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

The beginning of this century is clearly marked by profound social changes. Indeed, while considering, on one hand, the continuously growing worldwide population and, on the other hand, ecological issues and depletion of natural resources, we are facing an urgent need for refunding our industrial process. Offering alternative solutions to ensure needs of our society in more sustainable and eco-compatible manner is, thus, of prime importance. Accordingly, the scientists and in particular organic chemists have a strong responsibility to design and provide innovative synthetic routes allowing the construction of complex and high value added 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 from the scientific community. Indeed, direct C-H activation 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. In addition, direct C-H activation has established itself as a valuable tool to construct biologically active, structurally complex molecules. It is noteworthy that late-stage diversification of lead compounds is highly attractive. However, despite of the remarkable potential of C-H activations in academia, its industrial applications continue to be scarce. A considerable limitation of the C-H activation field towards large-scale applications is represented by 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. To overcome this limitation, the scientific community has been focusing in recent years intensive research efforts 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 progressively established itself as a rhodium congener, being particularly effective in different oxidation states. Interestingly, cobalt catalyses not only enlabed “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, with only two examples for simple addition reactions.

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 within a dual catalysis regime.