Friedel–Crafts Coupling of Electron-Deficient Benzoylacetones Tuned by Remote Electronic Effects

Acid-catalyzed electrophilic aromatic substitution for C–C bond formation, commonly referred to as the Friedel–Crafts reaction in recognition of its discoverers, has been one of the most useful reactions in organic chemistry for over a century. However, the Friedel–Crafts reaction cannot occur on a benzene ring having a strongly electron withdrawing group, such as an acyl group, which deactivates the aromatic ring toward electrophilic substitutions and remains a major challenge. Herein, the synthesis of naphthoquinones and 1,3-indandiones, bearing two acyl groups at positions ortho to each other on a benzene ring, are demonstrated by means of copper-catalyzed intramolecular aerobic oxidative acylation of benzoylacetone derivative precursors. This unusual Friedel–Crafts reaction reveals a new activation mode for the in situ polarity reverse of an electron-deficient aromatic ring to a reactive, electron-rich ring tuned by remote electronic effects.