Cobalt-Catalyzed Asymmetric Dearomative [3 + 2] Annulation of Quinolines, Isoquinolines, and Pyridines

Abstract

A highly enantioselective dearomative [3 + 2] annulation of quinolines, isoquinolines, and pyridines with donor− acceptor aminocyclopropanes was achieved. With C 1 -symmetric imidazoline-pyrroloimidazolone pyridine as the tridentate ligand and Co(OTf) 2 as the Lewis acid, diverse chiral indolizidine and benzo-fused indolizidine derivatives were obtained in good yields (up to 98% yield), excellent diastereoselectivities (>20:1 dr), and excellent enantioselectivities (up to 98% ee). Mechanistic experiments and density functional theory (DFT) calculations revealed that the tridentate nitrogen ligand acted as a bifunctional chiral ligand. The ligand not only coordinated with the Co(II) salt to activate aminocyclopropane via bidentate coordination, but also formed a H-bond with the oxygen atom in the succinimide moiety to fix the orientation of aminocyclopropane, thus facilitating the nucleophilic attack of N-heteroaromatics. Additionally, the high enantioselectivity of the reaction was governed by steric factors.

Phen-2NO, a new C2-symmetric rigid-featured tetradentate ligand, and its application in the asymmetric alkylation reaction of indoles

“…Based on the above experimental studies and previous works, 8,9 a – c ,13 a plausible reaction mechanism is presented (Scheme 7). L1a as a tetradentate ligand coordinated to Ni( ii ) via two oxygen and two nitrogen atoms.…”

Cobalt(II)-Catalyzed Enantioselective Propargyl Claisen Rearrangement: Access to Allenyl-Substituted Quaternary β-Ketoesters

“…The enantioselective para -Claisen rearrangement of naphthyl 1-propargyl ethers that employed the Co­(OTf) 2 - N , N ′-dioxide complex as a chiral catalyst, delivering dearomatized benzocyclohexenones bearing all-carbon quaternary stereocenters in excellent yields was also reported by Feng and co-workers later in 2022 . Recently, we developed a chiral tridentate imidazoline-pyrroloimidazolone pyridine (PyIPI) ligand and applied it for enantioselective dearomative [3 + 2] annulation of indoles with aminocyclopropanes . While working on our ongoing research endeavors in developing asymmetric catalysis promoted by a PyIPI-metal complex, we became interested in the enantioselective propargyl Claisen rearrangement of O -propargyl β-ketoesters, which could be applied for the synthesis of allenyl-substituted all-carbon quaternary β-ketoesters (Scheme d).…”

“…Based on the above experimental studies and previous work, , a possible stereochemical model was proposed (Figure ). In the favorable transition state, three nitrogen atoms of PyIPI L10 and two oxygen atoms of substrate 1a coordinate to Co­(II).…”

Asymmetric [3+n]‐Cycloaddition Reactions of Donor‐Acceptor Cyclopropanes

“…With C 1 -symmetric imidazoline-pyrroloimidazolone pyridine L7 as the tridentate ligand which acted as a bifunctional chiral ligand and Co(OTf) 2 as the Lewis acid, diverse chiral indolizidine and benzo-fused indolizidine derivatives 21 were obtained in good yields (up to 98 % yield), excellent diastereoselectivities (> 20 : 1 dr), and excellent enantioselectivities (up to 98 % ee) (Scheme 11). [35]…”