Chiral Phosphoric Acid-Catalyzed Asymmetric Allylic Dearomatization of Tryptamines with Alkoxyallenes

Abstract

Abstract Catalytic asymmetric dearomatization of tryptamines has emerged as a powerful strategy for constructing chiral pyrroloindoline frameworks, which are ubiquitous in bioactive natural products. Despite tremendous advances in transition-metal-catalyzed synthesis of allyl-substituted pyrroloindolines, organocatalytic approaches remain elusive. Herein, we report a chiral phosphoric acid-catalyzed asymmetric allylic dearomatization of tryptamines with alkoxyallenes. This protocol features mild conditions and a broad substrate scope, delivering chiral pyrroloindolines in good yields (up to 93% yield) with stereoselectivity (up to >19:1 E/Z, 99% ee). Mechanistic studies suggest that a covalent adduct forms between the alkoxyallene and the chiral phosphoric acid. This catalytic system demonstrates a transformation of alkoxyallenes and offers a metal-free approach to access enantioenriched allyl-substituted pyrroloindolines, with significant potential for the synthesis of structurally diverse alkaloids.