Photomediated Hexafluoroisopropoxylation of Unactivated Aryl Halides

The use of fluoroalkoxy groups, such as trifluoromethoxy and 2,2,2‐trifluoroethoxy groups, in pharmaceutical and agrochemical development has increased dramatically in recent years. However, hexafluoroisopropoxy groups have remained significantly underrepresented, presumably due to limited synthetic methods for accessing this substituent in good yields. Herein, we report a mild, photochemical nucleophilic aromatic substitution (SNAr) approach for the synthesis of hexafluoroisopropyl aryl ethers from unactivated and abundant aryl halides. Notably, aryl chloride and bromide functionality are efficiently engaged by this methodology in addition to the traditional aryl fluoride nucleofuge. This method provided access to a diverse array of hexafluoroisopropyl aryl ethers, including multiple examples of late‐stage functionalization of active pharmaceutical ingredients. A simple flow system was adapted for 10x scale‐up, maintaining good yield for the reaction. Initial mechanistic studies indicate single electron oxidation of the arene as a key step in product formation.