Regioselective Synthesis of Functionalized 3- or 5‑Fluoroalkyl Isoxazoles and Pyrazoles from Fluoroalkyl Ynones and Binucleophiles

A facile
synthetic route toward either 3- or 5-fluoroalkyl-substituted
isoxazoles or pyrazoles containing an additional functionalization
site was developed and applied on a multigram scale. The elaborated
approach extends the scope of fluoroalkyl substituents for introduction
into the heterocyclic moiety, and uses convenient transformations
of the side chain for incorporation of fluoroalkyl-substituted azoles
into the structures of biologically active molecules. The utility
of the obtained building blocks for isosteric replacement of alkyl-substituted
isoxazole and pyrazole was shown by the synthesis of fluorinated Isocarboxazid
and Mepiprazole analogues.