Cooperative Friedel-Crafts Alkylation of Electron-Deficient Arenes via Catalyst Activation with Hexafluoroisopropanol

A Friedel-Crafts alkylation of electron-deficient arenes with aldehydes through '' catalyst activation '' is presented. Through hydrogen bonding interactions, the solvent 1,1,1,3,3,3, -hexafluoroisopropanol (HFIP) interacted with the added Bronsted acid catalyst pTSA center dot H2O, increasing its acidity. This activated catalyst enabled the Friedel-Crafts alkylation of electron-neutral as well as electron-deficient arenes. Strongly electron withdrawing arenes including arenes with multiple halogen atoms, NO2, CHO, CO2R, and CN, groups acted as efficient nucleophiles in this reaction. DFT studies reveal multiple roles of solvent HFIP viz; increasing the Bronsted acidity of the catalyst pTSA center dot H2O, and stabilization of the transition states through a concerted pathway enabling the challenging reaction.