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.