Palladium-Catalyzed Asymmetric Intramolecular Dearomative Heck Annulation of Aryl Halides to Furnish Indolines

An
unprecedented Pd-catalyzed asymmetric intramolecular cascade
cyclization of aryl halides with readily available arylboronic acids
proceeds through a Heck-type dearomative cyclization terminated with
arylation in the presence of Pd2(dba)3 (10 mol
%), Cu2O (5 mol %), and Cs2CO3 (2.0
equiv) in 1,2-dichloroethane (1.0 mL) at 100 °C for 15 h in air
using BINOL-based phosphoramidite as the chiral ligand. This dearomative
Heck protocol, which tolerates a broad variety of functional groups,
is amenable to the generation of optically active indoline derivatives
bearing all-carbon quaternary stereogenic centers in one step in moderate
to excellent yields, with excellent diastereoselectivities (>20:1)
and enantioselectivities (up to >99% ee). It is worth mentioning
that
no decrease in the enantiopurity of the indoline derivatives was observed
during the synthetic transformations of the products.