Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• carbonylative reduction approach of organic nitro compounds has been used for the synthesis of important industrial and pharmaceutical compounds such as indoles. In 1986, Cenini et al. reported a new synthetic method for indoles that involved 2-nitrostyrene derivatives. The reaction took place under drastic

• -b]indol-1-ones. Indole synthesis by deoxygenation reactions of nitro compounds reported by Cenini et al. [21]. Indole synthesis by reduction of nitro compounds: approach reported by Watanabe et al. [22]. Indole synthesis from o-nitrostyrene compounds as reported by Söderberg and co-workers [23

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• , application, and recycling of a new lipophilic cinchona squaramide organocatalyst. The synthesized lipophilic organocatalyst was applied in Michael additions. The catalyst was utilized to promote the Michael addition of cyclohexyl Meldrum’s acid to 4-chloro-trans-β-nitrostyrene (quantitative yield, up to 96

• addition of trans-β-nitrostyrene (12) and acetylacetone (13). Choosing the best solvent for the reaction is crucial, thus, solubility tests were carried out (Table 1). Since homogeneous catalysts usually exhibit higher activity and selectivity than their heterogeneous counterparts [27], our aim was to

• reaction could be used in the synthesis of several drugs to form a carbon–carbon bond in a stereoselective manner [6][35]. Our goal was to synthesize the chiral precursor 17 of baclofen (Scheme 3). To achieve this objective, we first planned to use Meldrum’s acid and 4-chloro-trans-β-nitrostyrene (16

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• and Discussion In order to explore the feasibility of the triple cascade reaction with acetaldehyde (2a) as a substrate, we tested the original reaction conditions reported by Enders using trans-β-nitrostyrene (3) and trans-cinnamaldehyde (4) as the other substrates (Table 1, entry 1). The reaction

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

• Pharmaceutical Sciences, Osaka University, Yamadaoka 1-6, Suita, Osaka 565-0871, Japan 10.3762/bjoc.19.67 Abstract Although nitrocyclopropanedicarboxylic acid esters are widely used in organic syntheses, nitrocyclopropanes with an acyl group have not yet been synthesized. When adducts of β-nitrostyrene and 1,3

• ) halogenation, and 3) ring closure (Scheme 2). β-Nitrostyrene 2 serves as an appropriate acceptor for conjugate addition by diethyl malonate (3a) to afford adduct 4a, in which the methine group flanked by two carbonyl groups is readily halogenated, and the subsequent intramolecular nucleophilic substitution by

• nitronic acid furnishes cyclopropane 1a (method a) [1][4][12][13]. Halogenated malonate 6a [7][14][15][16][17] and nitrostyrene 7 [18] can also be used as substrates in this protocol (methods b and c, respectively). In these methods, diesters are mostly used as 1,3-dicarbonyl compounds, with acetylacetone

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

• conjugate additions and allylic substitutions [15]. Given these developments, we posed the question of how would Zr enolates 133, formed by the corresponding conjugate addition, would react with highly reactive electrophiles. With typical electrophiles such as benzaldehyde or nitrostyrene no enolate

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• -nitrostyrene (7a) catalyzed by (S,R)-C2 (Scheme 3). The reaction in CH2Cl2 at 5 °C with Et3N as a base gave 45% of adduct 8a with 86:14 dr and 24:76 er for both diastereomers. Slightly better yields (63%) were achieved in CHCl3 at room temperature with Et3N or NMP as a base, but both diastereoselectivity as

• )benzene (7b). Hexanal (6b) reacted successfully with 4-fluoro-β-nitrostyrene (7c) and gave product 8d under all conditions tested (in solution, solvent-free, and ball-milling conditions, vide infra). Again, small amounts of catalyst (S,R)-C2 gave the best chemical yield. Catalyst (S,R)-C2 (3 mol %) in

• ) was reacted with 4-fluoro-β-nitrostyrene (7c). In the presence of catalyst (S,R)-C2 only traces of product 8f (THF/H2O, NMM as the base, and additive PhCO2H) were obtained (Scheme 3). Michael acceptors containing heterocyclic groups have been studied only sparingly, but the corresponding chiral

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• et al. They carried out asymmetric conjugate amination of tert-butylbenzyloxycarbamate (50) to β-nitrostyrene 51 under neutral phase-transfer conditions in the presence of chiral bifunctional tetraalkylammonium bromide (cat. 52) in water-rich biphasic solvent. The reaction proceeded with high ee

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• of just 13%. Nitroaldol reactions were also performed and nitrostyrene (74) was achieved with 54% selectivity (1:1 73/74) and 100% conversion at 90 °C. It is worth noting that the degree of production could be readily increased by numbering up of the hollow fibres which are bundled in the column

• comparable outcomes. A similar system was later described by Asefa et al. The authors packed a jacketed glass capillary microreactor with an amine-functionalised mesoporous silica (AP-T) pressed into small pellets (Scheme 22) [134]. The apparatus enabled the preparation of p-hydroxy-β-nitrostyrene (103) in

