Acid–solvent cluster-catalyzed general and regioselective Friedel–Crafts arylation of alcohols

Abstract

Friedel–Crafts alkylation is among the oldest and most efficient strategies for C–H functionalization of arenes with a profound impact in both academia and industry. Despite significant advancements over the past 140 years, the extremely poor regioselectivity has greatly limited the broad application of the reaction. Herein, we disclose a general and highly regioselective Friedel–Crafts alkylation catalyzed by trifluoromethanesulfonic acid–hexafluoroisopropanol clusters, thereby providing various di- or polysubstituted arenes that previously were inaccessible or required elaborate synthetic efforts. Control experiments combined with DFT calculations suggest that the reaction involves a remarkable S_N1-type event and the use of acid–solvent clusters is the key factor in achieving regioselectivity.