C-H Functionalisation via Migratory Cross-Couplings and Enantioselective Pd0-Catalysed C(sp2)-H Arylation

The ubiquitous nature of C-H bonds renders their direct and selective functionalisation very appealing and research in that field became one of the most important topics in organic chemistry. As a consequence, elegant methods to functionalise all sorts of C-H bonds have emerged. They opened new disconnection paradigms and more step- and atom-economical approaches. The current manuscript addresses two distinct strategies pursued by our group in this context: the remote functionalisation of C(sp3)-H bonds via migratory cross-couplings and the generation of molecular complexity through ring-forming Pd0-catalysed C-H activation reactions.
Driven by our interest in the development of transition metal-catalysed process for the valorisation of cheap and abundant hydrocarbons feedstocks, we first sought to develop a general nickel-catalysed migratory Kumada cross-coupling for the linear-selective functionalisation of alkyl chains. We also studied the opportunity to optimise an equivalent iron-promoted transformation. Despite intense efforts, both of our protocols suffered from a lack of generality and failed to compete with the best established methods. In parallel, we also aimed to develop nickel- and palladium-catalysed approaches for the remote arylation of methylene groups of terminal alkyl bromides and olefins, without more success.
In a second time, we developed an enantioselective Pd0-catalysed C(sp2)-H arylation protocol for the preparation of fluoradenes and other aromatic-rich warped molecules, as a new tool for the bottom up synthesis of chiral polycyclic aromatic hydrocarbons (PAHs). In spite of their importance in the field of organic electronic materials, these fullerene fragments are still often prepared as racemates and enantiomerically pure samples obtained by chromatographic separation. The approach that we propose to fill this synthetic gap relies on the unique role played by chiral bifunctional phosphine-carboxylate ligands during the enantiodetermining concerted metalation-deprotonation (CMD) step. We prepared a diverse array of compounds in high yields and with good to excellent enantioselectivity via the formation of ring systems of different sizes. Finally, we studied the photophysical and chiroptical properties of some of these products.