Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• natural products of microbial origin such as HHQ and its C5-congener. Two compounds with high activity against S. aureus have been identified among the newly obtained quinolones, with MICs ≤ 3.12 and ≤ 6.25 µg/mL, respectively. Keywords: antibacterial; β-keto amides; enaminones; 4-quinolones; quorum

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

• derivatives 11 were obtained along with the expected polyaromatic compounds 12 (Scheme 1D). Results and Discussion The starting terarylenes 9 were obtained based on the reaction of the corresponding enaminones 13 with cyanamide (14). It should be noted that a similar approach is described in the literature

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• activation/annulation cascade of readily available enaminones with iodonium ylides towards the convenient synthesis of isocoumarins. This coupling system proceeds in useful chemical yields (up to 93%) via a cascade C–H activation, Rh-carbenoid migratory insertion and acid-promoted intramolecular annulation

• achievements, established methods often require the use of stoichiometric oxidants or harsh conditions, thus limiting their broad applicability. Consequently, it is still highly desirable to exploit innovative and convenient methods for the rapid construction of isocoumarins. Enaminones are bench stable and

• easily available, which have been established as versatile synthetic building blocks for the synthesis of cyclic scaffolds [25]. In 2016, Zhu et al. reported the first example of a Rh-catalyzed C–H functionalization of enaminones with alkynes and α-diazo-β-ketoesters to access naphthalenes [26]. Very

An isoxazole strategy for the synthesis of 4-oxo-1,4-dihydropyridine-3-carboxylates

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2022, 18, 738–745, doi:10.3762/bjoc.18.74

• , resulted from the deacylation of intermediate 3g, was isolated in the reaction carried out at 70 °C. This side process is probably the reason for the decrease in the yield of the target pyridone 2g. Considering that isoxazoles were previously reduced to enaminones by other reducing systems [24][25][26][27

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• reported Lewis acid-mediated enone reactions with alkyl azides yielding enaminones [48]. Similarly, as with ketone, reactivity of the enone derivative 4 with HN3 in the presence of BF3⋅OEt2 (Table 2, entry 1) was examined. It was shown that a longer time is needed to achieve conversion, and the yield was

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• , Stellenbosch University, Matieland 7602, Stellenbosch, South Africa 10.3762/bjoc.17.170 Abstract A wide range of N-(ethoxycarbonylmethyl)enaminones, prepared by the Eschenmoser sulfide contraction between N-(ethoxycarbonylmethyl)pyrrolidine-2-thione and various bromomethyl aryl and heteroaryl ketones

• temperature and microwave power, although requiring much longer time. A possible mechanism for the cyclization is presented, and further functionalization of the newly created pyrrole ring in the dihydropyrrolizine core is described. Keywords: dihydropyrrolizines; enaminones; microwaves; silica gel

• ] and procuramine (10) [13], have also attracted attention recently. Our continuing efforts to exploit enaminones as building blocks for the synthesis of alkaloids and other nitrogen-containing heterocycles have largely concentrated on targets containing indolizidine and quinolizidine backbones [14

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

• subsequent elimination of HBr leads to the triazole ring [39]. Another metal-free strategy to 1,4,5-trisubstituted 1,2,3-triazoles 8 was realized by regioselective reaction of aryl azides 7 with enaminones 6 in the presence of triethylamine, water, and ionic liquid (IL). This method exhibits good functional

• group compatibility, including using enaminones containing aliphatic and aromatic substituents as well as azide compounds containing electron-donating and -withdrawing groups on the aromatic ring. In all cases, only 4-acyl-substituted regioisomers were obtained (Scheme 4) [40]. The mechanism was also

• enaminones 18 with tosyl azide. A wide range of desired 5-thiolated 1,2,3-triazoles 19 has been prepared in good to high yield in H2O as solvent using TMEDA as a weak base, thus providing an environmentally friendly procedure that was demonstrated to be practicable also on a gram scale. A wide range of β

Synthesis of 1-indolyl-3,5,8-substituted γ-carbolines: one-pot solvent-free protocol and biological evaluation

• Premansh Dudhe,
• Mena Asha Krishnan,
• Kratika Yadav,
• Diptendu Roy,
• Krishnan Venkatasubbaiah,
• Biswarup Pathak and
• Venkatesh Chelvam

