Palladium-catalyzed fluoroalkylative C7–H cyclization of indoles to lilolidines

Abstract

Herein, we report a cooperative palladium and fluoroalkyl radical catalysis strategy that enables the direct C7–H functionalization/annulation of unactivated olefin-tethered N-alkyl indoles with bromofluoroalkyl reagents. This method provides efficient access to biologically relevant lilolidine-type fused skeletons. Utilizing readily available starting materials under mild conditions, this approach achieves high regioselectivity for the typically less reactive benzenoid C7 position, diverging from conventional C2-based cyclization paradigms. Mechanistic studies support a radical-mediated tandem cyclization pathway.