Reaction mechanisms of catalytic reactions using earth-abundant metals

利用地球储量丰富的金属进行催化反应的反应机理

• 批准号: RGPIN-2022-03792
• 负责人: Schaper, Frank
• 金额: $ 1.75万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748708
• 关键词: Reaction; mechanisms; catalytic; reactions; using

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.

催化反应允许反应在较低的能量下进行，从而能够使用更容易获得且反应性较低的起始材料，并控制反应途径以提高选择性并避免副产物的形成。因此，催化反应在化学生产和研究中的意义不断增加，并且是“绿色”，可持续化学的重要组成部分。在药物研究和生产中使用的许多催化反应都是基于铂族金属。尽管存在金属毒性的问题，但它们的性能完全优于基于毒性较低的金属的替代品。该提案中的研究计划旨在开发基于地球上丰富且无毒的金属的高效替代品，用于生产或研究中重要的反应。我相信，催化剂的普遍进步只能从对潜在机制的理解中实现。该计划侧重于铜基催化剂和反应，尽管其他地球丰富的无毒金属可能会平行使用。 该提案的第一个项目将集中于改进Chan-Lam（或Chan-Evans-Lam）反应的催化剂。Chan-Lam反应是亲核试剂与硼酸的氧化偶联反应，由铜盐或络合物催化，从而取代类似的Pd催化反应。我们小组以前的工作旨在解决这种反应的主要缺点，即。e.其不可靠性和不可预测性与变化的反应条件，通过使用配体框架设计，以模拟主要中间体。未来的研究将集中在铜催化剂在反应中的其他机械作用，以提高生产性产品形成的步骤。 该提案的第二个项目将研究催化Ullmann-Goldberg反应的新催化剂。类似于Chan-Lam反应，芳基卤化物与亲核试剂（通常为胺）偶联，这以较低的反应性为代价提供了更宽的底物范围。铜催化的反应再次避免使用Pd，但通常需要相当强制的条件。我们小组的这个新项目将遵循Chan-Lam耦合器成功的方法，即。e.通过选择合适的配体设计来预模拟最重要的中间体，以改善催化剂性能。第三个项目将继续我们以前的工作（立体）选择性丙交酯聚合，旨在提高生物降解聚乳酸的生产。尽管研究界付出了巨大的努力，但高活性和高等选择性的催化剂仍然很少见。我们将探讨这个问题，通过探索一个相对很少观察到的立体控制机制：配体辅助活化单体机制，它引入立体控制到一个更适合于工业聚合条件的机制。在所有情况下，催化剂将基于具有低毒性的地球上丰富的金属，特别是第IV族金属。