Enantioselective intramolecular Pictet–Spengler type annulation of indole-linked 3-methyleneisoindolin-1-ones

Abstract

An enantioselective intramolecular Pictet–Spengler type annulation of indole-linked 3-methyleneisoindolin-1-ones was developed by using a chiral phosphoric acid as a catalyst. This method enabled the construction of a series of chiral isoindolinone fused tetrahydro β-carbolines in moderate to good yields (up to 97%) with moderate to good enantioselectivities (up to 96% ee). Furthermore, an α₁-AR antagonist was prepared by the reduction of one product. Thus a convenient procedure was provided to construct bioactive tetrahydro β-carbolines.