Sterically-controlled intermolecular Friedel-Crafts acylation with twisted amides via selective N-C cleavage under mild conditions

Highly chemoselective Friedel-Crafts acylation with twisted amides under mild conditions is reported for the first time. The reaction shows high functional group tolerance, obviating the need for preformed sensitive organometallic reagents and expensive transition metal catalysts. The high reactivity of amides is switched on by ground-state steric distortion to disrupt the amide bond n(N) -> pi(CO)* resonance as a critical design feature. Conceptually, this new acid-promoted mechanism of twisted amides provides direct access to bench-stable acylating reagents under mild, metal-free conditions.