A rational pre-catalyst design for bis-phosphine mono-oxide palladium catalyzed reactionsElectronic supplementary information (ESI) available: Detailed experimental procedures and characterization data for all new compounds. CCDC 1512973-1512975. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc05472b

Significant catalyst loading reduction and increased reaction robustness have been achieved for a Pd-catalyzed asymmetric intramolecular C-N coupling through comprehensive mechanistic studies. Detailed kinetic, spectroscopic, and crystallographic analyses revealed that the mono-oxidation of the bis-phosphine ligand is critical for a successful transformation. 31 P NMR studies provided an understanding of the inefficient activation of the Pd(OAc) 2 /( R , R )-QuinoxP* pre-catalyst to form the active bis-phosphine mono-oxide-Pd(0) catalyst with competitive formation of a less active ( R , R )-QuinoxP*·PdBr 2 complex. Based on these detailed mechanistic studies, a new series of bis-phosphine mono-oxides (BPMO)-ligated Pd( ii ) pre-catalysts have been rationally developed that allow for reliable and complete catalyst activation which should have general utility in academic and industrial settings. Detailed mechanistic studies of a Pd-catalyzed asymmetric C-N coupling led to a rational design of a new series of bis-phosphine mono-oxides ligated Pd( ii ) pre-catalysts that allow for reliable and complete catalyst activation.