Beilstein J. Org. Chem. 2021, 17, 1453–1463, doi:10.3762/bjoc.17.101

• alkaloid ingenine B [20]. The iodine-catalyzed [3 + 3] cycloaddition of indolyl alcohol to enaminones [21] and the thiourea-catalyzed iso-Pictet–Spengler reaction of isotryptamine with aldehydes [22], are some noteworthy contributions to the field. A cascade or domino reaction is an interesting approach

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• Ekaterina E. Stepanova Maksim V. Dmitriev Andrey N. Maslivets Department of Chemistry, Perm State University, ul. Bukireva 15, Perm 614990, Russian Federation 10.3762/bjoc.16.193 Abstract Two synthetic approaches to enaminones fused to 1,4-benzothiazin-2-one moiety, which can be interesting in

• studies on biological activity, chemosensors, and fluorescence, were developed via the reaction of furan-2,3-diones or acylpyruvic acids in the presence of carbodiimides with o-aminothiophenols. The target enaminones were formed together with pharmaceutically interesting 2-hydroxy-2H-1,4-benzothiazin-3(4H

• ; 1,4-benzothiazine; cyclocondensation; diversity-oriented synthesis; furan-2,3-dione; Introduction Enaminones fused to the 1,4-benzoxazine-2-one I or quinoxaline-2(1H)-one II moiety (Figure 1) represent an intensively investigated class of enamines. Undying interest in these compounds is due to the

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• ][38][39] or triketones [10][13] and enaminones [40][41][42][43] as starting materials. For the synthesis of cinnoline derivatives, aryldiazenes and aryltriazenes are substrates of choice for transition-metal-catalyzed (Rh, Pd, Cu) cross-coupling reactions, followed by intramolecular cyclizations [44

One-pot synthesis of substituted pyrrolo[3,4-b]pyridine-4,5-diones based on the reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamide with amines

• Valeriya G. Melekhina,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Vitaly S. Mityanov,
• Artem N. Fakhrutdinov,
• Arkady A. Dudinov,
• Vasily A. Migulin,
• Yulia V. Nelyubina,
• Elizaveta K. Melnikova and
• Michail M. Krayushkin

Beilstein J. Org. Chem. 2019, 15, 2840–2846, doi:10.3762/bjoc.15.277

• material. Thus, optimal conditions could be established for this reaction, allowing the synthesis of enaminones 7 in moderate yields (Table 2). Note, that this is the first time for such a transformation to be reported. There are two possible reaction pathways for the investigated conversion. The first

• procedure due to circumventing the isolation of the intermediate enaminones 7. Applying this method to the whole range of substrates 2 and 3 allowed to access the target materials 1 in high yields (Table 4). Again, the transformation of 7 to 1 may have proceeded via one of two possible routes: The two-step

• substituted pyrrolopyridinones 1 was developed. The reaction of N-(1-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-2-oxo-2-arylethyl)acetamides with a diverse family of amines was performed in two consecutive steps, without isolation of the intermediate enaminones 7. The described one-pot method combines

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• enaminones 61 by conjugative addition of heteroarylamines 3 with α,β-ynones 60 (Scheme 20). Optimization of the reaction inferred that CuI with dimethylformamide (DMF) at 100 °C under air would be the best conditions for a maximum yield. The reaction viability was also tested without the isolation of product

Synthesis of functionalised β-keto amides by aminoacylation/domino fragmentation of β-enamino amides

• Pavel Yanev and
• Plamen Angelov

Beilstein J. Org. Chem. 2018, 14, 2602–2606, doi:10.3762/bjoc.14.238

• -protected amino acids. Domino fragmentation of the obtained intermediates leads to functionalised β-keto amides, bearing a protected amino group in their side chain. Keywords: amino acids; C-acylation; domino reaction; enamines; enaminones; keto amides; retro-Mannich; Introduction The acylation of amide

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• , authentically mild conditions (40 °C stirring) as well as practical scalability. Keywords: additive-free; catalyst-free; cycloaddition; enaminones; on water; 1,2,3-triazole; Introduction Discovering sustainable chemical syntheses constitutes one central issue of modern organic chemistry. A large number of

