Reaction mechanisms of catalytic reactions using earth-abundant metals

催化反应允许反应以较低的能量进行，因此可以使用更容易获得和反应性较低的起始材料，并控制反应途径以提高选择性和避免形成副产物。因此，催化反应在化学生产和研究中的意义不断增加，是“绿色”、可持续化学的重要组成部分。许多用于药物研究和生产的催化反应都是基于铂族金属。尽管担心金属毒性，但它们的性能优于基于毒性较小的金属的替代品。本提案中的研究计划旨在开发高效的替代品，以地球上丰富的无毒金属为基础，用于生产或研究中重要的反应。这是我的信念，一个普遍的进步的催化剂，只能从了解其潜在的机制。该计划侧重于铜基催化剂和反应，尽管其他地球上丰富的无毒金属也可以并行使用。本提案的第一个项目将侧重于改进Chan-Lam（或Chan-Evans-Lam）反应的催化剂。Chan-Lam反应是由铜盐或配合物催化的亲核试剂与硼酸的氧化偶联，从而取代类似的pd催化反应。我们小组先前的工作旨在通过使用设计用于模拟主要中间体的配体框架来解决该反应的主要缺点，即随着反应条件的变化其不可靠性和不可预测性。未来的研究将集中在铜催化剂在反应中的其他机制作用，以提高导致生产产物形成的步骤。该提案的第二个项目将研究催化Ullmann-Goldberg反应的新催化剂。与Chan-Lam反应类似，芳基卤化物与亲核试剂（通常是胺）偶联，以较低的反应活性为代价，提供了更广泛的底物范围。铜催化的反应同样避免了钯的使用，但通常需要相当强的条件。我们小组的这个新项目将遵循Chan-Lam偶联的成功方法，即通过选择合适的配体设计对最重要的中间体进行预建模，以提高催化剂的性能。第三个项目将继续我们之前在（立体）选择性丙交酯聚合方面的工作，旨在改进生物可降解聚丙交酯的生产。尽管研究界做出了巨大的努力，但高活性和高等选择性催化剂仍然很少。我们将通过探索一个相对较少观察到的立体控制机制来解决这个问题：配体辅助活化单体机制，它将立体控制引入了一个更适合工业聚合条件的机制。在所有情况下，催化剂将基于地球上丰富的低毒性金属，特别是IV族金属。

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.