Friedel-Crafts acylation has been known since the 1870s, and it is an important organic synthetic reaction leading to aromatic ketone products. Friedel-Crafts acylation is usually performed with carboxylic acid chlorides or anhydrides, while amides are generally not useful substrates in these reactions. Despite being the least reactive carboxylic acid derivative, we have found a series of amides capable of providing aromatic ketones in good yields (55-96%, 17 examples). We propose a mechanism involving diminished C-N resonance through superelectrophilic activation and subsequent cleavage to acyl cations.
Friedel-Crafts acylation has been known since the 1870s, and it is an important organic synthetic reaction leading to n class="Chemical">aromatic ketone products. Friedel-Crafts acylation is usually performed with carboxylic acid chlorides or anhydrides, while amides are generally not useful substrates in these reactions. Despite being the least reactive carboxylic acid derivative, we have found a series of amides capable of providing aromatic ketones in good yields (55-96%, 17 examples). We propose a mechanism involving diminished C-N resonance through superelectrophilic activation and subsequent cleavage to acyl cations.
Authors: Marc Hutchby; Chris E Houlden; Mairi F Haddow; Simon N G Tyler; Guy C Lloyd-Jones; Kevin I Booker-Milburn Journal: Angew Chem Int Ed Engl Date: 2011-11-30 Impact factor: 15.336
Authors: Andrew E Ashley; Thomas J Herrington; Gregory G Wildgoose; Hasna Zaher; Amber L Thompson; Nicholas H Rees; Tobias Krämer; Dermot O'Hare Journal: J Am Chem Soc Date: 2011-08-24 Impact factor: 15.419
Authors: Marc Hutchby; Chris E Houlden; J Gair Ford; Simon N G Tyler; Michel R Gagné; Guy C Lloyd-Jones; Kevin I Booker-Milburn Journal: Angew Chem Int Ed Engl Date: 2009 Impact factor: 15.336