• construction, enamines with good stability and easy availability such as enaminones have exhibited also conspicuously versatile application in the metal-free synthesis of divergent 1,2,3-triazoles by directly acting as starting materials [51][52][53][54]. In 2016, Dehaen and co-workers [55] reported the

• lower yield than the equivalent reaction using water (entry 11, Table 1). To examine the scope of this water-mediated 1,2,3-triazole synthesis, a broad range of enaminones 1 was then employed to react with tosyl azide under the optimal conditions. According to the acquired results (Figure 1

Synthesis of chiral 3-substituted 3-amino-2-oxindoles through enantioselective catalytic nucleophilic additions to isatin imines

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 1349–1369, doi:10.3762/bjoc.14.114

• catalytic asymmetric construction of the cyclic enaminone-based 3-substituted 3-amino-2-oxindole scaffold with potential bioactivity on the basis of enantioselective additions of cyclic enaminones to N-Boc-isatin imines [40]. As shown in Scheme 7, the addition of dimedone-derived enaminones 22 to a variety

• %) and good to high enantioselectivities (84–96% ee). The process was compatible with a wide range of N-Boc-isatin imines bearing various substituents, the electronic nature and position of which having no obvious effect on the enantioselectivity. Moreover, a variety of dimedone-derived enaminones

• bearing electronically different substituents at the ortho, meta and para-positions of the aniline moieties was compatible. The scope of this methodology could be extended to another type of enaminones, such as hydroxyfuran-2-one-derived ones 25, which afforded by reaction with N-Boc-isatin imines 3 the

Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• usage of 1.5 to 2.0 equivalents of the hypervalent iodine reagent 20b lowers the conclusive atom efficiencies. In another closely related procedure, Das and co-workers employed PIDA derivatives 20b for an aromatization–arylation cascade of exocyclic β-enaminones 27 [46]. Under basic reaction conditions

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• groups [23][27][28], C=C double [24][25][26], or C≡C triple [29][30][31][32] bonds in the structure of the initial molecule (Scheme 1). Intermolecular reaction of metal carbenes with thioamides usually generates thiocarbonyl ylides which leads for example to enaminones [14][33][34][35] or, in the

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• theory (DFT) for energetic and molecular orbital (MO) calculations. Keywords: 5-aminotetrazol; azide–tetrazole equilibrium; 2-azidopyrimidine; β-enaminones; tetrazolo[1,5-a]pyrimidine; trifluoromethylatedtetrazolo[1,5-a]pyrimidines; Introduction Tetrazolo[1,5-a]pyrimidines have attracted attention in

• atom of the enone, both soft sites of the starting materials [29]. In recent research, we developed an efficient method to obtain 1,2,4-triazolo[1,5-a]pyrimidines from the cyclocondensation reaction of 1,1,1-trifluoro-4-metoxy-3-alken-2-one or β-enaminones with 5-amino-1,2,4-triazole. The methodology

• -dimethylamino vinyl ketones, and the NCN block is 5-aminotetrazole. Results and Discussion Synthesis of tetrazolo[1,5-a]pyrimidines The β-dimethylamino vinyl ketones (β-enaminones) were synthesized using methodologies previously described by our research group [31]. In order to achieve better reaction

Transition-metal-free synthesis of 3-sulfenylated chromones via KIO₃-catalyzed radical C(sp²)–H sulfenylation

• Yanhui Guo,
• Shanshan Zhong,
• Li Wei and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2017, 13, 2017–2022, doi:10.3762/bjoc.13.199

• Yanhui Guo Shanshan Zhong Li Wei Jie-Ping Wan College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, P.R. China 10.3762/bjoc.13.199 Abstract The reactions between o-hydroxylphenyl-functionalized enaminones and sulfonyl hydrazines providing 3-sulfenylated

• ), prolonging the reaction time to 24 h was found to be capable of further improving the yield of 3a (entries 16 and 17, Table 1). To examine the scope of the reaction, enaminones 1 containing different functional groups as well as various sulfonyl hydrazines 2 were subjected to the optimized standard reaction

• conditions. As shown in Scheme 2, functional groups with different properties, including electron-withdrawing and electron-donating ones at the phenyl ring of the enaminones and the sulfonyl hydrazines exhibited tolerance to the reaction conditions. The 3-sulfenylated products were obtained in generally good

