A catalytic atroposelective Friedel–Crafts alkylation to access axially chiral C2-arylindoles via dynamic kinetic resolutions

Abstract

Indole-based atropisomers have emerged as an important backbone in drug discovery and novel catalyst/ligand design. However, the development of asymmetric synthesis of axially chiral 2-arylindoles is sluggish due to their very low rotation barrier. Herein, we developed an amine-catalyzed atroposelective F–C alkylation of rotation-free 2-arylindoles with α,β-unsaturated aldehydes via the DKR process. Various axially chiral 2-arylindoles were obtained with good results. Besides, a promising chiral phosphine was derived from the obtained atropisomers.