Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• Interaction of 1,3-diketone 1 with formaldehyde First, we investigated the ability of formaldehyde to interact with 1,3-diketone 1 using the diffusion mixing technique. For this purpose, we carried out a series of reactions in a very simple device consisting of a large vial with formalin, inside which we

• %, respectively, when carrying out the reaction in chloroform or methanol over two days (Table 1, entries 3 and 7). In turn, in a system of two vials with diameters of 3.7 and 7.5 cm, and with a loading of diketone 1 that was five times greater, more than two thirds of the starting compound reacted within 24 h

• (Table 1, entries 11 and 13). Apparently, an increase in the surface area of the reaction solution promoted more efficient absorption of CH2O molecules, which accelerated the condensation reaction. The reaction of formaldehyde and diketone 1 in chloroform and acetonitrile predominantly led to diketo

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• anodic oxidation of chloride ions, thus replacing stoichiometric chemical oxidants. This catalytic electrochemical chlorination method is suitable for β-ketoesters 68 with electron-withdrawing or electron-donating groups on aryl substituents, as well as for β-diketone, and β-ketoamides. In 2020, Fang

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• compounds tend to deprotonate to form highly stable anions. The air stability of TBF conforms to that model. In contrast, although the dianion of BFC can be generated with tert-butoxide under inert atmosphere, in the presence of water it quenches and exposed to oxygen it oxidizes to form the diketone

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• ketones reacted well too. Accordingly, 3j was obtained in 42% yield. Enone 1k gave 3k in 51% yield, and after isolation by column chromatography the product was obtained in 13% yield. Difluoromethyl enol ether 3l was formed from diketone 1l in 25% yield. Finally, conversions of the two cyclic ketones 1m

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

• ) demonstrates the synthetic utility of the developed method. Keywords: aniline; benzannulation; condensation; 1,3-diketone; Hammett constants; terphenyl; Introduction The aniline moiety is omnipresent in the synthetic chemistry with applications ranging from building blocks to catalysis [1][2][3][4]. Among

• 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

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

• approach was also used to synthesize pyrazoles since the intermediary-formed diketone 18 forms the corresponding pyrazoles 17 in a Knorr reaction with 2-hydrazinyl-4-phenylthiazoles 15 in a one-pot process (Scheme 4) [52]. Piperidine was used as a catalyst for the Knoevenagel condensation. Remarkably

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• aromatic hydrocarbons; Introduction Quinones and their derivatives are applied in various fields such as chemical, environmental, and pharmaceutical industries [1][2][3][4]. Their cyclic diketone structures can easily transform into intramolecular unsaturated structures, and their distinct physical

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

• substituents, respectively, were also attempted but without success. In these cases, the sterically congesting ortho isopropyl and tert-butyl groups stymie the Friedel–Crafts acylation step leading to diketone (Scheme 1). Experimental and computational studies of 1,3-diarylisoacenofurans Purified

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• high reactivity of intermediate 7a (Scheme 4). After optimizing the successful synthesis of alkoxylated and diketone derivatives of 7a, we were intrigued to investigate whether other dicyanopyrazinoquinoxaline derivatives could undergo a similar transformation. To assess the efficacy of the reaction

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• ), deprotection, decarboxylation, oxidation, nitrogen extrusion (to cyclobutadiene) and Diels–Alder reaction yielded annulated tricycle 164. Further intramolecular [2 + 2] cycloaddition formed cubane precursor 165. From diketone 165, 1,3-cubane 166 was obtained by Favorskii ring contraction followed by

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

• 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

• , but the second fluorination step occurs only after reaction for several days. In the solid phase, mechanical milling of the diketone substrate with solid Selectfluor in the presence of sodium carbonate [13][14], and reaction of ketones with a strong base and an N–F reagent give rise to the

• 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

• bidimensional structures such as starphenes [34] from custom-made stable and soluble precursors. Interestingly, extrusion of CO from mono- or α-diketone precursors has also been achieved on metallic surfaces under ultra-high vacuum (UHV) conditions upon thermal annealing, photoirradiation or activation by the

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• alkyne group, in low yield (39%), with the majority of the starting alkyne being recovered (46%) (see Table S2, Supporting Information File 1). Increasing the amount of electrogenerated BF3 by applying 4 F/mol and extending the reaction time (5 h) reversed the selectivity in favour of the diketone 2jj

Synthesis of tetrahydrofuro[3,2-c]pyridines via Pictet–Spengler reaction

• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2023, 19, 991–997, doi:10.3762/bjoc.19.74

• of some of the products was investigated and selected synthetic transformations of the obtained tetrahydrofuro[3,2-c]pyridines were shown. Keywords: acid hydrolysis; 1,4-diketone; tetrahydrofuro[3,2-c]pyridines; Paal–Knorr reaction; Pictet–Spengler reaction; Introduction Hydrogenated furo[3,2-c

• hydrolysis of 4a was observed in most cases in trace amounts; an exception is entry 18 (Table 1), in which the 1,4-diketone 5a was isolated in 10% yield. With the optimized reaction conditions in hand, we investigated the scope of the developed tetrahydrofuro[3,2-c]pyridine synthesis. We found that a wide

