Faster initiation in the Friedel-Crafts reaction of benzyl fluorides using trifluoroacetic acid as activator

• The addition of trifluoroacetic acid drastically reduces the induction period.
• Lower reaction temperature is enabled.
• Milder conditions for benzylic fluorides bearing an electron-withdrawing group.

We report that the addition of a catalytic amount of trifluoroacetic acid (TFA) shortens the induction period associated with the 1,1,1,3,3,3-hexafluoroisopropoanol (HFIP)-promoted Friedel-Crafts reaction of benzylic fluorides. This faster initiation is due to TFA’s strong hydrogen-bond donation capability, not its Brønsted acidity. The improved reaction conditions were applied to a set of substrates, demonstrating how they could improve yields and reliability of this transformation.

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