α,β-Disubstituted CF<sub>3</sub>-Enones as a Trifluoromethyl Building Block: Regioselective Preparation of Totally Substituted 3-CF<sub>3</sub>-Pyrazoles
Vasiliy M. Muzalevskiy, Zoia A. Sizova, Vasiliy V. Panyushkin, В. А. Чертков, Victor N. Khrustalev, Valentine G. Nenajdenko
Abstract
An efficient pathway toward a novel class of trifluoromethyl building blocks was elaborated. The reaction of α-CF3-enamines with arylaldehydes resulted in direct synthesis of α,β-diaryl-CF3-enones isolated in up to 93% yield as E-isomers. The possible reaction mechanism was proposed using the Zimmerman–Traxler model. The reaction of α,β-diaryl-CF3-enones with hydrazines opens a novel pathway to trifluoromethylated pyrazolines. Oxidation of pyrazolines with DDQ opened access to totally regioselective preparation of 3-CF3-pyrazoles isolated in high yield. Using this strategy, 4-arylated derivatives of known drugs Celebrex, Mavacoxib, and SC-560 can be synthesized.