Transition-Metal-Mediated Nucleophilic Aromatic Substitution with Acids

Transition-metal-mediated
nucleophilic aromatic substitution (SNAr) reactions prefer
that a suitably strong nucleophile be
in an aprotic medium. Usually, using protic nucleophile/medium requires
high reaction temperatures (>180 °C) to overcome the attenuated
nucleophilicity for attack on the arene π system. Surprisingly,
we demonstrate herein a RhIII-mediated SNAr
reaction of a fluoroarene moiety with RCO2H (R = CH3, CF3) in acid media that proceeds at moderate
temperatures (<100 °C). We show both by experimental and with
DFT calculations that the mechanism proceeds through an internal nucleophilic
aromatic substitution (I-SNAr), where the nucleophile coordinates
to the metal ion prior to substitution, thereby mitigating
the acid influence.