Synthesis of Fluorinated Alkyl Aryl Ethers by Palladium-Catalyzed C-O Cross-Coupling.
Szpera R., Isenegger PG., Ghosez M., Straathof NJW., Cookson R., Blakemore DC., Richardson P., Gouverneur V.
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.