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

考虑到全球人口的不断增长、生态问题和自然资源的枯竭，我们面临着对工业流程进行退款的迫切需要。因此，有机化学家肩负着提供创新合成路线的重大责任，该路线允许从非常简单、理想的原料、起始材料构建复杂的分子，同时限制步骤数量并鼓励催化转化。遵循这些目标，过渡金属催化的 C-H 活化在过去十年中受到了广泛关注。事实上，它允许将未激活的 C-H 键选择性官能化为潜在官能团，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实现先导化合物后期多样化的重要工具。然而，其工业应用仍然稀缺，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及其低自然丰度使得它们不适合工业应用。因此，最近的深入研究工作集中在设计基于地球丰富、毒性较小且廉价的金属（包括钴、铁、锰和镍）的补充催化系统。特别是钴，已被确立为铑同系物，不仅能催化标准的 C-H 活化反应，而且在设计新型 C-H 转化中被证明是互补的，特别是在其低氧化态时。与此形成鲜明对比的是，立体选择性钴催化的C-H活化一直难以捉摸。因此，AbMetDeFy项目的主要目标是开发一个新的研究计划，即通过低价钴催化的不对称C-H官能化。因此，一系列立体异构但外消旋的新型分子，例如轴向手性联芳基、阻转异构苯乙烯、平面手性二茂铁衍生物和含有C-立构中心的分子可以通过钴催化构建，但没有不对称诱导。此外，钴催化的主要特点是在环境温度下反应条件极其温和，并且具有显着的配体加速作用。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，但对于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）手性导向基团的非对映选择性 C-H 激活； 2) 对映选择性C-H官能化； 3）设计前所未有的明确的手性钴（I）催化剂，4）通过将可见光光催化与不对称钴C-H活化相结合来开发无格氏C-H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.