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

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 ·H 2 O 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.