Synthesis of Tetracyclic Indolines through Palladium-Catalyzed Asymmetric Dearomative reaction of Aryl Iodides

A palladium-catalyzed asymmetric intramolecular Heck reaction of aryl iodides with alkynyl carboxylic acids has been developed, delivering various indoline frameworks in moderate to excellent yields (up to 95 %) with excellent enantioselectivities (up to 96 % ee) and diastereoselectivities (>20 : 1) using BINOL-based phosphoramidite as chiral ligand. This cascade annulation protocol, which tolerates a broad variety of functional groups and is conducted under an argon atmosphere, provides efficient and atom-economical access to structurally diverse 2,3-disubstituted indolines bearing vicinal tertiary and quaternary stereocenters. Additionally, the synthetic products could be converted to useful unique indoline derivatives without loss of enantiomeric excess.

Automated summary

The described methodology provides an efficient and atom-economical approach to access structurally diverse 2,3-disubstituted indolines with vicinal tertiary and quaternary stereocenters. The cascade annulation protocol, using a palladium-catalyzed asymmetric intramolecular Heck reaction, demonstrates excellent yields and enantioselectivities, making it a promising method for the synthesis of unique indoline derivatives.