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

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

• amines with different nucleophilicity, namely benzylamine (primary alkylamine), morpholine (secondary alkylamine) and aniline (aromatic amine). We first examined the reaction of 1,2,4-oxadiazole-1,3-diketone 1a (σm/σp 0.463/0.575, which is quite close to the constants of the CO2Me group, so a successful

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

• 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

• quinuclidine to direct fluorination reactions of 1,3-diketone and 1,3-ketoester substrates using fluorine gas can give difluorinated products by a simple batch process, offering a potentially valuable route to the synthesis of difluoromethylene compounds that is suitable for inexpensive scale-up. Results 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

• 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

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

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

• ; 4, Figure 1) [36][37]. The relevance of acridine in drug discovery galvanized Singh and co-workers [38] to develop a water-promoted three-component reaction involving aldehydes 5, cyclic 1,3-diketone 6 and ammonium acetate powered by microwave irradiation resulting in 4-arylacridinediones 7 in

• -ones 24 using substituted phenylenediamine 23, aldehydes 5 and cyclic 1,3-diketone such as tetronic acid 6c under microwave irradiation in aqueous conditions delivering the product in good yields (70–89%). The use of a non-polar solvent resulted in the formation of side products like benzimidazole

• . The postulated mechanism indicates the formation of acylimine A from the lanthanum oxide-catalyzed reaction of aldehyde and 77. Further, addition of acyclic 1,3-diketone ester enolate to acylamine A form B which upon subsequent cyclization and dehydration resulted in the formation of desired products

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

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• as a mixture of regioisomers (6:1) (Table 2, entry 10). In addition, the possibility to perform the reaction of 2-azidophenyl phenyl selenide (1a) with β-keto-esters, β-keto-amides and α-cyano-ketones 2f–k was also investigated. The reaction conditions optimized for 1,3-diketone 2a were employed, but

Organofluorine chemistry: Difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring

• Mathew J. Jones,
• Ricardo Callejo,
• Alexandra M. Z. Slawin,
• Michael Bühl and
• David O'Hagan

Beilstein J. Org. Chem. 2016, 12, 2823–2827, doi:10.3762/bjoc.12.281

• compound was prepared by direct difluorination of the corresponding α,α-dimethylated 1,3-diketone with DAST. The presence of the two 1,3-diaxial fluorine atoms in structure 4c is responsible for the facial polarisation on the cyclohexane ring. We have demonstrated the intermolecular electrostatic

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• -membered heterocycle containing two adjacent nitrogen atoms. Pyrazole Pyrazole is a well-studied 5-membered heterocycle that has been traditionally synthesized either via the Knorr [151] (1,3-diketone and hydrazine) or von Pechmann [152] (olefin and diazomethane followed by oxidation) strategies. Figure 7

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• review, Lou and co-workers reported an additional example of conjugate addition–enantioselective protonation involving an α,β-unsaturated ketone. In the new report, a chiral primary amine catalyzed conjugate addition of a 1,3-diketone nucleophile into an in situ generated ortho-quinone methide was

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• couplings. Thus, a library of specifically substituted bipyridine derivatives was generated, showing the versatility of the simple 1,3-diketone-based approach to this important class of ligands. Keywords: 2,2-bipyridines; cross couplings; cyclocondensation; β-ketoenamides; nonaflates; Introduction In 2009

Recent advances in N-heterocyclic carbene (NHC)-catalysed benzoin reactions

• Rajeev S. Menon,
• Akkattu T. Biju and
• Vijay Nair

Beilstein J. Org. Chem. 2016, 12, 444–461, doi:10.3762/bjoc.12.47

• for the asymmetric synthesis of functionalised cyclopentanones was disclosed in 2009 by Rovis. The chiral secondary amine 60 catalyzes the initial asymmetric Michael addition of an 1,3-diketone and an enal to afford a δ-ketoaldehyde 61. Subsequently, a cross-benzoin reaction of the latter promoted by

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• -workers [71] successfully achieved the selective mono-α-chlorination of β-keto esters/amides and 1,3-diketone 78 by employing an electrochemical synthesis via a catalysis by means of Cu(OTf)2. The synthesis of chlorinated carbonyl products 79 were acquired in a divided cell using aqueous HCl as chlorine

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• carbon signals and an amide carbon signal appear at 190.6, 188.8, and 165.1 ppm, respectively. In addition, a methine carbon signal appears at 60.4 ppm. The structural confirmation of α-amido-1,3-diketone 3e by one- and two-dimensional NMR spectroscopic data is depicted (see Supporting Information File 1

• various substituted benzoic acids 2d–g as well and the resultant α-amido-1,3-diketones 3k–o are obtained in moderate to good yields (Figure 3). The mechanism for the formation of α-amido-1,3-diketone 3 is given in Scheme 2. Initially, by thermolysis, α-azidochalcone undergoes denitrogenative decomposition

