Cu-Catalyzed regioselective synthesis of functionalized 4-benzoyl-5-cyanopyrazoles under mild conditions

The unsaturated cyanocarbonyl compounds provide an attractive entry into electron-deficient dienophiles employed in Diels–Alder cycloadditions.1 To prepare these valuable substrates, several synthetic methodologies have been reported, including Wittig-type olefination of glyoxal derivatives, palladium catalyzed four-step procedure from alkenals, dehydrohalogenation of suitable substituted precursors, or five-step chemical modification of trans-styrylacetic acid.2 These approaches are frequently long and cumbersome. To the best of our knowledge, there is no report regarding either in situ generation of benzoylacrylonitriles, or employing them as dipolarophile in the 1,3-dipolar cycloaddition reactions. We have described an unprecedented copper catalyzed regioselective synthesis of 4-arylcarboxo-1-phenyl-3-aryl-1H-pyrazole-5-carbonitriles via the [3 + 2] cycloaddition reaction between phenacylmalononitriles and hydrazonoyl chlorides (Figure 1). 13C NMR spectra provide a useful clue to distinguish the product from its regioisomer. Thus, the ipso carbon to the cyano group in regioisomer is expected to appear below 100 ppm in 13C NMR spectra while the ipso carbon to the CN group in the product is expected to appear at about 140 ppm. In line with the studies conducted in our research group centralized on the synthesis of different substituted pyrazoles,3 we decided to carry out the multisubstituted pyrazole synthesis with the concomitant in situ generation of the dipole and the dipolarophile.

Keywords:

4-Benzoyl-5-cyanopyrazoles , Copper catalysis , [3+2] Cycloaddition , Phenacylmalononitrile , Hydrazonoyl chloride