Ferrocene based ligands have been highly successful, and indeed are one of the so-called “privileged” ligand structures due to the excellent selectivities typically reported in asymmetric hydrogenation reactions, among others. Examples in commercial use include JosiPhos, TaniaPhos and WalPhos, used in the synthesis of Active Pharmaceutical Ingredients (APIs) and Agrochemicals.
This project involved developing a new synthetic route to high-value catalysts, allowing easier access to these molecular structures. Initially this focused on a route to enantiopure P-chiral ferrocenyl phosphines. A five-step synthesis was employed, using ephedrine as a chiral auxiliary. The route was modular, and allowed the introduction of various substituents on the phosphorus atom. Three separate syntheses with varying substituents were evaluated, and the optimal group (ortho-tolyl) was identified. The synthesis proved successful, and the desired ferrocenyl compound was formed in good yields. The resulting product contains not only a chiral phosphorus centre, but also an oxide functionality, allowing further reactivity to be precisely controlled through directed ortho-metallation techniques. Studies to evaluate the ortho-functionalisation of this compound and its applications in catalysis are currently ongoing.