Synthesis of substituted benzofurans and indoles by Zn-catalyzed tandem Sonogashira-cyclization strategy

Abstract

Transition metal catalyzed cross-coupling reactions are one of the predominant strategies for the construction of heterocyclic structures which possess wide applications in the synthesis of natural products, pharmaceuticals, polymers, etc. Due to the vast importance of substituted benzofurans and indoles, numerous synthetic methodologies have been introduced for their synthesis. Among these methods, transition metal catalyzed cyclization reactions possess a unique position. In this manuscript, we disclose the first and efficient zinc-catalyzed protocol for the cyclization reactions of alkynes with 2-iodophenol and 2-iodoaniline leading to benzofurans and indoles respectively via a tandem Sonogashira coupling-cyclization process. Among the different metal catalysts, zinc has enormous potential due to its great availability, non-toxicity, eco-friendly and inexpensive nature.Zn(II) with N,N′-dimethylethylenediamine represents a suitable and efficient catalytic system for the desired tandem CC coupling-cyclization reactions, and a broad spectrum of functional groups are tolerated during the catalysis. A variety of substituted benzofurans and indoles have been successfully prepared in moderate to good yields under this new protocol.