• to form a cyclic imine – a highly strained three-membered 2H-azirine, 4. Subsequent attack by the acid results in the aziridine adduct 5, which then undergoes intramolecular nucleophilic addition on the carboxylic group with the nitrogen lone pair, ultimately yielding α-amido-1,3-diketone 3 by ring

(CF₃CO)₂O/CF₃SO₃H-mediated synthesis of 1,3-diketones from carboxylic acids and aromatic ketones

• JungKeun Kim,
• Elvira Shokova,
• Victor Tafeenko and
• Vladimir Kovalev

Beilstein J. Org. Chem. 2014, 10, 2270–2278, doi:10.3762/bjoc.10.236

• JungKeun Kim Elvira Shokova Victor Tafeenko Vladimir Kovalev Laboratory of Macrocyclic Receptors, Department of Chemistry, Moscow State University, Lenin’s Hills, Moscow 119991, Russia 10.3762/bjoc.10.236 Abstract A very simple and convenient reaction for 1,3-diketone preparation from carboxylic

• the most important class of organic compounds, since they are applied as key structural blocks in organic syntheses, exhibit different kinds of biological activities, and display a broad range of ionophoric properties [1][2][3]. The method most frequently used for 1,3-diketone synthesis is the Claisen

• (2а), which was initially formed as the result of an intramolecular cyclization of 1a, underwent a further acylation with the formation of 1,3-diketone 3a. In contrast, γ-phenylbutanoic acid (1c) was quantitatively transformed only to the tetralone 2с (Table 1, entries 10 and 11). The acid-catalyzed

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• use of 1,3-diketone, 1,3-ketoester and 1,3-diester derivatives in retrosynthetic planning is widespread in general organic chemistry and numerous terpenes, heterocycles and steroids originate from such simple yet synthetically versatile substrates [16][17][18][19]. In contrast, despite the

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• different binding ability toward water activation, we wondered whether the intermolecular O-addition could be achieved through ligand tuning. In this report, we focus on the cyclic 1,3-diketone nucleophiles due to A) the transformation is challenging and has never been reported in the past, B) vinyl ether

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• to the thiazolidinedione moiety as experienced using other reducing systems. As an aside the synthesis of 2-pyridones (i.e. 1.42) can be achieved via a number of methods. For example the classical Guareschi–Thorpe condensation in which cyanoacetamide reacts with a 1,3-diketone delivers highly

Tandem dinucleophilic cyclization of cyclohexane-1,3-diones with pyridinium salts

• Mostafa Kiamehr,
• Firouz Matloubi Moghaddam,
• Satenik Mkrtchyan,
• Volodymyr Semeniuchenko,
• Linda Supe,
• Alexander Villinger,
• Peter Langer and
• Viktor O. Iaroshenko

Beilstein J. Org. Chem. 2013, 9, 1119–1126, doi:10.3762/bjoc.9.124

• is quickly decomposed by silica gel liberating the desired product 3a or 6a, which was finally eluted from silica. The formation of a precipitate must be a driving force of the reaction promoted by DIPEA/KI (see Supporting Information File 2, thermodynamic analysis). The reaction starts with 1,3

• -diketone deprotonation and nucleophilic attack of potassium 3-oxocyclohex-1-enolate on pyridinium cation, which yields an intermediate with a new C–C bond, and this is a key stage in the reaction. The C–O bond formation can be excluded in the initial stage (see Supporting Information File 2 for the

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• cyclopentadienes, and followed by a hydrogenation reaction [30][31]. The synthesis of AZg (Ar = 3,5-dimethoxyphenyl, Ar’ = H) was performed from the corresponding 1,3-diketone 4 (Scheme 3b). 2,2-Dimethoxy-1,3-diarylpropane-1,3-dione 5g was prepared from 1,3-dione 4 (R = 3,5-dimethoxybenzene) according to the

Perhalogenated pyrimidine scaffolds. Reactions of 5-chloro- 2,4,6-trifluoropyrimidine with nitrogen centred nucleophiles

• Emma L. Parks,
• Graham Sandford,
• John A. Christopher and
• David D. Miller

Beilstein J. Org. Chem. 2008, 4, No. 22, doi:10.3762/bjoc.4.22

• , many pyrimidine derivatives have been used for various medicinal applications (Figure 1) [1][2][3]. Synthesis of pyrimidine rings most commonly involves cyclocondensation reactions of amidine, guanidine or thiourea derivatives with either 1,3-diketone or 1,3-diester systems [4][5]. However, many of

Multiple hydride reduction pathways in isoflavonoids

• Auli K. Salakka,
• Tuija H. Jokela and
• Kristiina Wähälä

Beilstein J. Org. Chem. 2006, 2, No. 16, doi:10.1186/1860-5397-2-16

• , DIBAH) occurs normally by 1,2-attack, this being a key step in the well known "carbonyl transposition" of 1,3-diketone enol ethers into enones (R3O-CR=CR1-COR2 → R-CO-CR1=CHR2). [11][12][13][14][15] Prior to our work there were no reports on the reduction of isoflavones containing free hydroxy groups