Synthesis of 2,3-Disubstituted Indoles via Palladium-Catalyzed Cyclization of ortho-Alkynyl Anilines

Key words

palladium catalysis - indole synthesis - anilines

Significance

Indoles are structural motifs found in a wide variety of natural products and pharmaceutical agents. While other palladium-catalyzed indole syntheses had been primarily focused on the cyclization of compounds containing pre-installed substituents of the desired indole, Cacchi and co-workers demonstrated a modular synthesis of 2,3-disubstituted indoles using a variety of 2-alkynyl anilines and aryl halides or vinyl triflates, stream­lining the synthesis of this class of compound.

Comment

The authors note that other bases such as triethylamine performed poorly compared to potassium carbonate. Similarly, indole products were not observed when employing aniline derivatives with a free amino group or acetamido group, highlighting the importance for a stronger electron-withdrawing group to be present on the nitrogen atom.

Publication History

Article published online:
16 June 2023