CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• chalcone gave low regioselectivities with mixed Markovnikov and anti-Markovnikov products. The CF3 radical is electrophilic in nature and, as such, not prone to readily react with electron-deficient alkenes. Nevertheless, Lefebvre, Hoffmann and Rueping reported that N-substituted maleimides, maleic

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• maleimides in toluene provided a ready access to the fused ring-system 6a–c in excellent yields (81–91%; Scheme 3, middle). Finally, the [4 + 1]-cycloaddition with nitrenes was carried out (Scheme 3, right). To attain this transformation the required nitrene was formed in situ from an iminoiodinane precursor

Thiazol-4-one derivatives from the reaction of monosubstituted thioureas with maleimides: structures and factors determining the selectivity and tautomeric equilibrium in solution

• Alena S. Pankova,
• Pavel R. Golubev,
• Alexander F. Khlebnikov,
• Alexander Yu. Ivanov and
• Mikhail A. Kuznetsov

Beilstein J. Org. Chem. 2016, 12, 2563–2569, doi:10.3762/bjoc.12.251

• . 26, Saint Petersburg, 198504, Russia 10.3762/bjoc.12.251 Abstract 2-(Alkyl(aryl)amino)thiazol-4(5H)-ones can regioselectively be prepared from monoalkyl(aryl)thioureas and maleimides. In solution, the former heterocycles exist in a tautomeric equilibrium with 2-(alkyl(aryl)imino)thiazolidin-4-ones

• and the substituent on the exocyclic nitrogen atom governs the ratio of these tautomers. Isomers with the alkyl group in the endocyclic position can be obtained from N-methyl(ethyl)thioureas. 2D NMR spectroscopy and DFT calculations rationalize experimental results. Keywords: maleimides

• derivatives with various dielectrophiles [8]. In particular, the addition of monoalkyl(aryl)thioureas to N-substituted maleimides provides the corresponding thiazolidinylacetamides. First described by Marrian in 1949 [9] and later developed further by Augustin and co-workers [10][11], a plausible mechanism

Stereoselective synthesis of fused tetrahydroquinazolines through one-pot double [3 + 2] dipolar cycloadditions followed by [5 + 1] annulation

• Xiaofeng Zhang,
• Kenny Pham,
• Shuai Liu,
• Marc Legris,
• Alex Muthengi,
• Jerry P. Jasinski and
• Wei Zhang

Beilstein J. Org. Chem. 2016, 12, 2204–2210, doi:10.3762/bjoc.12.211

• ). Compound 7b was an exception, which was obtained in a trace amount. It was found that replacing maleimides 6 with other activated alkenes such as dimethyl maleate, benzoquinone, naphthalene-1,4-dione, and maleonitrile failed to afford products 7q–t, probably due to unfavorable stereoelectronic effects

• second [3 + 2] cycloaddition of azide compounds 2 with maleimides and sequential denitrogenation to products 7 is proposed in Scheme 2. 1,5-Diamino compounds 7 generated by one-pot reactions are good substrates for [5 + 1] annulation with aldehydes to form tetrahydroquinazolines 1 [34][35]. After

A chiral analog of the bicyclic guanidine TBD: synthesis, structure and Brønsted base catalysis

• Mariano Goldberg,
• Denis Sartakov,
• Jan W. Bats,
• Michael Bolte and
• Michael W. Göbel

Beilstein J. Org. Chem. 2016, 12, 1870–1876, doi:10.3762/bjoc.12.176

• of the guanidinium benzoate salt the six membered rings of 10 adopt conformations close to an envelope with the phenyl substituents in pseudo-axial positions. The unprotonated guanidine 10 catalyzes Diels–Alder reactions of anthrones and maleimides (25–30% ee). It also promotes as a strong Brønsted

• molecule are also connected by a number of very weak intermolecular C–H···π (phenyl) and C–H···O contacts (see Supporting Information File 2). The chiral guanidine 10 was tested as a Brønsted base catalyst to promote the reaction of anthrones 20 or 21 with maleimides 22–24 (Scheme 2) [19][25][26][27][28

