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

• -mediated domino reaction of chromone-3-carboxaldehydes and amines [41], Pd-catalyzed redox-neutral C–N coupling reaction of iminoquinones with electron-deficient alkenes [42], NH3 insertion into o‑haloarylynones [43], gold(III)-catalyzed azide-yne cyclization [44], Michael/Truce-Smiles rearrangement

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• elucidation of a new polyketide 1 and a new acetylated alternariol derivative 2 as well as fifteen known compounds including three alternariol derivatives 3–5, one chromone 6, one biphenyl 7, seven cytochalasins 8–14, two cytosporones 15 and 16, and one macrolide 17 from the endophytic fungus, Diaporthe

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

• benzaldehyde (51) (Scheme 13a). Related to this work, Feringa´s team realized also the conjugate addition to chromone (53) [44]. The enolate was again trapped with benzaldehyde in an aldol reaction (Scheme 13b). Naphthol derivatives 55 bearing an α,β-unsaturated ester group undergo a copper(I)-catalyzed

• of heterocyclic enolates 108 generated from coumarin and chromone [65]. The high enantio- and diastereoselectivity of these transformations were ensured by a Josiphos-type ferrocene ligand. The reaction of chiral metal enolates with onium compounds enabled the installation of structurally attractive

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• group (101), chromone derivatives 102 were formed. On the introduction of the methylene moiety in between the aryl and methoxy group, 103 yielded isofuran derivatives 104 due to the change in regioselectivity during the cyclization. Dihydronapthalenes 106 were synthesized by cyclization of the

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• and enantioselectivity (49%; 57% ee; entry 4, Table 22) [48]. Finally, the catalytic system failed in the addition reaction with 2-methylchromone and did not yield the expected product, however, it proved to be highly effective for the addition reaction to unsubstituted chromone (91%; 94% ee; entry 5

• chromone derivative for the total syntheses of (−)-caesalpinnone A and (−)-caesalpinflavan B (Scheme 12) [9]. Mechanistic studies of this catalytic system were also made by Stoltz’s group. A linear relationship between the ee of the catalyst and the product has been found [48]. That means that the

• for the addition of phenylboronic acid to 2-cyclohexenone and chromone (Scheme 25) [61] was proposed by Tamura et al. in 2017. Excellent conversions and enantioselectivities (96–97%; 94–97% ee) were achieved for both studied substrates. However, a further use of this ligand has not been published yet

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• biologically interesting chromone skeleton was realized by PhIO-mediated dehydrogenation of chromanones under mild conditions. Interestingly, this method also found application in the synthesis of the naturally occurring frutinone A. Keywords: chromanone; chromone; dehydrogenation; frutinone A; PhIO

• ; Introduction The chromone system and its derivatives are an important class of heterocyclic compounds, the skeleton of which widely exists in a variety of natural products and medicinal agents [1][2][3]. It was found that chromone derivatives exhibit a wide range of pharmacological effects, including

• antibacterical [4], antifungal [5][6], anticancer [7], antioxidant [8], anti-HIV [9], antiulcer, immunostimulator [10], anti-inflammatory [11], as well as biocidal [12], wound-healing [13], and immune-stimulatory activities [14]. For instance, flavoxate [15][16] is a chromone derivative that was employed as an

Efficient synthesis of pyrazolopyridines containing a chromane backbone through domino reaction

• Razieh Navari,
• Saeed Balalaie,
• Saber Mehrparvar,
• Fatemeh Darvish,
• Frank Rominger,
• Fatima Hamdan and
• Sattar Mirzaie

Beilstein J. Org. Chem. 2019, 15, 874–880, doi:10.3762/bjoc.15.85

• Tietze and were applied for the synthesis of complicated scaffolds [7][8][9]. The selection of a suitable starting material and designing a post-transformational reaction is a key point for the synthesis of complex molecules through the designing of domino reactions [10]. Chromone derivatives have been

• construct fused heterocyclic skeletons [37][38][39][40], we describe the synthesis of pyrazolopyridines 4a–m containing a chromone moiety (Scheme 1). The synthetic approach was based on a domino reaction of (arylhydrazono)methyl-4H-chromen-4-one 1a–g, primary amines 2a–c, and malononitrile (3) in the

