A general approach for preparation of two types of polyfunctionalized 3-trifluoromethylpyrazoles is reported. The protocol comprises (3 + 2)-cycloaddition of the in situ generated trifluoroacetonitrile imines with enones leading to trans-configured 5-acyl-pyrazolines in a fully regio- and diastereoselective manner. Initially formed cycloadducts were aromatized by treatment with manganese dioxide. Depending on the solvent used, the oxidation step either led to fully substituted pyrazoles (DMSO) or proceeded via a deacylative pathway to afford 1,3,4-trisubstituted derivatives (hexane) with excellent selectivity.

Non-catalysed addition of trifluoroacetonitrile imines to enol ethers provided fully regioselectively (3 + 2)-cycloadducts, which either spontaneously or via Brønsted acid-induced elimination of ROH molecules led to the formation of 3-trifluoromethylated pyrazoles. In the case of 2,3-dihydrofuran, the respective bicyclic intermediate was isolated and its structure was confirmed by X-ray analysis. Using the developed protocol the synthesis of a known antitumor compound SC-560 was performed in 45% yield. Subsequent functionalisations of selected 4-(ω-hydroxyalkyl)pyrazoles at C(5) through lithiation/addition, cross-coupling reactions or via intramolecular Pd-catalysed C–H arylations opened up an access to polysubstituted pyrazoles including unusual tricyclic systems comprising 7-membered rings (oxepane, thiepane and azepane) as the central unit.

Dedicated to Professor Sławomir Jarosz (Warsaw) on the occasion of his 65^th birthday Fluorinated nitrile imines generated in situ from the corresponding fluoral-derived hydrazonoyl bromides smoothly react with monomeric aryl/hetaryl-substituted thiochalcones yielding 2,3-dihydro-1,3,4-thiadiazoles in a chemo- and regioselective manner. The elaborated protocol can be efficiently applied starting with precursors functionalized with both electron-donating and electron-withdrawing groups located at the para position of the aryl ring. In contrast, the non-fluorinated nitrile imines do not enter the (3+2)-cycloaddition reactions with title thiochalcones.