α,β-Disubstituted CF3-Enones as a Trifluoromethyl Building Block: Regioselective Preparation of Totally Substituted 3-CF3-Pyrazoles

An efficient pathway toward a novel class of trifluoromethyl building blocks was elaborated. The reaction of alpha-CF3-enamines with arylaldehydes resulted in direct synthesis of alpha,beta-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 alpha,beta-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.