Design of C1-symmetric tridentate ligands for enantioselective dearomative [3+2] annulation of indoles with aminocyclopropanes

Chiral polycyclic indolines are widely present in natural products and have become the focus of extensive synthetic efforts. Here, we show the catalytic asymmetric dearomative [3 + 2] annulation of indoles with donor-acceptor aminocyclopropanes to construct tricyclic indolines. Key to the success of the reaction is the rational design of C-1-symmetric bifunctional tridentate imidazoline-pyrroloimidazolone pyridine ligand. Under 5 mol% of Ni(OTf)(2)-ligand complex, diverse tricyclic indolines containing cyclopentamine moieties are obtained in good chemoselectivities, high diastereoselectivities, and excellent enantioselectivities. An unusual cis-configuration ligand is superior to the trans-configuration ligand and the corresponding C-2-symmetric tridentate nitrogen ligands in the annulation reaction. Mechanistic studies by control experiments and density functional theory calculations reveal a dual activation manner, where Ni(II) complex activates the aminocyclopropane via coordination with the geminal diester, and imidazolidine NH forms a H-bond with the succinimide moiety. Polycyclic indolines are valuable skeletons in drug discovery. Here, the authors report an asymmetric dearomative [3 + 2] annulation of indoles with aminocyclopropanes to construct tricyclic indolines.