Copper-Mediated Domino Cyclization/Trifluoromethylation/Deprotection with TMSCF: Synthesis of 4-(Trifluoromethyl)pyrazoles.

A copper-mediated synthesis of 4-(trifluoromethyl)pyrazoles is described. In one step from readily accessible α,β-alkynic tosylhydrazones, a remarkable domino sequence of cyclization, trifluoromethylation, and detosylation takes place to furnish the 4-CF N-H pyrazole cores with good functional group compatibility. The reaction conditions are mild and convenient, at room temperature in air, using the commercially available trifluoromethyltrimethylsilane (TMSCF) as the CF source. The method can be applied to the synthesis of a 4-CF analogue of the anti-inflammatory drug celecoxib.