Assembly of CF3-Pyrazole-Triazole Hybrids through (3 + 3)-Cycloaddition/Ring Contraction and Click Chemistry
Kamil Świątek1, Greta Utecht-Jarzyńska1, Barbara Olszewska1
1Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12, 91403 Łódź, Poland.
Abstract:
A concise three-step approach for the construction of trifluoromethylated pyrazole-1,2,3-triazole hybrids, considered a promising platform for the discovery of new pharmaceuticals and agrochemicals, is described. The sequence involves (i) (3 + 3)-cycloaddition of in situ-generated nitrile imines with mercaptoacetaldehyde followed by spontaneous ring contraction, (ii) a C(5)-selective azide transfer, and (iii) a copper-catalyzed Huisgen-Meldal-Sharpless click cycloaddition. The devised protocol enables the preparation of a broad array of target structures, including drug-inspired analogues and chiral representatives, obtained in moderate to high overall yields. Subsequent functional group interconversions on the hybrids provide access to synthetically valuable motifs such as aldehydes, amines, carboxylic acids, esters, and amide. The structure of a representative product was confirmed by X-ray analysis.
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