• successfully used as catalysts for anthrone maleimide cycloadditions [29][30][31][32][33][34][35]. In the presence of 10, dichloroanthrone 21 reacted with maleimides 22 and 23 to produce exclusively cycloadducts 26 and 27. In contrast, a mixture of 25 and 28 resulted from the reaction of anthrone 20 and N

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• processes (e.g., N-alkyl maleimides, ε = ~700 M−1 cm−1) [62] lead to more efficient light penetration in batch reactions and therefore only show a limited benefit of using flow reactors for such purposes. On the other hand, a 1 mM solution of methylene blue exhibits total absorption (>99.9%) at 0.35 mm

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

• . found that β-isocupreidine (β-ICD, cat. 22) can efficiently catalyze the Morita–Baylis–Hillman (MBH) reaction of isatins with maleimides to generate the 3-substituted 3-hydroxyoxindoles in excellent yields (up to 96% yield) and with excellent enantioselectivity (up to >99% ee) under mild conditions

• maleimides, affording the corresponding products in excellent yields (up to 98% yield) and with excellent enantioselectivity (up to 94% ee, Scheme 37) [54]. Additionally, other activated alkenes such as methyl and ethyl acrylates and acrolein reacted smoothly with 7-azaisatins, giving the corresponding

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• substituted maleimides 53, which in the presence of the above mentioned catalyst, afforded the highly substituted endo-adducts 54 with high yield and enantiomeric excess (Scheme 17). In this approach, the cis orientation of the hydroxy and cyclopentylamine groups of the catalyst was crucial to achieve high

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• tertiary amine-thiourea 56 was reported by Bernardi, Ricci and co-workers for the Diels–Alder reaction of 3-vinylindoles 51 (Scheme 18) [29]. The authors utilized either maleimides 52 or quinones 53 as the dienophile, affording the products 54 and 55 in excellent yields and enantioselectivities, after

• rings initiated by oxy/aza/sulfa-Michael addition In 2007, Wang and co-workers utilized 2-mercaptobenzaldehydes 163 and α,β-unsaturated systems as Michael acceptors, such as α,β-unsaturated oxazolidinones 164 and maleimides 52, in order to catalyze Michael aldol cascades to construct versatile

• loading. The authors proposed a bifunctional mode of activation. More specifically, the thiourea moiety activates the maleimide through hydrogen-bonding and the tertiary amine recognizes the thiol group, again through hydrogen-bonding, and orients the thiol attacking from the Si-face of the maleimides 52

Application of 7-azaisatins in enantioselective Morita–Baylis–Hillman reaction

• Qing He,
• Gu Zhan,
• Wei Du and
• Ying-Chun Chen

Beilstein J. Org. Chem. 2016, 12, 309–313, doi:10.3762/bjoc.12.33

• in diverse biologically active substances. Here 7-azaisatins turned out to be more efficient electrophiles than the analogous isatins in the enantioselective Morita–Baylis–Hillman (MBH) reactions with maleimides using a bifunctional tertiary amine, β-isocupreidine (β-ICD), as the catalyst. This route

• stereocontrol [6][7][8][9][10][11][12]. Maleimides are also good nucleophilic precursors in the MBH reactions and in 2013, Chimni developed an asymmetric MBH reaction of isatins and maleimides with excellent enantioselectivity [13]. Later, the same group expanded this strategy to isatin-derived ketimines under

• addition, 7-azaisatins were also applied in asymmetric synthesis [18][19]. Therefore, with our continuing interest in the catalytic application of bifunctional β-ICD [20][21][22][23], herein we report the enantioselective MBH reaction of 7-azaisatins with maleimides. A series of 3-hydroxy-7-aza-2-oxindoles

Preparative semiconductor photoredox catalysis: An emerging theme in organic synthesis

