Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• interrupted Kröhnke reaction (Scheme 1B) [51][52]. The main step of this process is an intermolecular cyclization of the formed 1,5-diketone followed by aromatization. Previously we have shown that 1,3-diketones bearing an electron-withdrawing group (EWG) adjacent to one of the carbonyls readily react with in

• heterocycles are isoelectronic to an ester or a carbamoyl group, we were interested in testing various heterocycles as electron-withdrawing groups for activation of the carbonyl group in 1,3-diketones. In order to compare the electron-withdrawing ability of heterocycles and previously studied EWGs, we tried to

• was released [57] allowing direct comparison of different substituents. On the basis of the calculated Hammett constants, we have selected a model series of 1,3-diketones, bearing heterocyclic substituents with a range of electron-withdrawing ability (Figure 2). For the amine model series, we used

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

• hydrazines 3 (Scheme 1) [44]. It is important for a chemoselective synthesis that the 1,3-diketones 2 formed are not further acylated, which is prevented by using LiHMDS as a base. The method provides good to excellent yields and tolerates diverse functional groups. However, one limitation of the synthesis

• is that the reaction with methylhydrazine leads to two different regioisomers. Shen et al. used a concept developed by them for the C-acylation of β-ketoesters for the one-pot synthesis of pyrazoles. SmCl3-catalyzed acylation of these yields the 1,3-diketones 4, and after cyclization with hydrazine

• substrates also increase yields. The ionic liquid [bmim][InCl4] can be used as a catalyst for the one-pot synthesis of pyrazoles 68 from 1,3-diketones, aldehydes, and hydrazines (Scheme 23) [101]. The synergistic effect between anion and cation favors high regioselectivity, and high yields can be observed in

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• a substituent R5 located at carbon C-4 gave good yields, except for methoxy and benzyloxy which did not work at all. Dienes derived from 1,3-diketones (R6 = Me, Ph) gave similar yields to those obtained from dienes derived form β-ketoesters, although yields were slightly lower in case of R6 = Me

• %. Employment of dienes derived from 1,3-diketones (R3 = Me, Ph) proved to be unsuccessful, presumably due to the lower nucleophilicity of these dienes as compared to those derived from β-ketoesters (R3 = Oalkyl). Substituents located at carbon C-4 of the diene (R1) were generally tolerated as well. In fact

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• Swing Road, Greensboro, North Carolina, NC 27409, USA 10.3762/bjoc.20.41 Abstract Solutions of 1,3-diketones and 1,3-ketoester derivatives react with fluorine to give the corresponding 2,2-difluoro-1,3-dicarbonyl derivatives in the presence of quinuclidine. Quinuclidine reacts with fluorine in situ to

• agents offers an alternative fluorination route, for example, the reactions of MeCN solutions of 1,3-diketones with electrophilic fluorinating agents such as Selectfluor eventually give the corresponding 2,2-difluoro-1,3-diketone derivatives [12]. Monofluorination of the 1,3-diketone substrates is rapid

• corresponding 2,2-difluoroketones [15]. In related kinetic studies concerning the electrophilic 2-fluorination of 1,3-diketones with Selectfluor [16][17], we demonstrated that the rate-determining step for difluorination was enolization of the intermediate 2-fluoro-1,3-diketone. Monofluorination of 1,3

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• in combination with di-tert-butyl peroxide (DTBP) as an oxidant enables the CDC of the C(sp3)–H bond in the α-position to oxygen of various ethers with the active methylene C(sp3)–H bond in 1,3-diketones (Scheme 17) [78]. This method can generate various functionalized molecules and is expected to

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• trapping by adding MeLi (1.05 equiv), which indeed led to a significant increase in yield and selectivity due to the high reactivity of the lithium dialkyl zincate enolate. Various 1,3-diketones 39 were prepared using this method with good yields and excellent enantioselectivities while only the trans

A one-pot electrochemical synthesis of 2-aminothiazoles from active methylene ketones and thioureas mediated by NH₄I

• Shang-Feng Yang,
• Pei Li,
• Zi-Lin Fang,
• Sen Liang,
• Hong-Yu Tian,
• Bao-Guo Sun,
• Kun Xu and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2022, 18, 1249–1255, doi:10.3762/bjoc.18.130

• protocol proceeds in an undivided cell equipped with graphite plate electrodes under constant current conditions. Various active methylene ketones, including β-keto ester, β-keto amide, β-keto nitrile, β-keto sulfone and 1,3-diketones, can be converted to the corresponding 2-aminothiazoles. Mechanistically

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• 1,3-diketones [21], etc. Electrosynthesis is considered as a more sustainable approach to perform chemical reactions, and an interesting alternative to conventional synthetic methods both in laboratory and industry processes. In fact, the electron may be considered to be a clean reagent, which

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• 1,3-diketones, β-ketoesters, or β-ketoamides. We optimized the reaction conditions to control the selectivity of the production of isoxazoles and circumvent other competing reactions, such as O-imidoylation or hetero [3 + 2]-cycloaddition. The reaction happens fast in water and completes within 1–2

