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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.

Two methods for the introduction of the (E)-3-(pentafluorosulfanyl)allyl chain unto various nucleophiles were investigated: a palladium-catalyzed Tsuji–Trost reaction of (E)-ethyl [3-(pentafluorosulfanyl)allyl]carbonate and a nucleophilic substitution reaction on (E)-[3-(pentafluorosulfanyl)allyl] 4-methylbenzenesulfonate. Various nucleophiles were examined including phenols, aliphatic and aromatic amines, aliphatic and aromatic thiols and malonates. Overall, the two approaches were found to be complementary as the Tsuji–Trost reaction worked better with phenols while the SN2 reaction generally provided better results with the amines. In addition, the sulfur-based product could only be obtained using the SN2 reaction while the malonates only worked under the Tsuji–Trost conditions.

A systematic study of the reactivity of ( E )-4,4,4-trifluorobut-2-en-1-yl 4-methylbenzenesulfonate towards different classes of nucleophiles (alcohols, amines, thiols and malonates) was performed. A single set of reaction conditions (with small variations) allowed the isolation of the substitution product in moderate to good yields for all the nucleophiles tested with the exception of benzyl alcohol and indole.

The Friedel-Crafts benzylation of arenes using benzyl alcohols activated in situ with XtalFluor-E is described. A wide range of 1,1-diarylmethanes and 1,1,1-triarylmethanes were prepared under experimentally simple and mild conditions, without the need for a transition metal or a strong Lewis acid. Notably, the reactivity observed demonstrates the potential of XtalFluor-E to induce C-OH bond ionization and SN1 reactivity of benzylic alcohols.

The racemic and enantioselective metal-catalyzed addition of arylboronic acids to 4- and 3-(pentafluorosulfur)benzaldehydes is reported. The racemic synthesis was accomplished using a Pd-based system and a wide range of arylboronic acids could be used, resulting in yields of 42 to 98% of the corresponding SF

The halogenation of primary alcohols is presented. The use of a combination of tetraethylammonium halide and [Et(2)NSF(2)]BF(4) (XtalFluor-E) allows for chlorination and bromination reactions to proceed efficiently (up to 92% yield) with a wide range of alcohols. Iodination reactions are also possible albeit in lower yields.

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 C-F bond through hydrogen bonding is proposed. This mode of activation enables the selective reaction of benzylic C-F bonds in the presence of other benzylic leaving groups.

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