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

• Applicant: Professor Dr. Lutz Ackermann
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2017 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 391136690

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.

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partner: Dr. Joanna Wencel-Delord