A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

Abstract

In-situ-generated N-aryl nitrile imines derived from trifluoroacetonitrile efficiently react with polycyclic 1,4-quinones, yielding fused pyrazole derivatives as the exclusive products. The reactions proceed via the initially formed [3 + 2]-cycloadducts, which undergo spontaneous aerial oxidation to give aromatized heterocyclic products. Only for 2,3,5,6-tetramethyl-1,4-benzoquinone, the expected [3 + 2]-cycloadduct exhibited fair stability and could be isolated in moderate yield (53%). The presented method offers a straightforward access to hitherto little known trifluoromethylated polycyclic pyrazoles. All products were isolated as pale colored solids with medium-intensity absorption maxima in the range of 310–340 nm for naphthoquinone-derived products and low-intensity bands in the visible region (≈400 nm) for the anthraquinone series.

Fluorinated and Non-Fluorinated 1,4-Diarylpyrazoles via MnO2-Mediated Mechanochemical Deacylative Oxidation of 5-Acylpyrazolines

“…Based on additional experiments, a mechanistic scenario comprising acyl-transfer onto the surface of heterogeneous oxidant was proposed. The presented results extend the scope of the previously reported method for the synthesis of the title compounds in organic solvents [ 42 ] and supplements recent developments, both in the synthesis of pyrazoles [ 2 , 53 , 54 , 55 ] and the application of nitrile imines as building blocks for organic synthesis [ 17 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 56 , 57 , 58 , 59 ].…”

“…In a series of recent works, we and other groups have demonstrated fluorinated nitrile imines of type 1 and C=C or C≡C dipolarophiles as superior reaction partners for the efficient preparation of fluoroalkylated pyrazole and pyrazoline derivatives. For example, electron-rich enamines [ 33 ], vinyl ethers [ 34 ], alkoxyallenes [ 35 ], and benzynes [ 36 ], as well as electron-deficient nitro- [ 37 ] and cyanoalkenes [ 38 ], isoxazolidinediones [ 39 ], quinones [ 40 ], and ynone derivatives [ 41 ] have served as dipolarophilic agents. Exemplary reactions leading to polysubstituted pyrazoles 2 – 4 and bicyclic analogues 5 (indazoles) are depicted in Scheme 1 a.…”

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

“…The [3 + 2] cycloaddition reactions are considered among the most powerful tools for the synthesis of versatile fluoroalkylated pyrazoles. Enol ethers, 1,4-naphthoquinones, o-trimethylsilylphenyl triflate and chalcones have all been reacted with fluorinated nitrile imines to give a series of fluoroalkylated pyrazoles by Jasiński's team [67][68][69][70][71][72] (Scheme 11a). Moreover, the trifluoromethylated 1,2,4-triazoles were synthesized with excellent regioselectivities in [3 + 2] cycloaddition reactions of trifluoromethylated hydrazonoyl chlorides with imidates, amidine and 1H-benzo[d]imidazole-2-thiols, all of which were individually reported by Wang, Deng and Cai, respectively [77][78][79] (Scheme 12a).…”

Trifluoromethylated 4,5-Dihydro-1,2,4-triazin-6(1H)-ones via (3+3)-Annulation of Nitrile Imines with α-Amino Esters

“…In this case, the final product is produced via the spontaneous elimination of an alcohol molecule from the initially formed (3+2)-cycloadduct. Further studies on 1,3-dipolar cycloadditions of 1 onto C=C and C≡C bonds using nitroolefins [ 33 ], cyanoalkenes [ 34 ], enones [ 35 , 36 , 37 ], alkoxyallenes [ 28 ], and benzynes [ 30 ] as dipolarophiles also evidenced the high synthetic potential of CF 3 -nitrile imines in the synthesis of pyrazoline and pyrazole derivatives. The addition of 1 with hetero-dipolarophiles are also known ( Scheme 1 b); a series of thiocarbonyl compounds including (cyclo)aliphatic [ 26 , 38 ], aromatic, and ferrocenyl thioketones [ 25 ], as well as thiochalcones [ 39 ] and thioamides [ 40 ], smoothly reacted with trifluoroacetonitrile imines 1 to afford 1,3,4-thidiazole derivatives of type 3 formed as the exclusive products.…”