Palladium-catalyzed phosphonylation of pyrazoles substituted by electron-withdrawing groups

Solvent- and Metal-Controlled Regiodivergent Synthesis of Tri­fluoromethylated Pyrazol-3-yl- and Pyrazol-5-ylphosphonates

“…The structure of two isomeric trifluoromethylated pyrazolylphosphonates was proved by 13 C NMR. The 13 C spectra of 3a and 5a exhibit the following characteristic signals: a quartet of doublets at 143.0 ppm with 2 JC,F = 38.9 Hz and 3 JC,P = 17.4 Hz (3a, C-3), a doublet at 114.8 ppm with 2 JC,P = 18.6 Hz (3a, C-4), a doublet at 134.8 ppm with 1 JC,P = 216.6 Hz (3a, C-5), a doublet at 143.1 ppm with 1 JC,P = 233.7 Hz (5a, C-3), a doublet at 114.2 ppm with 2 JC,P = 23.5 Hz (5a, C-4), a quartet of doublets at 134.0 with 2 JC,F = 40.2 Hz and 3 JC,P = 9.0 Hz (5a, C-5), which are in good agreement with the proposed structures of 3a and 5a.…”

“…Flash chromatography was performed on silica gel using petroleum ether and ethyl acetate (EtOAc) as eluents. 1 H, 13 C, 19 F, and 31 P NMR spectra were recorded on 400 MHz spectrometers. Chemical shifts (ppm) were recorded using the solvent signal as the internal standard (CHCl3, 1 H NMR 7.26 ppm, 13 C NMR 77.16 ppm).…”

“…In this context, many procedures aimed at the synthesis heterocyclic compounds containing both substituents were developed over the last decade, including procedures to produce quinolines, 8 indolines 8d , imidazo[1,2-a]pyridines, 9 pyrazolo[1,5-a]pyridines, 10 etc. 11 However, to the best of our knowledge, the examples of the synthesis of trifluoromethylated pyrazolylphosphonates are limited by only two synthetic approaches: the reaction of ethyl diazoacetate with diethyl 3,3,3-trifluoroprop-1-ynylphosphonate to produce a mixture of regioisomers (Figure 1, a) 12 and Pd-catalyzed phosphonylation of 5-bromo-3-(trifluoromethyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole (b), 13 and general approaches to the synthesis of both isomeric trifluoromethylated N-substituted pyrazolylphosphonates are currently absent in the literature. Reactions whereby HX-type compounds are added to unsaturated carbon-carbon bonds have a great value in modern chemistry because of their atom economy, efficiency and low waste.…”

Pyrazole Bearing Molecules as Bioactive Scaffolds: A Review

“…Indeed, Phenazone was the first pyrazole which was commercially available as antipyretic agent [12]. Now the fascinating medicinal potential of pyrazole could be analyzed by the lists of drugs available in market such as; Celecoxib [13], Lonazolac [14], Mepirizole [15], Rimonabant [16], acomplia [17] Cimetidine [18], Fipronil [19], Dexacoxib [20], etc.…”

The reductive decyanation reaction: an overview and recent developments

“…Many strategies in organic synthesis involve the removal of a beneficial functional group. The electron-withdrawing properties of the nitrile functional group appear beneficial in a variety of reactions [ 1 – 2 ]. This group coordinates metal complexes and can be used as a directing group for C–H bond activation reactions catalyzed by transition metals [ 3 – 6 ].…”