Cu-Mediated Tandem 2,3-Disubstituted Indole Synthesis from Simple Anilines and Internal Alkynes via C–H Annulation

Abstract

A simple, cost-effective, and straightforward method for the synthesis of 2,3-disubstituted indole scaffolds has been developed. The present protocol involves copper-mediated tandem hydroamination followed by C–H annulation of unprotected anilines with a wide range of internal alkynes. In the presence of Cu(OAc)2·H2O and trifluoroacetic acid (TFA), the reaction proceeds well to afford a variety of substituted indole derivatives in moderate to good yields. This process was found to be compatible with both primary and secondary anilines coupled with aromatic/aliphatic alkynes. High-purity copper nanoparticles can be recovered after the reaction, revealing the cost-effectiveness and environmentally benign feature of the current protocol.

Copper–Catalyzed Construction of the Indole Core: Recent Advancements

“…Copper–catalyzed annulation involving aromatic amines is a powerful strategy for synthesizing indole scaffolds. Recently, Bhanage's group devised a copper‐mediated tandem protocol for preparing functionalized indoles 3 from readily accessible anilines 1 and alkynes 2 [53] . Anilines bearing electron–donating and electron‐withdrawing substituents smoothly reacted with various alkynes in the presence of Cu(OAc) 2 and trifluoroacetic acid (TFA) to afford desired indoles in moderate to good yields (up to 72 %).…”