Highly electronically deactivated benzylic alcohols, including those with a CF group adjacent to the OH-bearing carbon, undergo dehydrative Friedel-Crafts reactions upon exposure to catalytic Brønsted acid in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) solvent. Titration and kinetic experiments support the involvement of higher order solvent/acid clusters in catalysis.

A general, Brønsted acid catalyzed method for the room temperature, nucleophilic ring opening of donor-acceptor cyclopropanes in fluorinated alcohol solvent, HFIP, is described. Salient features of this method include an expanded cyclopropane scope, including those bearing single keto-acceptor groups and those bearing electron-deficient aryl groups. Notably, the catalytic system proved amenable to a wide range of nucleophiles including arenes, indoles, azides, diketones, and alcohols.

We report catalytic conditions for the direct substitution of arenes with numerous classes of alcohols and epoxides that were not previously accessible-all without pre-activation of either reaction partner. Furthermore, since the products of epoxide substitution are alcohols, this discovery enables the direct substitution of epoxides with two different arenes in one pot. The key to the reactivity relies on the fluorinated solvent hexafluoroisopropanol, which dramatically lowers kinetic barriers.