C3-Symmetric tris(binaphthyl) phosphite ligands: Correlation of structural properties with performance in enantioselective palladium and gold catalysis

Five new C3-symmetric tris(binaphthyl) phosphites with different substituents at the binaphthyl 2' positions were synthesized and tested as ligands in palladium-catalyzed asymmetric Suzuki-Miyaura coupling reactions and gold-catalyzed asymmetric intramolecular hydroamination of allenes. The nature of the 2' -substituent had a strong effect on yields and enantioselectivities in both reactions, with phosphites bearing CF3-substituted aryl groups performing best and giving up to 52-53% ee. Crystal structures of two phosphites and three gold(I) phosphite complexes were obtained, and the latter revealed highly encumbered chiral steric pockets around the metal center that are enforced by the presence of 2'-aryl substituents. A diffusion-ordered spectroscopy (DOSY NMR) study suggested that the ligands undergo dynamic conformational processes in solution but become more rigid upon binding to a metal. X-ray and DFT-calculated structures supported the hypothesis that intramolecular CF3-pi interactions between neighboring 2'-aryl group on the ligands further rigidify their conformations, stabilizing the encumbered, C3-symmetric steric environment surrounding the catalytic metal center and thus increasing chiral induction for phosphites with CF3-containing 2'-aryl groups.