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, the asymmetric sequential hydrofunctionalization cyclization, which could incorporate two functional groups across carbon-carbon multiple bonds to construct chiral complex cyclic compounds, has been only 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 to construct a broad spectrum of enantioenriched pyrido[1,2-α]indole 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.