• needed to be synthesized independently [23]. While ruthenium(II) and palladium catalysts are useful, they are expensive and environmentally unfriendly. The dehalogenation of hydroximoyl chlorides in the presence of a strong base to generate nitrile oxides and a follow-up cycloaddition with 1,3-diketones

• , we herein report a method for the synthesis of 3,4,5-trisubstituted isoxazoles in water under mild basic conditions at room temperature via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides (Figure 1). No additional metal catalyst was used. Results and

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• versatile starting materials in organic synthesis [1][2]. Specifically, due to their keto–enol tautomerism and high reactivity, diketones are excellent precursors for different pharmaceuticals [3]. Cyclic 1,3-diketones have been widely exploited to access enantiomerically enriched scaffolds with increased

• to synthesise indoloquinolizidines [5]. Moreover, six-membered and five-membered cyclic 1,3-diketones have been investigated in reactions with acetates of nitroalkenes [6], cyanoacrylates and benzylidene malononitriles [7], ortho-hydroxy-benzhydryl alcohols [8], α,β-unsaturated pyrazolamides [9] and

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• regioisomeric 1,2-oxazole derivatives. Accordingly, the synthetic route starts from the condensation of 1,3-diketones with N,N-dimethylformamide dimethylacetal to form β-enamino ketoester. The latter undergoes a subsequent cycloaddition reaction with hydroxylamine to form regioisomerically substituted 1,2

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• . Notably, the reaction did not proceed in the dark or in the absence of the photosensitizer at 30 °C; further, the reaction generated the desired product in lower yield at 120 °C. The scope was broad and tolerated a wide array of 1,3-keto esters and 1,3-diketones, as well as both benzylic and aliphatic C

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• esters 29, such as 1,3-diketones, β-ketoesters, cyclic 1,3-diketone (dimedone), and β-ketoamide, respectively, to afford desired 1,4,5-trisubstituted 1,2,3-triazoles containing glycosyl with high yield. It should be pointed out that no byproducts were recognized under optimized reaction conditions. In

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• -fused tetrahydrodibenzoacridinones 9 using phenanthren-9-amine 8, aldehydes 5, and cyclic 1,3-diketones 6 as structural units in ethanol under microwave irradiation to result in the targeted products in excellent yields. A conventional heating used for the same protocol delivered the desired products in

• synthesis of 3-functionalized indoles 34 by employing amines 32, arylglyoxal monohydrate 33 and cyclic 1,3-diketones 6 under microwave irradiation in the greener solvent system EtOH/H2O (Scheme 10). A plausible mechanism (Scheme 11) suggests a TFA-catalyzed Knoevenagel condensation between 4-hydroxy-6

• ). The synthesis of indoline-spiro fused pyran derivatives 53 was reported by Jiang and co-workers [57] employing a multicomponent reaction between substituted isatins 35, cyclic 1,3-diketones 6 and malononitrile (51) in an aqueous medium without any catalyst. Reaction diversity was examined by using

Synthesis of β-triazolylenones via metal-free desulfonylative alkylation of N-tosyl-1,2,3-triazoles

• Soumyaranjan Pati,
• Renata G. Almeida,
• Eufrânio N. da Silva Júnior and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2021, 17, 762–770, doi:10.3762/bjoc.17.66

• with cyclic 1,3-diketones to form various β-triazolylenones. Although the scope of the 1,3-dicarbonyl compound is limited, the protocol is very convenient and useful as it employs very mild reaction conditions. It is also highly regioselective and `affords only N1-alkylated products in moderate to

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• compounds 161 in high yield (Scheme 40, top). The reaction of CF3-substituted 1,3-diketones 165a–d in TfOH was also deeply investigated by Klumpp et al. [101]. The syn-indanes 166a–d could cleanly be generated after successive well-defined arylation reactions via 167 (Scheme 40, bottom). Moreover, the CF3

Annulation of a 1,3-dithiole ring to a sterically hindered o-quinone core. Novel ditopic redox-active ligands

• Sergey V. Norkov,
• Anton V. Cherkasov,
• Andrey S. Shavyrin,
• Maxim V. Arsenyev,
• Viacheslav A. Kuropatov and
• Vladimir K. Cherkasov

Beilstein J. Org. Chem. 2021, 17, 273–282, doi:10.3762/bjoc.17.26

• -methide moiety, compound 6c should exhibit a more complicated redox behavior compared to parent o-quinone. Despite 1,3-diketones presumably exist as enol tautomers [30], they are also often used as active methylene compounds. The introduction of a 1,3-diketone fragment at the backbone of the o-quinone

•  2. The high extent of enolization of 1,3-diketones results in lower nucleophilicity of the active methylene function. This fact enhances the reversibility of the dithiocarboxylation of sodium acetylacetonate. It is known that dithiocarboxylates and gem-dithiolates can lose CS2 resulting in active

• -wave band corresponds to the π–π* transition [50]. UV–vis spectra of 6b–d are more complicated and show the bands characteristic of both o-quinone and an attached fragment. So that o-quinone 6c displays absorptions typical of 1,3-diketones [51]. o-Quinone 6b exhibits intensive absorption peaks in the

