A modular way towards biaryls: Highly enantioenriched biphenyls can be prepared based on a transition-metal-free aryl-aryl coupling followed by efficient desymmetrization or deracemization and chemoselective functionalization (see scheme).

Upon treatment of various aryllithium intermediates with 1,2-dibromobenzene or 1-bromo-2-iodobenzene, dissymmetrical ortho,ortho'-di-, triand even tetrasubstituted bromo-or iodobiaryls become readily available. The crucial steps in all these reactions were the nucleophilic addition of the organolithium precursor to a transient aryne species released from it by b-elimination of a lithium halide and, stabilization of the resulting 2-biaryllithium intermediate by in situ transfer of bromine or iodine from the starting material. This straightforward transition metal-free access to biaryls allows the preparation of highly valuable halobiaryls on a gram scale in excellent yields. These precursors can be subsequently functionalized by highly regioselective halogen/metal permutations into a vast variety of target molecules. This was demonstrated in the synthesis of several mono-and diphosphine ligands.

A new family of C(1)-symmetric bis(diphenylphosphino)biphenyls have been prepared starting from readily available ortho,ortho'-dihalobiphenyl precursors by a palladium-catalyzed C-P coupling reaction. This process does not require the use of an additional ligand. To date, the synthesis of such diphosphines, by reaction of an intermediate biphenyldiyl dianion with ClPPh(2), mainly afforded the undesired cyclic phosphafluorene derivative. So far, no synthetic pathway has been found to avoid this intramolecular reaction. Herein we report the first general and external-ligand-free palladium-catalyzed phosphination reaction that allows the synthesis of a wide variety of substituted ortho,ortho'-bis(diphenylphosphino)biphenyls. With the aim of illustrating the scope and efficiency of this methodology, we applied it to the establishment of a straightforward access to C(1)-symmetrical analogues of the most powerful ligands used in homogenous catalysis and extended it to more challenging substrates.