Design, synthesis and catalytic application of water-soluble 1,1′-bis(diphenylphosphino)ferrocene ligands

Abstract

Hydrophilic phosphine ligands have proven indispensable for the translation of metal-catalyzed reactions into aqueous solvent systems and thus for the implementation of safe as well as sustainable chemical processes. Despite numerous reports on water-soluble variants of several renowned ligands, the dppf ligand family has been neglected thus far. Herein, we disclose synthetic strategies towards the first hydrophilic dppf derivatives overcoming issues typically encountered due to their intrinsic oxidizability. Core-sulfonated dppf ligands (meso‑2,2′- or 2,5-disubstituted) were prepared by a directed metalation strategy starting from diisopropyl ferrocene-1,1′-disulfonate. Alternatively, hydrophilic sulfonate or ammonium groups were introduced at the phenyl substituents of dppf. The novel ligands were spectroscopically characterized and showed their catalytic potential in the Pd-catalyzed Tsuji-Trost allylation of amines in water furnishing pharmaceutically relevant N-allylated products (e.g., naftifine, cinnarizine) through a scalable, safe and environmentally benign process.