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Ni-Catalyzed Reductive Coupling of Alkynes and Amides to Access Multi-Functionalized Indoles

Kwan Hong Min, Naeem Iqbal and Eun Jin Cho*

*Department of Chemistry, Chung-Ang University, 84 Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea, Email: ejchocau.ac.kr

K. H. Min, N. Iqbal, E. J. Cho, Org. Lett., 2022, 24, 989-994.

DOI: 10.1021/acs.orglett.1c03971


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Abstract

A nickel-catalyzed reductive coupling of alkynes and amides, followed by base-free transmetalation provides highly functionalized indoles comprising biologically important trifluoromethyl groups and challenging electron-rich alkenyl groups. The reaction proceeded selectively in the presence of an uncommon bidentate primary aminophosphine ligand.

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proposed reaction pathway



General experimental procedure for the preparation of indole derivatives

In an argon-filled glovebox, an oven-dried 20-mL resealable reaction tube equipped with a magnetic stir bar was charged with 2-alkynylphenyl trifluoroacetamide derivative (0.5 mmol), arylboronic acid (2.0 equiv., 1 mmol), Ni(COD)2 (3 mol%), apPhos (4 mol%), and TFE (0.1 M, 5 mL). The reaction tube was then sealed with a screw-cap, taken out of the glove box, and placed into a preheated oil bath at 80 C with stirring. After 1 h, the tube was removed from the oil bath and allowed to cool to room temperature. The reaction mixture was concentrated in vacuo, and purified by flash column chromatography using hexane/EtOAc as the eluent to afford the corresponding indole product derivative.


Key Words

indoles


ID: J54-Y2022