Pd-Catalyzed Asymmetric Larock Indole Synthesis to Access Axially Chiral N-Arylindoles

Larock indole synthesis is one of the most straightforward and efficient methods for the synthesis of indoles; however, there has been no asymmetric version yet for the construction of indole-based axially chiral N-arylindoles since its initial report in 1991. Herein we report the first example of an asymmetric Larock indole synthesis by employing a chiral sulfinamide phosphine (SadPhos) ligand (Ming-Phos) with palladium. It allows rapid construction of a wide range of axially chiral N-arylindole compounds in good yields up to 98:2 er. The application of this unique chiral scaffold as an organocatalyst is promising. Furthermore, a kinetic study has revealed that the alkyne migratory insertion is the rate-determining step, which has been proven by the density functional theory (DFT) calculations. Additionally, DFT studies also suggest that the N–C dihedral difference caused by the steric hindrance of the ligand contributes to enantioselectivity control.