Synthesis of Fluorinated Alkyl Aryl Ethers by Palladium-Catalyzed C-O Cross-Coupling

Abstract

Herein, we report a highly effective protocol for the cross-coupling of (hetero)aryl bromides with fluorinated alcohols using the commercially available precatalyst ^tBuBrettPhos Pd G3 and Cs₂CO₃ in toluene. This Pd-catalyzed coupling features a short reaction time, excellent functional group tolerance, and compatibility with electron-rich and -poor (hetero)arenes. The method provides access to ¹⁸F-labeled trifluoroethyl ethers by cross-coupling with [¹⁸F]trifluoroethanol.