Palladium-catalyzed asymmetric sequential hydroalkylation and hydroamination of 1,3-enynes with 3-hydroxyindoles

Abstract

Transition-metal catalyzed asymmetric hydrofunctionalization of unsaturated hydrocarbons has emerged as an efficient method to access diverse chiral value-added compounds. In contrast, asymmetric sequential hydrofunctionalization cyclization, which could incorporate two functional groups across carbon–carbon multiple bonds to construct chiral complex cyclic compounds, has only been sporadically explored. Herein, we report a palladium-catalyzed asymmetric sequential hydroalkylation and hydroamination of readily available 1,3-enynes with 3-hydroxyindoles. This redox-neutral process provides an efficient route for constructing a broad spectrum of enantioenriched pyrido[1,2-a]indoles and derivatives with high atom- and step-economy. Preliminary mechanistic investigations reveal that this transformation proceeds via an intermolecular enyne hydroalkylation pathway to produce an allene intermediate. Subsequent intramolecular hydroamination of the allene intermediate occurs via an axial-to-center chirality transfer process. Density functional theory (DFT) studies were conducted to probe the origin of enantioselectivities.