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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 Bronsted acidity. The improved reaction conditions were applied to a set of substrates, demonstrating how they could improve yields and reliability of this transformation.

An effective process for the regioselective Tsuji—Trost reaction of 4,4,4-trifluorobut-2-ene derived carbonate (I) and (VI), or acetate (VII) with aromatic alcohols, secondary amines, and malonate type C-nucleophiles is developed.

A Friedel–Crafts benzylation of arenes with benzyl fluorides has been developed. The reaction produces 1,1-diaryl alkanes in good yield under mild conditions without the need for a transition metal or a strong Lewis acid. A mechanism involving activation of the CF bond through hydrogen bonding is proposed. This mode of activation enables the selective reaction of benzylic CF bonds in the presence of other benzylic leaving groups.

The presented method proceeds for a wide range of carboxylic acids and amines and without racemization [viz.

The procedure provides an efficient method to prepare a number of primary chlorides, bromides, and iodides.