Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• to be the determining step for the enantioselectivity, while the diastereoselectivity is mainly induced by the chiral alkylated naphthol intermediate in the second annulation step (Scheme 46). Xu et al. [80] realized asymmetric [4 + 1] cyclization of yne-allylic esters with pyrazolones. This

• annulation mechanism. Dearomative annulation of phenols or 2-naphthols. Dearomative annulation of indoles. Postulated annulation step. Asymmetric [4 + 1] cyclization of yne-allylic esters with pyrazolones. Proposed mechanism. Construction of C–C axially chiral arylpyrroles. Construction of C–N axially chiral

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• microwave-assisted pseudo-five-component synthesis of tris(pyrazolyl)methanes 35, where first β-ketoesters and hydrazines form pyrazolones 36. One equivalent reacts in a Knoevenagel condensation with 4-formylpyrazole 34 to give pyrazolidine pyrazole 37, while the second equivalent undergoes a Michael

• hydrolactite catalysts (C-Mg-Al HAT-3) [90]. With β-ketoesters, the method can be extended to a four-component synthesis. Initially, β-ketoesters react with hydrazine to form pyrazolones, while a Knoevenagel reaction between malononitrile and aldehyde simultaneously generates a Michael system. Both

• -hydroxypyrazoles 143 and not tautomeric 3-pyrazolones. Alternative access to alkynones can be achieved by nucleophilic addition of lithiated alkynes to N-substituted phthalimides 145, followed by ring opening to give, upon the addition of water, the corresponding 3-hydroxyindolines. These intermediates are in

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• disclosed organocatalyzed [5 + 1] double Michael additions between pyrazolones and dienones (Scheme 1b) [23]. Very recently, the Chimni group reported a cinchona-derived squaramide-catalyzed 1,4-Michael addition reaction of pyrazolin-5-ones with 2-enoylpyridines (Scheme 1c) [24]. Recently, we developed an

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• , Yotphan and colleagues realized a direct thiocyanation of N-substituted pyrazolones under metal-free conditions [49]. Besides, Choudhury and co-workers developed an additive and metal-free methodology for the C–H thiocyanation of aminopyrazoles, using H2O2 as a benign oxidizing agent (Scheme 1b) [41]. Pan

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• spot” to illustrate the existence of such “white area”. When considering pyrazolones with the general formula A depicted in Scheme 1, these are very easy to prepare in one step using a Knorr condensation. Whereas, up to 2006, an order of magnitude less of the isomeric derivatives B had been reported in

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• various pyrazolones. Enantioselective and atroposelective synthesis of axially chiral N-arylcarbazoles [73]. Atroposelective cyclodehydration reaction. Atroposelective construction of axially chiral N-arylbenzimidazoles [78]. Proposed reaction mechanism for the atroposelective synthesis of axially chiral

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• -Michael addition of 2-tosylaminoenones with unsaturated pyrazolones using squaramide as catalyst. The reaction proceeded smoothly under mild conditions to afford the corresponding spiro[pyrazolone-tetrahydroquinolines] in high yields (up to 99%) with excellent diastereoselectivities (up to >25:1 dr) and

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• the keto group [11][12][13]. Consequently, our group developed an organocatalytic asymmetric Michael–acyl transfer reaction of α-nitroketones with unsaturated pyrazolones, 2-hydroxycinnamaldehydes, γ/δ-hydroxyenones, o-quinone methides, etc. [14][15][16][17][18]. Other groups also contributed

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• example, based on N-containing heterocycles (isoxazolones, pyrazolones, pyrazolidin-3,5-diones, and 1,2,3-triazolones [52]), sulfones [65], and phosphonates [54] (Scheme 8). Based on the data of EPR spectroscopy [35][38][49][50][66] and quantum chemical calculations [67], the maximum spin density in

• radical 20 and complex 49 results in the coupling product 48 (Scheme 18). The formation of radical 20 from the oxime 19 under the action of Cu(ClO4)2 in acetonitrile was proved by EPR spectroscopy [46]. Free-radical oxidative C–O coupling of pyrazolones 50 with different classes of N-hydroxy compounds

• optimization of the reaction conditions Fe(ClO4)3 was chosen as the optimal oxidant for the synthesis of C–O cross-dehydrogenative coupling products 51 (Scheme 19). The extremely persistent diacetyliminoxyl radical (20) [44] was directly introduced into the reaction with pyrazolones 50 with the formation of

