Triflic Anhydride‐Mediated Friedel–Crafts Arylation of Quinazolin‐4(3<i>H</i>)‐ones

Since the initial report, the Friedel-Crafts reaction has become a powerful tool to functionalize arenes. Nevertheless, the use of nitrogen heterocycles as electrophiles in Friedel-Crafts reactions has been less explored. Here, we show a Friedel-Crafts-like reaction of electron-rich arenes with quinazolin-4(3H)-ones, enabling late-stage C2-H arylation of quinazolin-4(3H)-ones via triflic anhydride (Tf₂O) activation. A series of substrates can be efficiently coupled under mild reaction conditions, affording C(sp³)-C(sp²) coupling product 2-aryl dihydroquinazolinones that can be further converted into the corresponding quinazolinone in the presence of base. This methodology offers efficient access to 2-aryl quinazolin-4(3H)-ones and exhibits good functional group compatibility and site selectivity. Mechanistic investigations reveal the formation of highly electrophilic iminium intermediates upon Tf₂O activation of quinazolin-4(3H)-ones, which serve as the key reactive species, enabling the Friedel-Crafts reaction to proceed efficiently.