Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• the literature, we found that 1,5-diketones and 1,5-ketoaldehydes have been utilized in retro-Michael reactions catalyzed by NaOH or KOH at extremely high reaction temperatures [26]. Some examples are also described under milder conditions, where the starting compounds are obtained with good chemical

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

• indoles 96 or pyrroles 99 and 1,4 diketones 97, respectively, the authors were able to achieve very good to near-perfect yields with consistently high enantioselectivities. Configurational stabilities of the products 98 and 100 were explored in toluene at 110 °C. Rotational barriers were calculated to be

• -catalyst containing transition metals but are purely of organocatalytic nature. In these experiments, the chiral phosphoric acid C28 catalyzed the reaction of aminopyrroles 101 and 1,4-diketones 102. Under the optimized reaction conditions, the yields were good to excellent, and high levels of

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• compounds (β-diketones, β-ketoesters, and malonic esters) with TBHP via homogeneous and heterogeneous Cu(II)-catalysis were developed (Scheme 10) [45][46][47]. It was assumed that the reaction pathway includes the formation of diketonate complex A from β-dicarbonyl compound 19 and copper(II) salt, which

• -unsaturated esters 143 and TBHP to afford α-peroxy-γ-diketones 145 was also disclosed under the catalysis of dirhodium(II) complex Rh2(esp)2 (esp = α,α,α′,α′-tetramethyl-1,3-benzenedipropanoate) (Scheme 45c) [109]. A three-component radical coupling reaction has been established for the assembly of β

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

• -diketones has been developed. The electron-withdrawing power of the heterocyclic substituent (which can be estimated on the basis of calculated Hammett constants) in the 1,3-diketone plays a pivotal role in the studied reaction. The series of meta-hetarylanilines prepared (21–85% isolated yield

• 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

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• original Biginelli reaction shown in Scheme 1A was significantly extended by variation of the 1,3-dicarbonyl-containing building blocks. Many groups have elegantly demonstrated the synthetic versatility of numerous enolizable carbonyl components, including β-keto esters, cyclic/acyclic β-diketones, β-keto

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

• acetylacetonate 20. Extension of the sequence by cyclization with hydrazine leads to the pyrazole products 21 (Scheme 5) [53]. The method works best with acetylacetonates, since deprotonation of other diketones with NaOEt leads to deactivation of the isothiocyanates. A limitation of the method is the formation of

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• treatment of Alzheimer's disease [3][4]. Likewise, RL91 and BHMPC are active for selective cell growth inhibition of the resistant lines (Figure 1) [5][6]. Their synthesis mainly involves a cascade Michael–aldol reaction between enones and suitable Michael donors such as β-ketosulfones, β-diketones, or

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

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• congestion to the highly reactive 1,3-carbons on the furan ring. Thus, phthaloyl chloride was reacted with mesitylene or 1,3,5-triethylbenzene to produce the corresponding diketones 21 and 22. Each diketone was in turn reacted with zinc metal in glacial acetic acid [9] to afford the corresponding 1,3

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

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• π-CPCs relies on the extrusion of carbon monoxide (CO) from soluble precursors incorporating bridging ketone fragment(s). In contrast with the thermal activation required in retro-Diels–Alder reactions, photoirradiation of α-diketones triggers a Strating–Zwanenburg decarbonylation leading to the

• release of two CO molecules (Scheme 1, top right). After a proof of concept on pentacene with soluble precursors including a bicyclo[2.2.2]octane-2,3-dione framework [20][21], α-diketones were intensely exploited as soluble photoprecursors for the synthesis of acenes of increasing length up to undecacene

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

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• trifluoroacetonitrile imine, are highly versatile in that they react with olefins, acetylenes, dimethyl fumarate, dimethyl maleate, β-diketones, β-keto esters, bicyclic olefins, and potassium isothiocyanate and isocyanate affording the corresponding trifluoromethyl-containing compounds, generally with good yields [51

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

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• 3b used in only three cases [12][13][19], to the best of our knowledge. Extending beyond Scheme 2, only two syntheses of nitrocyclopropanes containing cyclic keto esters or diketones have been reported [20][21]. These findings indicate that the synthesis of nitrocyclopropanes with an acyl group is

• quite difficult, although they would be very useful in synthetic chemistry, if available. In this study, we investigated the synthesis of nitrocyclopropanes using keto esters 3c–f and diketones 3b and 3g instead of diester 3a as the starting 1,3-dicarbonyl compounds. Results and Discussion We commenced

• detected (Scheme 3). Next, method a (Scheme 2) was employed to synthesize nitrocyclopropanes 1 possessing an acyl group. Keto esters 3c–f and diketones 3b and 3g underwent conjugate addition to nitrostyrene 2a to afford the corresponding adducts 4b–g with moderate yields (Table 1). For unsymmetrical

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• pyranone ring leading to the formation of α-hydroxy-1,2-diketones. This phototransformation is initiated by an excited state intramolecular proton transfer (ESIPT) process. In most cases the resulting α-hydroxy-1,2-diketones are unstable and their further reactions open access to various original products

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

Oxa-Michael-initiated cascade reactions of levoglucosenone

• Julian Klepp,
• Thomas Bousfield,
• Hugh Cummins,
• Sarah V. A.-M. Legendre,
• Jason E. Camp and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2022, 18, 1457–1462, doi:10.3762/bjoc.18.151

• from 12 gave moderate to low yields of bridged species, most effectively with electron-poor aromatic aldehydes, and reactions had to be monitored to optimize conversions and prevent decomposition (Scheme 2) [14]. Analysis of the NMR spectra indicated that instead of the open chain diketones 13, the

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

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• 1,3-dicarbonyl compounds using a catalytic amount of hydrazine hydrate without solvent in a short reaction time (10 min) [14]. Reactions of 2-aminothiophenols with β-keto esters and β-diketones under microwave irradiation (MWI) using basic alumina as heterogeneous catalyst without solvent afforded 4H

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

On Reuben G. Jones synthesis of 2-hydroxypyrazines

• Pierre Legrand and
• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 935–943, doi:10.3762/bjoc.18.93

• was simplified later on by the use of the hydrochloride salts of the α-aminoamides 2, instead of their free base, along with the addition of a second equivalent of sodium hydroxide [13]. As expected, from asymmetric 1,2-diketones (1, R1 ≠ R2 and ≠ H), reports [14][15][16] describe the occurrence of

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• contraction of the 4-pyranone cycle 1 leading to the formation of unstable α-hydroxy-1,2-diketones. These intermediates can be captured intramolecularly using various functional groups present in the molecule or by employment of additional reagents. For example, a convenient method for trapping of unstable α

• -hydroxy-1,2-diketones 2 is the condensation with 1,2-phenylenediamine resulting in the formation of fused quinoxalines 3 (Scheme 1A) [22]. Another variant of similar catching reaction is reduction by NaBH3CN with the formation of diols 4 (Scheme 1A) [23]. Thus, the introduction of additional reagents

• allows the use of photogenerated α-hydroxy-1,2-diketones in the synthesis of various products. An alternative approach for trapping of such unstable intermediates is the preliminary introduction of functional groups into the 3-hydroxypyran-4-one structure. In this case, the intermediate α-hydroxy-1,2

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

• presence of a multifunctional squaramide catalyst. Michael adducts were obtained in high enantioselectivities and in moderate diastereoselectivities. Keywords: cyclopentane-1,2-dione; enantioselective catalysis; Michael addition; organocatalysis; squaramide; Introduction Diketones are generally very

• 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