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. A novel, highly efficient, and practical protocol for the asymmetric synthesis of 2,3‐disubstituted indolines in the presence of BINOL‐based phosphoramidite (12 mol %), Pd(dba)2 (10 mol %), Cs2CO3 (2.0 equiv) in toluene (1.0 mL) at 100 °C for 15 h is described, starting from readily accessed aryl iodides with alkynyl carboxylic acids. A very wide range of 2,3‐disubstituted indolines bearing vicinal quaternary and tertiary stereocenters were efficiently constructed with excellent enantioselectivities (up to 96% ee) and diastereoselectivities (>20:1).