Noble applications of abundant metals: Asymmetric Co, Ni, Fe and Mn-catalyzed C-H activation

丰富金属的高贵应用：不对称 Co、Ni、Fe 和 Mn 催化的 C-H 活化

• 批准号: 391136690
• 负责人: Professor Dr. Lutz Ackermann
• 金额: --
• 依托单位: Institut für Organische und Biomolekulare Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/391136690?language=en
• 关键词: Noble; applications; abundant; metals; Asymmetric

Considering the continuously growing worldwide population, ecological issues and depletion of natural resources, we are facing an urgent need for refunding our industrial process. Accordingly, the organic chemists have a strong responsibility to provide innovative synthetic routes allowing the construction of complex molecules from very simple, ideally feedstock, starting materials while limiting number of steps and encouraging catalytic transformations. Following these objectives, transition metal-catalysed C-H activation has gained, over the last decade, a major attention. Indeed, it allows for the selective functionalisation of unactivated C-H bonds as latent functional groups, transforming simple precursors into complex molecular scaffolds while minimizing the overall step count and waste generation. Direct C-H activation is also a valuable tool to construct structurally complex molecules and to allow late-stage diversification of lead compounds. However, its industrial applications continue to be scarce, probably due to the general need for precious metal catalysts. The high costs of the transition metals like palladium, rhodium and ruthenium and their low natural abundance render those non-ideal for industrial applications. Accordingly, intensive research efforts have been focusing recently on designing complementary catalytic systems based on earth-abundant, less toxic and cheap metals, including cobalt, iron, manganese and nickel. In particular cobalt, has been establishing itself as a rhodium congener, prompt to catalyse not only standard C-H activation reactions, but proved complementary in devising novel C-H transformations, in particular at its low oxidation state. In sharp contrast, stereoselective cobalt-catalysed C-H activation has been elusive.Accordingly, the main goal of the AbMetDeFy project is to develop a new research program, namely asymmetric C-H functionalisation by means of low-valent cobalt-catalysis. Thus, an array of stereogenic, yet racemic novel molecules, such as axially-chiral biaryls, atropoisomeric styrenes, planar-chiral ferrocene derivatives and molecules containing C-stereocentres can be constructed by cobalt catalysis, however, with no asymmetric induction. In addition, cobalt catalyses are largely characterized by exceedingly mild reaction conditions at ambient temperature, and feature significant ligand acceleration. Hence, we are strongly convinced that achieving stereo-selective cobalt-catalyzed C-H activation, albeit being highly challenging, is extremely attractive for both academic as well as industrial applications. To achieve these major goals four different strategies are proposed: 1) diastereoselective C-H activation with chiral directing groups; 2) enantioselective C-H functionalisations; 3) design of unprecedented well-defined chiral cobalt(I) catalysts and 4) development of Grignard-free C-H transformations by merging of visible-light photocatalysis with asymmetric cobalt C-H activation.

考虑到全球人口不断增长，生态问题和自然资源的耗尽，我们正面临退还我们的工业过程的迫切需求。因此，有机化学家有强大的责任提供创新的合成途径，从而允许从非常简单，理想的原料，起始材料中构建复杂分子，同时限制步骤数量并鼓励催化转化。遵循这些目标，在过去的十年中，过渡金属催化的C-H激活获得了主要关注。确实，它允许将未激活的C-H键选择性官能化为潜在的功能组，从而将简单的前体转化为复杂的分子支架，同时最大程度地减少整体步骤计数和废物的产生。直接C-H激活也是构建结构复杂分子并允许铅化合物的晚期多样化的有价值的工具。但是，它的工业应用仍然很少，这可能是由于普遍需要贵金属催化剂。过渡金属的高成本，例如钯，菱形和琼脂及其自然丰度低，使那些非理想的工业应用。因此，密集的研究工作最近一直集中在设计基于土壤丰富，毒性较小和廉价金属的互补催化系统上，包括钴，铁，锰和镍。尤其是钴，一直以菱形同步物的形式建立自己，不仅促进了标准的C-H激活反应，而且在设计新型的C-H转化方面被证明是互补的，尤其是在其低氧化状态下。相比之下，立体选择性的钴催化的C-H激活是难以捉摸的。依据，Abmetdefy项目的主要目标是通过低价值钴催化剂来制定新的研究计划，即不对称的C-H功能化。因此，一系列的立体生成剂但外星人的新分子，例如轴向性屈肌，抗骨异构体的苯甲酸酯，平面 - 二苯基二陈代衍生物和含有c-替代中心的分子，可以由钴催化构建，但没有辅助诱导。此外，钴催化剂的特征在很大程度上是在环境温度下极度轻度的反应条件，并具有明显的配体加速度。因此，我们坚信，尽管如此，即使在学术和工业应用方面都极具挑战性，即可实现立体选择性钴催化的C-H激活，尽管具有极大的挑战。为了实现这些主要目标，提出了四种不同的策略：1）用手性指导组激活非映选择C-H激活； 2）对映选择性C-H功能化； 3）设计了前所未有的明确的手性钴（I）催化剂和4）通过将可见光光催化与不对称钴C-H激活合并，从而开发了无尖齿的C-H转化。