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• catalytic amount of Ce(IV) ammonium nitrate (CAN) [17], which had been previously pre-mixed for 30–60 min to ensure the complete generation of the intermediate bis-β-enaminones 5, were added to the reaction vessel, together with silver nitrate, and the mixture was again submitted to milling for an

New syntheses of (±)-tashiromine and (±)-epitashiromine via enaminone intermediates

• Darren L. Riley,
• Joseph P. Michael and
• Charles B. de Koning

Beilstein J. Org. Chem. 2016, 12, 2609–2613, doi:10.3762/bjoc.12.256

• /C-8 bond. In this article we describe further extensions to our route to substituted indolizidines, and an application to the synthesis of racemic tashiromine (1) and epitashiromine (2). Results and Discussion One of the most versatile methods for preparing the enaminones of interest is the

• indolizidine skeleton. To this end we chose to investigate the reaction of 3-(2-thioxo-1-pyrrolidinyl)propyl acetate (3), which we had previously used as a precursor to enaminones and indolizidines [28], with three different reaction partners, namely, α-bromoacetone, ethyl α-bromoacetate and α

• -halocarbonyl compounds afforded enaminones 7a and 7b in good yields (90–95%), but the reaction with α-bromoacetonitrile gave enaminonitrile 7c in only 44% yield. The deacetylation of 7a–c with potassium carbonate in methanol afforded the corresponding alcohols 8a–c in good yields (82–89%; Table 1). The data

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• [2,3,4-kl]acridines (the core structure of plakinidine C) from enaminones and 3-indolyl-3-hydroxyoxindoles through a cascade ring-opening/recyclization/methyl migration sequence (Scheme 61) [78]. The reactions proceeded well in MeCN in the presence of catalytic I2 (30 mol %) under an O2 atmosphere

• entry to polycyclic scaffolds for further biological screening. Similarly, Shi et al. established CPA-catalyzed highly enantioselective aza-ene reactions of cyclic enaminones with 3-indolyl-3-hydroxyoxindoles, incorporating enaminones and 3-indolyl-3-hydroxyoxindoles into C3-functionlized chiral indoles

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

• Hana Doušová,
• Radim Horák,
• Zdeňka Růžičková and
• Petr Šimůnek

Beilstein J. Org. Chem. 2015, 11, 884–892, doi:10.3762/bjoc.11.99

• catalytic hydrogenation of the corresponding quinolones 2 (Scheme 2) with yields not greater than 43%. In the present work, we introduce a quite different approach to the exocyclic enaminones 1 based on an intramolecular C–N cross-coupling of enaminones 3 (Scheme 2). Results and Discussion The synthesis of

• the starting substrates A simple retrosynthesis of enaminones 3 leads to the corresponding β-diketones 4 accessible through Claisen condensation of 3-phenylpropionic ester 5 with the appropriate acetophenone 6 (Scheme 3). The synthesis of ester 5 was accomplished according to Scheme 4. The classic

• ) indicates the presence of an intramolecular hydrogen bond N–H···O. The enaminones 3 therefore possess Z configuration on the C=C bond. The intramolecular C–N cross-coupling β-Enaminones and related polarized ethylenes (generally enamines substituted by EWG on β-carbon atom) belong among the rather neglected

A catalyst-free multicomponent domino sequence for the diastereoselective synthesis of (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]chromen-4-ones

• Pitchaimani Prasanna,
• Pethaiah Gunasekaran,
• Subbu Perumal and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2014, 10, 459–465, doi:10.3762/bjoc.10.43

• structural fragment, since enaminones are versatile starting materials in organic synthesis and are notably important for the synthesis of nitrogen heterocycles [25][26][27]. In particular, β-enaminoketones are endowed with electrophilic and nucleophilic reaction centers and have a versatile reactivity that

• our starting enaminones, namely 2a (Ar = Ph) and 2c (Ar = 3-NO2C6H4) with aniline under our standard reaction conditions (DMF, 130 °C) affords the corresponding compounds 4 after 3 h in 94% and 90% yields, respectively. As previously mentioned (Table 1), the nature of the solvent was found to be of