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

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.