• (1.2 mmol), malononitile (1.2 mmol), Et3N (40 mmol %) in 3 mL ethanol at room temperature for 8–12 h. Structures of synthesized compounds 5a–d. Synthesis of pyrazolopyridines containing chromone 4a–m through a multicomponent reaction. The proposed mechanism for the synthesis of pyrazolopyridines

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• aldehydes, chromone aldehydes, and fluorene aldehydes (Ar2CHO) and coumarins (Ar3) in 1:1:1 ratio to form the corresponding tris(heteroaryl)methanes (Ar1Ar2Ar3)CH along with (Ar1Ar1Ar2)CH triads. A series of new 2:1 triads were also synthesized by coupling substituted indoles with Ar2CHO. The coupling

• new structure. This concept has recently received attention by the pharmaceutical industry because it provides new options to develop more specific drugs for the treatment of persistent and challenging pathologies [27][28] (Scheme 1). The indole, coumarin, quinoline, chromone and fluorene moieties are

• ternary heteroarylmethane-inspired hybrids by coupling diversely substituted indoles (Ar1) with quinoline aldehydes, quinolone aldehydes, chromone aldehydes, and fluorene aldehydes (Ar2CHO) and coumarins (Ar3) in 1:1:1 ratio by simple reflux in ethanol solvent to form the corresponding highly crowded tris

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• the yields and the enantiomeric excess. In a third reaction, the 1,4 addition of silyl keten acetals 11 to chromone 20 is investigated (Table 11, Scheme 8). Chromone 20 is first transformed to the oxonium ion pair 21. Catalyst BIFOXSi(OH)2 (9) binds the triflate anion via hydrogen bonding and leaves

• used for the C–C coupling in the N-acyl Mannich reaction with activated isochinolin 10, 1-chloroisochroman (18) and chromone 21 with different silyl ketene acetals. Due to more efficient bifunctional Si(OH)2-hydrogen bonding, silandiol 9 tops chlorosilanol 8, also on catalytic application

• NaOMe (0.2 mL, 0.5 M in MeOH), concentrated in vacuo and purified by silica gel flash column chromatography (n-hexane/Et2O 9:1). The enantiomeric excess is determined by chiral HPLC analysis (see Supporting Information File 1). General procedure for addition of silyl ketene acetals 11 to chromone 20 to

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• Michael addition pathway (see Figure 1b) [6]. Prompted by the interest of developing novel light-driven microfluidic methods for the construction of biologically relevant molecular scaffolds, we investigated the reaction between MBP 1 and 3-unsubstituted coumarin (2a) and chromone (3a, Figure 1c). It was

• , producing only traces of the expected sulfur-containing adduct 4i. As a matter of fact, compound 2e showed a high tendency to undergo a light-promoted [2 + 2] dimerization reaction, thus preventing the envisaged [4 + 2] cycloaddition pathway [13]. Next, the chromone scaffold 3a, which is a precursor of

• through a [4 + 2] cycloaddition manifold. b) Light-driven reaction between 2-MBP A and 3-substituted coumarin D for the synthesis of E through a Michael addition manifold. c) Light-driven reaction between 2-MBPs 1 and coumarin (2a) or chromone (3a) for the synthesis of privileged tetracyclic scaffolds 4

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• ’-ArH, aniline), 7.97 (d, J = 8,8 Hz, 1H, ArH, 5-chromone), 7.72 (s 1H, 6-uracil), 7.39 (s, 1H, ArH, 8-chromone), 7.07 (d, J = 9,3 Hz, 1H, ArH, 6-chromone), 6.85 (d, J = 8.6 Hz, 2H, 3’-ArH, aniline), 5.30 (s, 2H, CH2), 5.19 (s, 2H, CH2), 3.02 (s, 6H, CH3); 13C NMR (126 MHz, DMSO) δ 171.46 (C=Ochromone

