Palladium-Catalyzed Direct C7 Trifluoromethylative Annulation of N -Homoallyl Indoles to Trifluoromethylated Lilolidines

Abstract

We report a cooperative palladium/trifluoromethyl radical strategy for directing-group-free C7-selective trifluoromethylative cyclization of N-homoallyl-2-substituted indoles using Togni-I reagent. This mild, one-step protocol constructs medicinally valuable trifluoromethylated lilolidine (pyrrolo[3,2,1-ij]quinoline) frameworks from readily accessible starting materials. The reaction selectively functionalizes the benzenoid C7 position, overriding indole’s innate C2 cyclization bias, shows good compatibility with a range of functional groups, and is amenable to gram-scale synthesis.