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

考虑到全球人口的持续增长、生态问题和自然资源的枯竭，我们面临着为我们的工业过程提供资金的迫切需要。因此，有机化学家有很大的责任提供创新的合成路线，允许从非常简单的、理想的原料、起始材料构建复杂的分子，同时限制步骤数并鼓励催化转化。遵循这些目标，过渡金属催化的C-H活化在过去十年中得到了主要关注。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，同时将总的步数和废物产生降至最低。直接C-H活化也是构建结构复杂的分子和实现铅化合物后期多样化的一个有价值的工具。然而，它的工业应用仍然很少，可能是因为对贵金属催化剂的普遍需求。过渡金属如钯、铑和钚的成本很高，而它们的自然丰度很低，这使得它们不适合工业应用。因此，密集的研究工作最近一直集中在设计基于地球资源丰富、毒性较低和廉价的金属的补充催化系统，包括钴、铁、锰和镍。尤其是钴，已经确立了自己是一种铑的同系物，不仅促进了标准的C-H活化反应，而且在设计新的C-H转化方面被证明是互补的，特别是在其低氧化态。与之形成鲜明对比的是，立体选择性钴催化的C-H活化一直难以实现。因此，AbMetDeFy项目的主要目标是开发一种新的研究计划，即通过低价钴催化的不对称C-H官能化。因此，一系列具有立体结构的外消旋新分子，如轴向手性联芳基、异构体苯乙烯、平面手性二茂铁衍生物和含有C-立体中心的分子，可以在钴催化作用下不对称诱导而被构筑。此外，钴催化剂在很大程度上具有常温下反应条件极其温和的特点，并具有显著的配体加速作用。因此，我们坚信，实现立体选择性的钴催化的C-H活化，尽管具有很高的挑战性，但在学术和工业应用方面都具有极大的吸引力。为了实现这些主要目标，人们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活化；2)不对称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；4)将可见光催化与不对称钴C-H活化相结合，开发无格氏反应的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.