ω-(3-Trifluoromethylpyrazol-4-yl)alkanoic acids via (3 + 2)-cycloaddition of nitrile imines with cyclic enones and deacylative aromatization

Abstract

A series of ω-substituted alkanoic acids functionalized with 1-aryl-3-trifluoromethylpyrazol-4-yl group was synthesized via two-step protocol using in situ generated CF₃-nitrile imines and cyclic enones as key building blocks. The first 1,3-dipolar cycloaddition step proceeded in a fully selective manner either in solutions or under solvent-free mechanochemical activation. Treatment of the first formed cycloadducts derived from 2-cyclopentenone or 2-cyclohexenone with DDQ afforded corresponding bicyclic pyrazoles formed via dehydrogenative oxidation pathway, whereas MnO₂-mediated deacylative aromatization led to desired propionic or butyric acid derivatives, respectively. In contrast, oxidation of model 2-cycloheptenone-derived (3 + 2)-cycloadduct yielded bicyclic analogue irrespectively to the applied conditions.