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

考虑到世界人口的不断增长，生态问题和自然资源的枯竭，我们正面临着迫切需要为我们的工业过程提供资金。因此，有机化学家有责任提供创新的合成路线，允许从非常简单的，理想的原料，起始材料构建复杂分子，同时限制步骤数量并鼓励催化转化。在这些目标之后，过渡金属催化的碳氢化合物活化在过去十年中获得了主要的关注。事实上，它允许选择性功能化未活化的C-H键作为潜在的官能团，将简单的前体转化为复杂的分子支架，同时最大限度地减少总体步骤数和废物产生。直接C-H活化也是构建结构复杂分子和允许先导化合物后期多样化的有价值的工具。然而，它的工业应用仍然很少，可能是由于普遍需要贵金属催化剂。钯、铑和钌等过渡金属的高成本和低天然丰度使得它们不适合工业应用。因此，密集的研究工作最近集中在设计基于地球上丰富的，毒性较小的和廉价的金属的互补催化系统，包括钴，铁，锰和镍。特别是钴，已经确立了自己作为铑的同系物，不仅促进催化标准的碳氢活化反应，而且在设计新的碳氢转化方面被证明是互补的，特别是在它的低氧化状态下。与之形成鲜明对比的是，立体选择性钴催化的碳氢化合物活化一直是难以捉摸的。因此，AbMetDeFy项目的主要目标是开发一个新的研究项目，即通过低价钴催化的不对称碳氢化合物功能化。因此，在没有不对称诱导的情况下，钴催化可以构建一系列立体的、外消旋的新分子，如轴手性双芳基、atropoisom异构苯乙烯、平面手性二茂铁衍生物和含有c -立体中心的分子。此外，钴催化剂在环境温度下的反应条件非常温和，并且具有明显的配体加速度。因此，我们坚信，实现立体选择性钴催化的C-H活化，尽管极具挑战性，但对学术和工业应用都极具吸引力。为了实现这些主要目标，提出了四种不同的策略：1)手性导向基团非对映选择性活化C-H；2)对映选择性C-H功能化；3)设计前所未有的定义良好的手性钴(I)催化剂；4)通过可见光催化与不对称钴C-H活化的合并，开发无格氏碳氢转化。

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.