Ruthenium-mediated nucleophilic aromatic substitution of hydrogen in benzene

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 ^<i>t</i>BuPN ligand can mediate the nucleophilic aromatic substitution of hydrogen (S_NArH) 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 <i>via</i> 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 ^<i>t</i>BuPN 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 S_NArH.