• ), 163.64 (C=O6-uracill), 161.90 (CAr-O), 155.98 (CAr-O), 151.16 (C=O2-uracil), 150.85 (C4’-Ar, aniline), 146.17 (CAr-O), 142.98 (CHAr, triazole), 141.70 (CH4-uracil), 136.82 (C-OHchromone), 128.64 (2CH2’-Ar, aniline), 125.96 (CHAr, chromone), 124.83 (CHAr, triazole), 118.06 (CAr, chromone), 115.42 (CAr

• , chromone), 114.46 (CHAr, chromone), 111.37 (2CH3’-Ar, aniline), 106.18 (C5-uracil), 101.15 (CHAr, chromone), 61.75 (CH2-O), 45.90 (CH2-N), 40.02 (CH3); HRMS calcd. for [M + H+]: 503.1679; found: 503.1675. Fluorescence measurements All the spectroscopic experiments were carried out at 25 °C. In all

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

• chromones via domino chromone ring construction and C(sp2)–H bond sulfenylation have been achieved under transition-metal-free conditions by using KIO3 as the only catalyst. Keywords: C–H sulfenylation; chromones; domino reaction; free-radical; transition-metal-free; Introduction The C–S bond-forming

• readily synthesized with several different transition-metal-free C–H cross-coupling approaches. Zhou and co-workers reported the NH4I-promoted synthesis of 3-sulfenylated chromones via the direct chromone C–H sulfenylation by using different sulfur sources (A, Scheme 1) [38][39]. Recently, our continuous

•  1) [42]. Subsequently, Braga et al. reported a similar catalytic 3-sulfenylchromone synthesis by employing disfulfides as the sulfenyl sources (B, Scheme 1) [43]. Although the efficiency and application scope of the known routes are fine, the cost and limited variation on chromone substrates and/or

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• are based on using functionalized indoles, thiophenes, furans or chromone precursors, which require several steps to be prepared. Results and Discussion In this paper we wish to report a convenient, short and robust approach to 8-alkyl-2-(het)arylthieno[2,3-b]indoles from 1-alkylisatins and the

Binding mode and free energy prediction of fisetin/β-cyclodextrin inclusion complexes

• Bodee Nutho,
• Wasinee Khuntawee,
• Chompoonut Rungnim,
• Piamsook Pongsawasdi,
• Peter Wolschann,
• Alfred Karpfen,
• Nawee Kungwan and
• Thanyada Rungrotmongkol

Beilstein J. Org. Chem. 2014, 10, 2789–2799, doi:10.3762/bjoc.10.296

• docking suggested four possible fisetin orientations in the cavity through its chromone or phenyl ring with two different geometries of fisetin due to the rotatable bond between the two rings. From the multiple MD results, the phenyl ring of fisetin favours its inclusion into the β-CD cavity, whilst less

• binding or even unbinding preference was observed in the complexes where the larger chromone ring is located in the cavity. All MM- and QM-PBSA/GBSA free energy predictions supported the more stable fisetin/β-CD complex of the bound phenyl ring. Van der Waals interaction is the key force in forming the

• complex [33] suggested that the chromone ring (A-ring defined in Figure 1) of fisetin inserted into the β-CD hydrophobic cavity leads to a more stable complex than the insertion of the phenyl ring (B-ring). This is in contrast to the QM studies based on the SAM1, B3LYP and MPW1PW91 methods [28]. Since in

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

• ; Introduction Chromones are widely present in nature, especially in the plant kingdom, and a wide variety of useful biological properties are associated with them [1][2]. Chromone derivatives act as effective tyrosine and protein kinase C inhibitors [3] and display antifungal [4][5], antimycobacterial [6

• ], antiviral [7], antihypertensive [8], anti-oxidant [9][10][11][12], HIV-inhibitory [13], anti-inflammatory [14][15], immunomodulatory [16], antithrombotic [17], and anticancer [18][19][20] activities. Furthermore, some chromone derivatives have been identified as suitable fluorophores for live cell imaging

• [21]. In view of its importance chromone has emerged as a pharmacophore in drug discovery programmes, leading to several drugs in the market (e.g. cromolyn and nedocromil) and thereby continuing to draw the attention of synthetic organic and medicinal chemists [22][23][24]. However, there are