The development of new methodologies for the preparation of biologically and industrially interesting compounds remains one of the fundamental challenges in chemistry. Aryl-aryl bond formation is one of the most important tools in modern organic synthesis. These biaryl motifs are very often found in pharmaceutical, agrochemicals, organic materials and natural products. Given the abundance of C–H bonds in organic molecules, the selective activation and use of these bonds in controlled synthetically useful transformations is an immensely important topic. In this context, direct C–H arylation has emerged as a powerful methodology for the synthesis of biaryls. However, in most methodologies described so far, the arene substrate must fulfil certain requirements such as containing strong electron-withdrawing or electron-donating groups, or bearing special directing groups. Substrates lacking this feature either are unreactive or must be used in large excess. The coupling of ‘simple arenes’, which are not considered as π-electron-deficient or -rich remains challenging.
On this basis we envisioned a methodology in which the π-coordination of non-activated arenes to a metal fragment promotes the C-H arylation reaction catalysed by palladium. We designed a new approach based on a system fully catalytic in both transition metals, Pd used for mediating the cross-coupling and Ru used for enhancing the reactivity of the arene via π-complexation.
To develop this new catalytic methodology three milestones have to be met. First, a suitable method for stoichiometric C-H arylation of π-coordinated arenes has to be found. Then, conditions for effective arene exchange between the bisarylated complex and simple arenes have to be developed. Finally, these two steps have to be merged together to develop a methodology that is catalytic in both Pd and the π-arene metal complex.
Unfortunately, it was impossible to achieve enough catalytic activity for this process. Nevertheless, we applied the knowledge acquired during the process along with the group experience to develop a direct arylation‐cyclisation reaction for the construction of medium‐sized rings promoted by π-complexation of fluoroarenes to chromium tricarbonyl fragment and a catalytic asymmetric C-H arylation of (π-arene)-chromium complexes which allows facile access to planar-chiral phosphines.
