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

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.