Nitroalkene reduction in deep eutectic solvents promoted by BH₃NH₃

• Chiara Faverio,
• Monica Fiorenza Boselli,
• Patricia Camarero Gonzalez,
• Alessandra Puglisi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2021, 17, 1041–1047, doi:10.3762/bjoc.17.83

• attention on the use of some choline chloride (ChCl)-based eutectic mixtures as reaction media. The reduction of β-nitrostyrene to afford (2-nitroethyl)benzene was selected as model reaction, and it was performed typically in the presence of 1 molar equiv of ammonia borane for 18 h at 60 °C (see Table 1

• -nitrostyrene (326 mg, 2 mmol) was suspended in the DES. Ammonia borane (62 mg, 2 mmol) was added to the suspension, and the reaction mixture was heated at 60 °C. After 18 h, the reaction mixture was cooled to room temperature, centrifuged, and the product was removed by liquid–liquid separation with a Pasteur

• pipette. The crude product was purified by column chromatography (silica as stationary phase; eluent: n-hexane/ethyl acetate). For the subsequent runs, fresh β-methyl-β-nitrostyrene (326 mg, 2 mmol) was suspended in the DES, and ammonia borane (1 equiv) was added to the mixture. The procedure is analogous

Application of the Meerwein reaction of 1,4-benzoquinone to a metal-free synthesis of benzofuropyridine analogues

• Rashmi Singh,
• Tomas Horsten,
• Rashmi Prakash,
• Swapan Dey and
• Wim Dehaen

Beilstein J. Org. Chem. 2021, 17, 977–982, doi:10.3762/bjoc.17.79

• nitrochromenobenzofuropyridine 21 was achieved after treatment of 16 with nitrostyrene in the presence of DABCO applying our previously reported ball milling procedure [40]. The synthesis of 22 was performed using the Perkin reaction [41]. The reaction of 16 with propionic anhydride and the corresponding sodium salt in the

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

• co-workers [50] demonstrated an aqueous phase, diastereoselective, multicomponent reaction involving substituted isatins 35, β-nitrostyrene 36 and benzylamine (20) or α-amino acids 37 using microwave irradiation to afford a library of spirooxindoles 38 in good yields under catalyst-free conditions

• addition between nitrostyrene adducts A and β-keto enamine B generated in situ consequently undergoes cyclization C and dehydration D to afford the desired product 62. PPA-SiO2 accelerates the reaction by enhancing the electrophilicity of the 1,3-diketones and the aldehydes by increasing the rate of

• generation of the β-enaminocarbonyl and nitrostyrene intermediates. Activation of Michael addition followed cyclization was catalyzed by silica-supported PPA-SiO2 (Scheme 23). Fused pyrroles have also been constructed by exploring the utility of a multicomponent reaction coupled with microwave irradiation

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• order to avoid the relatively long synthesis of the precursors we tried to change Br for another leaving group Y (Scheme 4). First, we prepared 3-chlorooxindole (1f) which is available from β-nitrostyrene and acetyl chloride under FeCl3 catalysis [41]. Unfortunately, the Eschenmoser coupling reaction

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• activation parameters. Furthermore, the synthetic utility of the cycloadducts obtained was demonstrated. Keywords: Diels–Alder reaction; fluorine; nitrostyrene; norbornene; stereochemistry; Introduction Organofluorine compounds play an exceptionally important role in various fields of science and

• of CPD with the model nitrostyrene 1h was simulated in silico to predict the reaction pathway, the reaction rate constants, and the activation enthalpies. Density functional theory calculations were conducted for the reactants, products, and transition states using the B3LYP [64][65][66] and M062X

• dispersion effects are not included, whereas M062X includes nonlocal effects of electronic dispersion [70][75]. We also demonstrate the preparation of norbornene structures substituted at the methylene bridge. The reaction of model nitrostyrene 1h with spiro[2.4]hepta-4,6-diene was carried out (Scheme 2). As

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• measurement of the yield and the diastereoselectivity was possible by NMR spectroscopy. The nitro-Michael reaction of 3 equivalents propanal (14) and β-nitrostyrene (15) with 25 mol % of 13a-H2 after 2 days at room temperature resulted in 45% yield of product 16 and a nearly 1:1 diastereomeric ratio (Table 2

One-pot and metal-free synthesis of 3-arylated-4-nitrophenols via polyfunctionalized cyclohexanones from β-nitrostyrenes

• Haruyasu Asahara,
• Minami Hiraishi and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2020, 16, 1830–1836, doi:10.3762/bjoc.16.150

• method toward the preparation of 3-arylated-4-nitrophenols. On the other hand, nitroalkenes possess an electron-deficient double bond, and hence, they serve as an excellent Michael acceptor and dienophile [12][13][14][15][16][17][18][19]. When β-nitrostyrene (1, Ar = Ph) is subjected to the Diels–Alder

• trimethylsiloxy group of the diene can be converted to a phenolic hydroxy group by hydrolysis) [20], followed by the oxidation and aromatization of the obtained cyclohexanone 4 (Scheme 1). Results and Discussion Heating an acetonitrile solution of nitrostyrene 1a with Danishefsky’s diene (2) at 60 °C for 18 h

