An Alternative Role for Acetylenes: Activation of Fluorobenzenes toward Nucleophilic Aromatic Substitution

Acetylenes are increasingly versatile functional groups for a range of complexity-building organic transformations and for the construction of desirable molecular architectures. Herein we disclose a previously underappreciated aspect of arylacetylene reactivity by utilizing alkynes as electron-withdrawing groups (EWG) for promoting nucleophilic aromatic substitution (S(N)Ar) reactions. Reaction rates for the substitution of 4-(fluoroethynyl)benzenes by p-cresol were determined by (1)H NMR spectroscopy, and these rate data were used to determine substituent (Hammett) constants for terminal and substituted ethynyl groups. The synthetic scope of acetylene-activated S(N)Ar reactions is broad; fluoroarenes bearing one or two ethynyl groups undergo high-yielding substitution with a variety of oxygen and arylamine nucleophiles.