Synthesis of Fluorinated Quinolines and a Pyrazoloquinoline

Significance

The authors report on a one-pot procedure of the synthesis of 3-fluoro-4-(trifluoromethyl)quinolines C by sequential Mannich reaction of pentafluoropropen-2-ol B with aldimines A via a Friedel-Crafts ­cyclization/aromatization. Taking advantage of the presence of the CF₃ group, the resulting quinolines C were further converted into 3-substituted quinolines D using a range of heteroatom nucleophiles. In one case, quinoline C (R = Ph) was treated with hydrazine to lead efficiently to the pyrazoloquinoline E by overall elimination of three fluorides. Pentafluoropropen-2-ol was prepared in 60% overall yield by treatment of commercially available hexafluoro­acetone with Mg/TMSCl/DMF followed by reaction with concentrated H₂SO₄. The scope of all reactions was incompletely examined.