Supramolecular regulation of Phosphine ligands for tunable asymmetric Catalysis – SupPhosCat

Control of stereoselectivity in asymmetric catalysis is most frequently achieved by modifying the microenvironment around the metal centre through covalent installation of suitable substituents on the chiral ligand. Unfortunately, it is often necessary to synthesize dozens of catalysts with different steric and electronic properties, thereby leading to a fastidious optimization process. In the framework of SupPhosCat, we will propose a new strategy for the efficient modulation of the second sphere of coordination of a catalytic metal centre, thanks to hydrogen-bonding interactions established between the backbone of a modular ferrocenyl-based phosphine ligand and complementary achiral additives. This strategy will allow us to optimize very efficiently and rapidly a catalytic process because from a set of m chiral ligands and n achiral additives, we can generate m × n catalysts without any synthetic steps. We aim to install an amido-pyridone or isoquinolone group next to the ferrocene unit of the chiral ligand and to use naphthyridin-2-amine derivatives as achiral additives. In addition to molecular additives, supramolecular additives will also be probed for which the naphthyridin-2-amide motif is anchored at the periphery of supramolecular helices based on the benzene-1,3,5-tricarboxamide synthon. The SupPhosCat project is divided into three WPs dealing with the synthesis of two families of SupPhosCat depending whether the additives are molecular or supramolecular (WP1), the implementation of SupPhosCat libraries in asymmetric gold and copper catalysis (WP2), and the characterization of the best-performing complexes (WP3). The possibility to evaluate rapidly large libraries of complexes through iterative deconvolution will be probed with the aim of rapidly identifying one or several catalytic “hits”. Overall, the present project aims to unlock the potential of SupPhosCat in the transformation of challenging substrates or untapped catalytic processes.