Reaction mechanisms of catalytic reactions using earth-abundant metals

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Catalytic reactions allow reactions to proceed at lower energies, thus enable the use of more accessible and less reactive starting materials, and to control reaction pathways to improve selectivity and avoid the formation of side products. The implication of catalytic reactions in chemical production and research is thus constantly increasing and an important part of "green", sustainable chemistry. Numerous catalytic reactions used in pharmaceutical research and production are based on platinum-group metals. Despite concerns of metal toxicity, they simply outperform alternatives based on less toxic metals. The research program in this proposal aims at developing efficient alternatives, based on earth-abundant and non-toxic metals, for reactions important in production or research. It is my belief that a general advancement of catalysts can only be achieved from an understanding of the underlying mechanisms. This program focusses on copper-based catalysts and reactions, although other earth-abundant, non-toxic metals might be employed in parallel. This first project of this proposal will focus on improved catalysts for the Chan-Lam (or Chan-Evans-Lam) reaction. The Chan-Lam reaction is the oxidative couplings of nucleophiles with boronic acids, catalyzed by copper salts or complexes, thus replacing similar Pd-catalyzed reactions. Previous work in our group aimed to address the major shortcoming of this reaction, i. e. its unreliability and unpredictability with changing reaction conditions, by using a ligand framework designed to emulate the main intermediate. Forthcoming research will focus on other mechanistic roles of the copper catalyst in the reaction to enhance the steps leading to productive product formation. A second project of this proposal will investigate new catalysts for the catalytic Ullmann-Goldberg reaction. Similar to Chan-Lam reactions, aryl halides are coupled with nucleophiles (typically amines), which offers a wider substrate scope at the cost of lower reactivity. The copper-catalyzed reaction again avoids the use of Pd, but typically requires rather forcing conditions. This new project in our group will follow the approach which proved successful for Chan-Lam couplings, i. e. pre-modelling the most important intermediate by choice of an appropriate ligand design, to improve catalyst performance. A third project will continue our previous work on (stereo-)selective lactide polymerization, aiming at improved production of biodegradable polylactide. Despite large efforts of the research community, highly active and highly isoselective catalysts are still rare. We will approach this problem by exploring a relatively rarely observed stereocontrol mechanism: the ligand-assisted activated monomer mechanism, which introduces stereocontrol into a mechanism more suitable for industrial polymerization conditions. In all cases, catalysts will be based on earth-abundant metals with low toxicity, in particular group IV metals.