• optimized reaction conditions, in addition to the desired tetrahydrofuro[3,2-c]pyridine (4h), led to the major formation of the corresponding 1,4-diketone 5h. This unexpected formation of 3-(2-oxopropyl)piperidin-4-one (5h) led us to the idea that the tandem sequence Pictet–Spengler cyclization/furan acid

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

• was not given for the different coupling constants between diester 1a and diketone 1b’. In the 13C NMR spectrum of diester 1a, two separate signals of carbonyl groups were observed at 163.2 and 163.3 ppm, indicating that the two ester functionalities were not equivalent. Moreover, the spectrum of

• acyl group are unknown, except for a derivative of cyclic diketone [20][21]. Although diacetyl derivative 13 has been reported in some studies [12][13][19], we corrected its structure to dihydrofuran 8. This is the first report of the synthesis of acylated nitrocyclopropanes 1. After the conjugate

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

• -1,2-diketone [21][22][23][24][25]. However, the direction of the transformation in each case depends on the structure of the bridge fragment. Thus, for example, the 1,3,5-hexatriene cyclization does not occur for pyrazole 1 and imidazole 2 derivatives, and the obtained products are formed exclusively

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• cyclization based on a bridgehead tertiary carbocation intermediate forging the B ring; iii) redox manipulations and a 1,2-migration as final steps. The synthesis started from (S)-ketone 44 which was prepared via asymmetric CBS reduction of diketone 26 (Scheme 7). Firstly, this (S)-ketone 44 was transformed

• -membered triflate 71 was synthesized from diketone 26 in 5 steps and 37% overall yield. Both fragments were assembled by a Sonogashira cross-coupling, affording 72 in 72% yield. In a first attempt, TBS protection was considered on the bicylo[3.2.1]octane. However, later in the strategy, the deprotection

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• , including two all-carbon quaternary centers, together with the non-enolizable cyclic α-diketone moiety collectively render aberrarone as an attractive but challenging synthetic target. Its congener elisabanolide (2) with a lactone in the D ring shows their potential biosynthetic relationship [2]. These

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

• tetraketones 11 promoted by base (Scheme 2) [25]. The equivalent reaction has not been reported for dihydrolevoglucosenone (Cyrene™) 12, and it was thought that the chiral 1,5-diketone products could be used to construct catalysts or ligands. The aldol/Michael cascade using conditions for the aldol reaction

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

• -diketone is captured by intramolecular reaction with an active substituent in the side chain (Scheme 1B) [24][25]. Thus, the combination of ESIPT-induced photoreactions of 3-hydroxypyran-4-one derivatives and various trapping methods opens up significant synthetic possibilities. At the same time, such

• -induced contraction of the pyranone ring will proceed under UV irradiation. At first, pyrazole 12a was selected as a model object for the investigation of this hypothesis. It was shown that the photoreaction of pyrazole 12a regiospecifically led to the formation of α-hydroxy-1,2-diketone 14a (Scheme 3

• pyranone ring proceeds under UV irradiation of compound 12a, while the 6π-electrocyclization products were not detected in the reaction mixture. However, it should be mentioned that the resulting α-hydroxy-1,2-diketone 14a has a relatively low stability and storing of the NMR sample of compound 14a in

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

• the nucleophilic addition and successive cyclization to happen. In addition, we further explored the scope of substrates with a trifluoromethyl group, a strong electron-withdrawing substituent, instead of methyl, an electron-donating group, in the 1,3-diketone starting materials (Table 2). The

• enol tautomer of the 1,3-diketone was predominant in CDCl3, while the keto tautomer was predominant in methanol-d4, which is a more polar solvent than CDCl3 (Figure 7). Our observations thus reinforce Meyer’s rule [34][35], which states that the keto tautomer is favored as the solvent polarity

• chloroform or dichloromethane (Table 1, entries 9 and 10). A plausible mechanism for the formation of the 3,4,5-trisubstituted isoxazoles 3a (the only regioisomer that was formed) is shown in Figure 8. In a polar solvent like water or methanol, the 1,3-diketone is deprotonated by the base DIPEA to form the

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• reactive oxygen species (ROS) generation, resulted from the interactions between nucleophilic biomolecules and 1,4-naphthoquinonic nucleus of menadione and its derivatives. The presence of an α,β-unsaturated diketone in the quinone structures allows them to accept electrons through reduction processes

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

• (Scheme 1, 3e). These experiments revealed that the best results were achieved in chloroform at room temperature with catalyst D, using 1 equiv of diketone and 2 equiv of N-Boc-substituted oxindole 2a. Under optimised conditions, the substrate scope of the reaction was examined by using various

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

• -oxazoles are: the 1,3-dipolar cycloaddition of alkenes and alkynes with nitrile oxides, and the reaction of a three-carbon atom component, such as a α,β-unsaturated ketone or a 1,3-diketone with hydroxylamine hydrochloride [33]. Recently, Rosa et al. reported a useful procedure for the synthesis of various

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• proceeded with full retainment of the labelling in both cases (Scheme 1B). Subsequent chemical degradation through acid catalysed conversion into 5, oxidative cleavage to the diketone 13, BF3∙OEt2 mediated ring closure by aldol reaction and catalytic hydrogenation gave 14. For both experiments a full