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• of interest from a pharmacological point of view. The first and probably most frequently used method for the synthesis of pyrazolones is based on the Knorr condensation of β-ketoesters with substituted or unsubstituted hydrazines. However, these reactions often suffer from certain disadvantages, such

• hydroxy groups present in the heterocyclic ring in 6a. The 1H and 13C NMR spectroscopical analysis confirmed the structure of 8, which at the same time supported the formation of 6a in a yield of 84% during the previous reaction step. While N-unsubstituted pyrazolones such as 6a theoretically may have

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

• prepared. Moreover, the structure of a representative 5,5'-dioxo-4,4'-bipyrazole-4,4'-dicarboxylate was confirmed by X-ray crystal structure analysis. Keywords: dimerization; NMR (1H; 13C; 15N); pyrazolones; thionyl chloride; X-ray structure analysis; Introduction Many biologically active substances

• latter carbon atom. In contrast, only very few examples are described for pyrazolones with a C=O substructure attached to pyrazole C4. Thus, 3-methyl-1-phenyl-4-toluoyl-5-pyrazolone (= (5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)(4-methylphenyl)methanone) upon treatment with oxovanadium(V) compounds

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• has culminated in the development of a two-step, one-jar protocol for heterocycle formation and subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in moderate to excellent yields. Keywords: fluorination; heterocycles

• of base in the second step. In this report, we present a systematic approach to finding the optimal conditions, which are most compatible with both steps. Notably, fluorinated pyrazolones have the potential to be useful pharmaceutical or agrochemical products, given the desirable properties that can

• be obtained on introduction of fluorine to a molecule [18][19][20][21][22][23][24][25]. However, there have been limited reports on the synthesis of fluorinated pyrazoles, but fluorinated pyrazolones remain poorly studied [26][27][28][29][30]. Results and Discussion Initially the mechanochemical

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• pyrazolones The group of Krasavin prepared both pyrazole- as well as pyrazolone-containing peptidomimetics via a sequential hydrazino-Ugi/Paal–Knorr condensation [94]. In their first approach, pyrazoles were obtained in good yields, however, with a limited scope of the condensation substrates (Scheme 32

An easy direct arylation of 5-pyrazolones

• Hao Gong,
• Yiwen Yang,
• Zechao Wang and
• Chunxiang Kuang

Beilstein J. Org. Chem. 2013, 9, 2033–2039, doi:10.3762/bjoc.9.240

• Education, Shanghai 200092, China 10.3762/bjoc.9.240 Abstract A mild, efficient and catalytic ligand-free method for the direct arylation of 5-pyrazolones by Pd-catalyzed C–H bond activation is reported. The process smoothly proceeds and yields are moderate to excellent. Keywords: arylation; aryl halide

• ; C–H bond activation; Pd(OAc)2; pyrazolone; Introduction 5-Pyrazolones are attracting considerable research interest because of their unique chemical properties and their structures that facilitate their application as biological and pharmaceutical intermediates and products [1][2][3]. Over the

• years, many of the biological activities of pyrazolones such as their antipyretic, analgesic [4][5], anti-inflammatory [6][7], antitumor [8][9], antiviral, antibacterial [10], and herbicidal [11] properties have been discovered and investigated. Pyrazolones are also potent inhibitors of telomerase

Recent progress in the discovery of small molecules for the treatment of amyotrophic lateral sclerosis (ALS)

• Allison S. Limpert,
• Margrith E. Mattmann and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2013, 9, 717–732, doi:10.3762/bjoc.9.82

• , allowed the researchers to identify three distinct chemical series that were selected for optimization based on their ability to reduce both cellular toxicity and mutant SOD1 protein aggregation: arylsulfanyl pyrazolones (ASP, 10), cyclohexane-1,3-diones (CHD, 11), and pyrimidine 2,4,6-triones (PYT, 12

The tert- amino effect in heterocyclic chemistry: Synthesis of new fused pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives

• Dipak Prajapati and
• Kalyan Jyoti Borah

Beilstein J. Org. Chem. 2007, 3, No. 43, doi:10.1186/1860-5397-3-43

• progress to understand the exact mechanism of the reaction. Conclusion In conclusion, we have demonstrated that N-phenyl-3-substituted pyrazolones can be used for the intramolecular alpha-cyclisation of tertiary amines [33] for the synthesis of pyrazolinoquinolizine and 1,4-oxazinopyrazoline derivatives in