Products with up to 99 % yield and up to 99 % ee were obtained in aza-Friedel-Crafts reaction of 1-naphthols and electron-rich phenols with isatin-derived ketimines using Cu(II) complex bearing binaphthyl-proline-imidazoline-based tridentate chiral ligand as catalyst. The system showed good scalability, and reaction carried out in gram-scale also provided the desired product in excellent ee.

Abstract

New chiral ligands could be obtained by introducing proline moieties and imidazoline moieties to binaphthyl skeletons. The chiral ligands exhibited balanced rigidity and flexibility which could allow the change of the conformations during the reactions on one hand, and could provide sufficient asymmetric induction on the other. The proline moiety could act as a linker connecting the binaphthyl skeletons and the imidazoline moieties as well as a coordinating group for the central metal, and the electronic and steric properties of the imidazoline groups could be carefully fine-tuned by the use of different substituents. In the presence of Cu(II) catalyst bearing such chiral ligands, aza-Friedel–Crafts reaction of 1-naphthols and electron-rich phenols with isatin-derived ketimines provided the desired products with good to excellent yields and up to 99 % ee. The reactions showed good scalability, and excellent ee could still be obtained when the reaction was carried out in gram-scale.