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

A series of chiral, C3-symmetric tris(binaphthyl) phosphite ligands was synthesized and tested in palladium-catalyzed asymmetric Suzuki-Miyaura coupling reactions and gold-catalyzed asymmetric intramolecular hydroaminations of allenes. Enantioselectivity differences were attributed to variations in conformational rigidity based on crystallographic, DFT, and DOSY NMR analyses of differently substituted chiral phosphites and their gold complexes. [Display omitted] Five new C3-symmetric tris(binaphthyl) phosphites with different substituents at the binaphthyl 2ʹ 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 2ʹ-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 2ʹ-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-π interactions between neighboring 2ʹ-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 2ʹ-aryl groups.