Ruthenium-mediated nucleophilic aromatic substitution of hydrogen in benzene

Abstract

The direct functionalization of unactivated hydrocarbons remains a significant challenge in modern chemistry. In this study, we demonstrate that a simple ruthenium complex featuring a chelating tBuPN ligand can mediate the nucleophilic aromatic substitution of hydrogen (SNArH) in benzene. Key intermediates were kinetically trapped in low-temperature NMR experiments, providing crucial insights into the reaction mechanism. These findings are further supported by isotopic labeling and comprehensive DFT studies. The data shows that the substitution proceeds via an unprecedented mechanism, involving reversible rear-side nucleophilic addition of the exogenous nucleophile to the ruthenium-bound benzene, followed by an intramolecular hydride migration facilitated by deprotonation of tBuPN ligand. The broad range of nucleophiles amenable to this reaction, including classical non-nucleophilic bases, showcases the versatility of this reaction and makes it a promising candidate for further developments in the area of SNArH.

Graphical abstract: Ruthenium-mediated nucleophilic aromatic substitution of hydrogen in benzene

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Article information

Article type
Edge Article
Submitted
18 Mar 2025
Accepted
09 Jun 2025
First published
16 Jun 2025
This article is Open Access

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

Chem. Sci., 2025, Advance Article

Ruthenium-mediated nucleophilic aromatic substitution of hydrogen in benzene

S. Melnikov, D. Hwang, P. Gabbert, B. Park, M. Lutz, M. Baik and D. L. J. Broere, Chem. Sci., 2025, Advance Article , DOI: 10.1039/D5SC02090E

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