Tunable Unsymmetrical Ferrocene Ligands Bearing a Bulky Di-1-adamantylphosphino Motif for Many Kinds of Csp2–Csp3 Couplings

A class of ferrocene-based unsymmetrical bidentate ligands containing a di­(1-adamantyl)­phosphino group, Fc­(PAd2)­(PR2) (R = Ph, Cy, iPr, tBu) abbreviated as MPhos ligands, and their corresponding (MPhos)­PdCl2 pre-catalysts were synthesized in very good yields and fully characterized using techniques including single-crystal X-ray crystallography. These pre-catalysts were utilized for Csp2–Csp3 couplings for many kinds of name reactions such as Murahashi–Feringa, Kumada–Corriu, Negishi, and Suzuki–Miyaura with good substrate scope and isolated yields. About nine “drug-like” molecules were also tested successfully to demonstrate their potential applications in active pharmaceutical ingredient (API) synthesis. The tunability of the catalyst system enabled the matching of sterics and electronics of the ligand with that of the substrates to have desirable results for over five dozen systems in good yields and selectivity.