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，我们正面临着为我们的工业进程重新提供资金的迫切需要。因此，有机化学家肩负着提供创新合成路线的重大责任，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C-H活化在过去十年中获得了主要关注。事实上，它允许未活化的C-H键作为潜在官能团的选择性官能化，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，其工业应用仍然很少，可能是由于对贵金属催化剂的普遍需求。过渡金属如钯、铑和钌的高成本和它们的低天然丰度使得它们对于工业应用不是理想的。因此，最近的密集研究工作一直集中在设计基于地球上丰富的、毒性较小和廉价的金属，包括钴、铁、锰和镍的互补催化系统。特别是钴，已经确立了它本身作为铑同系物的地位，不仅迅速催化标准的C-H活化反应，而且证明在设计新的C-H转化中是互补的，特别是在其低氧化态下。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计划，即通过低价钴催化的不对称C-H官能化。因此，一系列的立体，但外消旋的新分子，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分子含有C-立构中心，可以通过钴催化构建，然而，没有不对称诱导。此外，钴催化剂的主要特征在于在环境温度下极其温和的反应条件，并且具有显著的配体加速作用。因此，我们坚信，实现立体选择性钴催化的C-H活化，尽管具有很大的挑战性，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）用手性导向基团进行非对映选择性C-H活化; 2）对映选择性C-H官能化; 3）设计前所未有的定义明确的手性钴（I）催化剂;以及4）通过合并可见光催化剂与不对称钴C-H活化来开发无格氏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.