address these key challenges in the field of selective homogeneous catalysis. The importance of noncovalent interactions for the stereoselectivity, the shape of the catalytic pocket and the reaction rates is discussed for the intramolecular hydroalkoxylation of small and unactivated olefins catalyzed by modern organocatalysts. To elucidate cooperative catalytic effects in enantioselective organocatalysis, the general dimerization mechanism for Brønsted acid catalysts of various sizes and structural features as well as the influence of catalyst dimerization effects on the formation of aliphatic β³-amino acid derivates from silyl nitronates as a case study is investigated and rules of thumb are provided for determining under which conditions several catalyst molecules can participate in the rate- and/or selectivity-determining reaction steps. The accurate description of solute-solvent interactions is crucial for the modeling of homogeneously catalyzed reactions. This aspect is studied for the conformational preference of molecular balances in solution. Effects of the electronic structure on the mechanism and catalytic efficiency are unveiled considering the aminofunctionalization of styrene catalyzed by small and simple iron(II) catalysts as a case study.