Cooperative Friedel–Crafts Alkylation of Electron‐Deficient Arenes via Catalyst Activation with Hexafluoroisopropanol**

Abstract

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 Brønsted acid catalyst pTSA•H₂ O, 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, CO₂ R, and CN, groups acted as efficient nucleophiles in this reaction. DFT studies reveal multiple roles of solvent HFIP viz; increasing the Brønsted acidity of the catalyst pTSA•H₂ O, and stabilization of the transition states through a concerted pathway enabling the challenging reaction.