Photoredox-Catalyzed Radical Hexafluoroisopropoxylation of Arenes and Heteroarenes

Abstract

The hexafluoroisopropoxy group is a unique and underexplored fluoroalkoxy motif featuring distinctive conformational, electronic, and lipophilic properties. Herein, we report a visible-light-induced C–H hexafluoroisopropoxylation of (hetero)arenes employing a bench-stable N-hexafluoroisopropoxy benzotriazole as the hexafluoroisopropoxy radical precursor. This protocol enables the efficient construction of hexafluoroisopropyl aryl ethers under mild conditions, and is compatible with a broad range of aryl and heteroaryl substrates as well as synthetically and pharmacologically relevant functional groups. Mechanistic studies suggest that photoreductive cleavage of the hexafluoroisopropoxylating reagent by the excited photocatalyst generates the ·OCH(CF3)2 radical.