Simple and expedient metal-free CH-functionalization of fluoro-arenes by the BHAS method – Scope and limitations

• Substitution of aromatic iodides with non-activated fluoroarenes through radical-promoted reaction conditions.
• Simple method to generate ‘FnAr’-substituted derivatives from a single haloarene synthetic intermediate.
• Relatively cheap and non-toxic fluoroarene substrates used directly from the bottle.

We report here the facile substitution of aromatic iodides with non-activated fluoroarenes through radical-promoted reaction conditions. Applying the recently-popularized BHAS methodology, catalytic 1,10-phenanthroline and KOtBu and the desired fluorobenzene as reactant and solvent, various fluorinated biaryls can be synthesized in moderate to good yields. The method provides a simple access to generate potentially many ‘FnAr’-substituted derivatives from a single haloarene synthetic intermediate, using relatively cheap and non-toxic fluoroarene substrates directly from the bottle, and may therefore be of use for medicinal chemistry campaigns. Although the method has a limitation in that it is not compatible with substrates featuring base-sensitive substituents, especially 1,4-difluorobiaryls are accessible in good yields. These investigations facilitate the exploitation of the potential of this protocol to synthesize biologically active fluorinated biaryls, e.g. WNT-active molecules.

A simple method to generate ‘FnAr’-substituted derivatives from a single haloarene synthetic intermediate, using relatively cheap and non-toxic fluoroarene substrates directly from the bottle is presented.Figure optionsDownload as PowerPoint slide