Palladium-Catalyzed Enantioselective Intramolecular Heck Reaction to Access Chiral C3-Tertiary Indolines

Abstract

Chiral C3-tertiary indolines serve as crucial structural scaffolds in biologically active molecules and natural products. However, the asymmetric synthesis of such compounds remains largely underexplored. In this work, we report a palladium-catalyzed intramolecular Heck strategy that can override the intrinsic aromatization and enable selective access to enantiomerically enriched 3-(2-oxoethyl)indolines (up to 96% ee). The key to the success of this strategy is introducing a hydroxy group at the α-position of alkene moieties of N-allyl-2-iodoanilines, which undergo regioselective β-hydride elimination. We demonstrate the synthetic utility of this strategy by performing downstream transformations of the products based on aldehyde groups. Density functional theory (DFT) calculations elucidate the mechanism and stereoinduction.