Transition-Metal-Mediated Nucleophilic Aromatic Substitution with Acids

Transition-metal-mediated nucleophilic aromatic substitution (S_NAr) 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 system. Surprisingly, we demonstrate herein a Rh^III-mediated S_NAr 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-S_NAr), where the nucleophile coordinates to the metal ion prior to substitution, thereby mitigating the acid influence.