ABSTRACT
Azacycles such as indoles and tetrahydroquinolines are privileged structures in drug development. Reported here is an unprecedented regiodivergent intramolecular nucleophilic addition reaction of imines as a flexible approach to access N-functionalized indoles and tetrahydroquinolines, by the control of reaction at the N-terminus and C-terminus, respectively. Using ketimines derived from 2-(2-nitroethyl)anilines with isatins or α-ketoesters, the regioselective N-attack reaction gives N-functionalized indoles, while the catalytic enantioselective C-attack reaction affords chiral tetrahydroquinolines featuring an α-tetrasubstituted stereocenter. Mechanistic studies reveal that hydrogen-bonding interactions may greatly facilitate such unusual N-attack reactions of imines. The utility of this protocol is highlighted by the catalytic enantioselective formal synthesis of (-)-psychotrimine, and the construction of various fused aza-heterocycles.
