Issue 36, 2022

Oxidatively induced reactivity in Rh(iii)-catalyzed 7-azaindole synthesis: insights into the role of the silver additive

Abstract

A typical synthetic protocol for preparing 7-azaindoles involves the coupling of 2-aminopyridine and alkyne substrates using a Rh(III)-catalyst. The catalysis requires the assistance of an external Ag+ oxidant that is thought to regenerate the catalyst and increase the turnover efficiency. Density functional theory (DFT) simulations confirm that Ag+ can oxidize various neutral Rh(III) intermediates encountered at different stages of the catalysis. Among them, the catalytically relevant species is a cationic Rh(III)-pyridyl+ complex (2A), which undergoes C–H activation of pyridine and couples an internal alkyne substrate into the pyridyl ligand to form the desired 7-azaindole product. Computations reveal that the oxidation also accelerates the reaction steps, including C–H activation via concerted metalation deprotonation (CMD), 1,2-alkyne insertion, and reductive elimination, thus highlighting the role of Ag+ as a catalytic promoter for the oxidatively induced reactivity of the Rh-catalyst in 7-azaindole synthesis. DFT calculations show that the catalysis is inefficient without invoking an oxidatively induced reaction pathway.

Graphical abstract: Oxidatively induced reactivity in Rh(iii)-catalyzed 7-azaindole synthesis: insights into the role of the silver additive

Supplementary files

Article information

Article type
Edge Article
Submitted
22 mar. 2022
Accepted
17 ago. 2022
First published
31 ago. 2022
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2022,13, 10707-10714

Oxidatively induced reactivity in Rh(III)-catalyzed 7-azaindole synthesis: insights into the role of the silver additive

H. Ryu, B. Pudasaini, D. Cho, S. Hong and M. Baik, Chem. Sci., 2022, 13, 10707 DOI: 10.1039/D2SC01650H

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