Design of C<sub>1</sub>-symmetric tridentate ligands for enantioselective dearomative [3 + 2] annulation of indoles with aminocyclopropanes.

Wang, Hai-Xia; Yang, Chun; Xue, Bai-Yu; Xie, Ming-Sheng; Tian, Yin; Peng, Cheng; Guo, Hai-Ming · Nat Commun · 2023

basic_science · Level V

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Abstract

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<sub>1</sub>-symmetric bifunctional tridentate imidazoline-pyrroloimidazolone pyridine ligand. Under 5 mol% of Ni(OTf)<sub>2</sub>-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<sub>2</sub>-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.