Facile preparation and conversion of 4,4,4-trifluorobut-2-yn-1-ones to aromatic and heteroaromatic compounds

• Takashi Yamazaki,
• Yoh Nakajima,
• Minato Iida and
• Tomoko Kawasaki-Takasuka

Beilstein J. Org. Chem. 2021, 17, 132–138, doi:10.3762/bjoc.17.14

• structurally similar compounds [29] on the basis of 1) comparison of the chemical shift of the CF3 group and 2) the absence of a coupling between the vinylic and allylic protons. In order to explore other nucleophiles, we employed 1,3-diketones, such as 5-methylhexane-1,3-dione and 5,5-dimethylhexane-1,3-dione

Synthesis of new fluorescent molecules having an aggregation-induced emission property derived from 4-fluoroisoxazoles

• Kazuyuki Sato,
• Akira Kawasaki,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2020, 16, 1411–1417, doi:10.3762/bjoc.16.117

• ]. In addition, we reported that the reaction proceeded smoothly by starting with 1,3-diketones (1) to give 3 in excellent yields in a one-pot reaction. As part of a wider research program aimed at the applications of fluorinated 5-membered heteroaromatic systems, in this paper, we report the

• ][38], their optical properties feature a large Stokes shift and high molar absorption coefficients (ε) that are similar to the corresponding boron diketonates. The synthesis and properties of BKIs have been reported recently and they are easily accessible either from the corresponding 1,3-diketones 1

• or from isoxazoles 2 through a ring-opening reaction (Scheme 3). Based on the above observations, we attempted to introduce a fluorine atom into BKIs to access the corresponding α-fluorinated boron ketoiminates (F-BKIs, 9). First, we started from 1,3-diketones 1 and reacted them with ammonium formate

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

• . 1,3-Diketones and 1,3-ketoesters 45 undergo cross-dehydrogenative C–O coupling with oximes under the action of oxidizing agents [46], such as KMnO4, Mn(OAc)3 or the KMnO4/Mn(OAc)3 system (Scheme 15). A radical mechanism is suggested for the formation of the C–O coupling products 46 in which the

• oxidizing agent serves to generate oxime radicals from oximes and perform one-electron oxidation of 1,3-dicarbonyl compounds 45. The formation of oxime radicals under the reaction conditions was confirmed by EPR spectroscopy [46]. 1,3-Diketones and 1,3-ketoesters with easily oxidizable groups, such as allyl

• (products 46a,b, 46m,n), 1,3-diketones (product 46r), as well as lactones (products 46o–q) were used in the oxidative C–O coupling reaction. The coupling of oximes with 1,3-diketones proceeded in lower yields than with 1,3-ketoesters (products 46a and 46r). Despite the presence of t-BuOOH in the system, a

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• amount of HPW on silica decreased the yield of reaction [62]. The silica sulfuric acid (SSA) catalyst was synthesized by the treatment of silica gel with sulfuryl chloride under room temperature stirring. The catalyst was used in the acylation of amines with 1,3-diketones via C–C bond cleavage. Various

• protected aniline derivatives were obtained by the solvent-free reaction of anilines with 1,3-diketones at 120 °C or 140 °C in the presence of 2 equiv of water under 1 atm O2 atmosphere (Scheme 16). The probable reaction pathway for this reaction is shown in Scheme 16. Arylamine 15 attacks the activated

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• thiophenes (8aa–ai) were obtained in moderate to excellent yields (47–92%). When different 1,3-diketones were applied, the yields were affected by the keto–enol tautomer ratio. Alkyl substituents (isopropyl and cyclopropyl), which promote the enol forms of the ketones, afforded thiophenes 8aj and 8ak in good

Nucleophilic dearomatization of 4-aza-6-nitrobenzofuroxan by CH acids in the synthesis of pharmacology-oriented compounds

• Alexey M. Starosotnikov,
• Dmitry V. Shkaev,
• Maxim A. Bastrakov,
• Ivan V. Fedyanin,
• Svyatoslav A. Shevelev and
• Igor L. Dalinger

Beilstein J. Org. Chem. 2017, 13, 2854–2861, doi:10.3762/bjoc.13.277

• starting material and resinification. Apparently, it was caused by interaction of Et3N with ANBF because the blank experiment (1 + Et3N with no ketone added) also resulted in decomposition of ANBF. Therefore we studied reactions of 1 with more acidic 1,3-diketones, ketoesters and related compounds. The

• similar linear 1,3-diketones (Table 1, entries 1, 2 and 9). Another class of CH acids was studies in reactions with ANBF. In particular, 2,4-dinitrotoluene in the presence of Et3N was found to be unreactive, while 2,4,6-trinitrotoluene (TNT) gave the expected 1,4-adduct 15 in 74% yield (Scheme 6). Due to

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• [1,5-b]pyridazines along route B, 1-aminoimidazoles with no substituents at the C-5 atom of the original heterocycle and 1,3-dielectrophilic reagents are used, e.g., 1,3-diketones [24][25][26], β-ketoesters [24], α,β-unsaturated ketones [27][28], including those obtained in situ [29][30] or containing