• nitroalkene properties and consequently suppressed the Diels–Alder reaction with 2. It is noteworthy that not only the benzene ring, but also a heteroaromatic ring could be introduced into the nitrophenol framework by using this method (Table 3, entry 5). Conclusion β-Nitrostyrene 1a underwent a Diels–Alder

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• -hydroxyphthalimide (NHPI, OD22, similar to the benzophenone photocatalysts OD9 and OD10) can abstract an H atom from the aldehyde substrate 20.1. The resulting acyl radical adds to the (E)-β-nitrostyrene 20.2, and the following denitrosylation affords the chalcones 20.3. Alkenyl and aryl radical ions (radical

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• between diethyl malonate and nitrostyrene to afford only one of the two (S)-11 and (R)-11 enantiomers, depending on the redox state of the copper center. The reaction was run with a 5 mol % catalyst loading and a base (Et3N) and was compatible with different solvents (THF, MeCN, CH2Cl2 and hexane

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• Kharasch-type radical propagation reaction as the main pathway. Upon increasing the electron density by using 4-vinylanisole, we did see formation of the lactone product. When we used p-nitrostyrene, no formation of the desired products was observed at all. Based on the results described above we propose

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

• addition with a subsequent intramolecular cyclization catalyzed by Cu(BDC)MOF. Further, the LC–MS study of the reaction mixture has shown the imine formation to be the major pathway rather than β-nitrostyrene. The reaction involved a two-step reaction mechanism in which aza-Michael adduct 13 was formed in

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• Initially we carried out a screening of catalysts using the Ni(II) complexes 7a–h with chiral vicinal diamines L1–L8 (Figure 2) in a model reaction of 1-phenyl-2-(phenylsulfonyl)ethan-1-one (5a) with ω-nitrostyrene (6a). The results of the study are shown in Table 1. The Michael addition of the β

• 8a or 9a. Оne of the stereoisomers can be formed directly during the reaction. To test this hypothesis, we decided to study the evolution of dr on the course of reaction by 1H NMR spectroscopy (Figure 3). The reaction of sulfone 5a with ω-nitrostyrene (6a) was chosen as the model reaction. Conversion

• ). This study shows that the asymmetric addition of sulfone 5a to ω-nitrostyrene (6a) occurs enantio- and diastereoselectively and leads to isomer 8a, and the formation of 9a is explained by subsequent epimerization of 8a. The study of the reaction of various β-ketosulfones with nitroalkenes in the

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• asymmetric Michael addition of n-butanal to β-nitrostyrene that was used as a model reaction. This work supports the potential of multicomponent reactions towards the assembly of catalysts and their simultaneous functionalization for immobilization. Keywords: flow chemistry; heterogeneous catalysis

• -butanal to trans-β-nitrostyrene was implemented. During the initial screening, standard reaction conditions comprising the use of 10 mol % of catalyst, toluene as solvent and room temperature were chosen. As shown in Table 1, PFA – used as control – did not afford the Michael product (Table 1, entry 1

• continuous-flow conditions started with the optimization of the flow rate. Initially, a solution of β-nitrostyrene (1 equiv, 0.25 M) and n-butanal (3 equiv, 0.75 M) in toluene was pumped using a syringe-pump at 2.5 µL·min−1 (τ = 140 min, Figure 1, top). The concentration was chosen by considering the

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• reaction was further optimized using salicylaldehyde (1a), β-nitrostyrene (2a) and benzyl azide (3a) as model substrates (see Supporting Information File 1, pages S4–S8 for full description of the optimization study). The optimized conditions for the one-pot three-component reaction were determined to be 1

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• the new chiral amino-substituted thioureas [33][39]. For this, the Michael addition reaction of acetylacetone (8) to β-nitrostyrene (7a) was chosen as the model reaction to evaluate the efficiency of compounds 1–4 as chiral organocatalysts (Table 1, entries 1–4). From Table 1, it can be seen that the

• nitrostyrene 7a lacking substituents has minimal steric hindrance and tends to bind with the calixarene cavity by supramolecular host–guest interactions which could further improve the enantioselectivity. In addition, electronic effects of the substituents on the aromatic ring showed a significant influence on

• the groups present on the aromatic ring. We propose the following plausible synergistic catalytic mechanism (Scheme 3). First, the two oxygen atoms of the nitro group in the nitrostyrene are activated through double hydrogen bonding with the thiourea group, while the benzene ring is held by a

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• -deficient unsaturated carbonyl compounds (Scheme 13). In general, terminal alkenes were found to undergo 1,2-difluorination 42a–c. The reaction of internal alkenes usually afforded the syn-difluorination products 42d and 42e. However, the opposite result was observed in the reaction of the o-nitrostyrene

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• -benzyloxyphenethylamine, which gave the 7-O-benzyl derivative of alkaloid 1 in 27% yield. The required precursor is available from commercially available precursor 2 via a nitrostyrene intermediate in three steps in 45% overall yield [13]. In conclusion, no efficient approach to this “simple” alkaloid 1 has yet been