Copper-Mediated Domino Cyclization/Trifluoromethylation/Deprotection with TMSCF3: Synthesis of 4-(Trifluoromethyl)pyrazoles

Abstract

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-CF₃ 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 (TMSCF₃) as the CF₃ source. The method can be applied to the synthesis of a 4-CF₃ analogue of the anti-inflammatory drug celecoxib.