Acid–Solvent Cluster-Promoted General and Regioselective Friedel–Crafts Acylation with Carboxylic Acids

Carboxylic acids are considered to be the most ideal acylating reagents for Friedel-Crafts acylation. However, the low electrophilicity of carboxylic acids and the ability of their byproduct water to deactivate Lewis and Brønsted acids greatly limit their application in this reaction. In this work, we developed a general and regioselective Friedel-Crafts acylation with carboxylic acids, wherein unactivated/activated arenes and various aromatic and aliphatic carboxylic acids were viable starting materials. Key to this accomplishment is the use of trifluoromethanesulfonic acid-hexafluoroisopropanol clusters.