• David W. Manley and
• John C. Walton

Beilstein J. Org. Chem. 2015, 11, 1570–1582, doi:10.3762/bjoc.11.173

• functionalized carboxylic acids that take part in decarboxylative additions to maleimides is presented in Scheme 5. Reasonable yields of adducts were obtained for alkyl radicals with α-alkoxy substituents. Two diastereomers of 22 as a 1:1 mixture were obtained from 2-tetrahydrofuroic acid in a very pleasing

• catalysts. We observed that during TiO2 promoted alkylations of maleimides with carboxylic acids, the products always included significant amounts of succinimides, so simple hydrogenation had occurred [53][54]. Evidently the maleimides operated as electron sinks in two sequential reduction–protonations, in

• hole-scavenger N-phenylsuccinimide was indeed produced almost quantitatively. Good to excellent yields (82–94%) of the corresponding succinimides were obtained from a range of N-substituted maleimides (Scheme 13) [79]. Exceptions were starting maleimides with 3- and or 4-substituents on their C=C

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• excellent yield (Table 2, entries 11 and 12). Interestingly, the N-phenyl analogue of Captan, a commercially used fungicide could be synthesized in excellent yield (Table 2, entry 12) [18][19]. The reaction of aromatic amines with unsaturated anhydrides to form maleimides was investigated (Table 3). Aniline

• , p-toluidine and p-cyanoaniline furnished the corresponding maleimides from maleic anhydride (Table 3, entries 1–3). 4,4’-Oxydianiline and maleic anhydride also reacted well to provide 4,4’-bis(maleimidodiphenyl) ether in excellent yield (Table 3, entry 4). This bismaleimide and its analogues are

Eosin Y-catalyzed visible-light-mediated aerobic oxidative cyclization of N,N-dimethylanilines with maleimides

• Zhongwei Liang,
• Song Xu,
• Wenyan Tian and
• Ronghua Zhang

Beilstein J. Org. Chem. 2015, 11, 425–430, doi:10.3762/bjoc.11.48

• Engineering, Jiaxing University, Jiahang Road 118, Zhejiang 314001, China 10.3762/bjoc.11.48 Abstract A novel and simple strategy for the efficient synthesis of the corresponding tetrahydroquinolines from N,N-dimethylanilines and maleimides using visible light in an air atmosphere in the presence of Eosin Y

• tends to form the iminium ion by one electron oxidation (Scheme 1) [39][40][41]. In the context of this research background, we investigated the α-aminoalkyl radical route to achieve the aerobic oxidative cyclization of N,N-dimethylanilines with maleimides to form the corresponding tetrahydroquinoline

• form N,N-dimethylanilines 1 and maleimides 2 is depicted in Scheme 3. On absorption of visible light, the ground state of Eosin Y (EY) is induced to its single excited state (1EY*), which moves to its more stable triplet excited state (3EY*) through inter system crossing (ISC) [46][47]. 3EY* may

A simple and efficient method for the preparation of 5-hydroxy-3-acyltetramic acids

• Johanna Trenner and
• Evgeny V. Prusov

Beilstein J. Org. Chem. 2015, 11, 323–327, doi:10.3762/bjoc.11.37

• chemoselective reduction of the corresponding maleimides [5] and oxidation of pyrrolinones was reported by Clayden [6]. Therefore, we decided to develop a simple method to produce these interesting compounds. At first we prepared three nitrogen-protected 3-acyltetramic acids (7–9) according to the Matsuo [7

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• low to moderate enantioselectivities. In 2012, Lu, Shi, and co-workers found that the dipeptide-based phosphine H10 was also quite effective as a chiral catalyst for [3 + 2] annulations of various maleimides with allenoates (Scheme 25) [56]. They obtained a wide range of bicyclic cyclopentenes in good

• to excellent yields. N-Alkyl-substituted maleimides were converted to cyclopentenes in high ee, while N-aryl-substituted maleimides underwent the reaction with low to moderate enantioselectivity. Using the multifunctional chiral phosphine G6, featuring a binaphthyl skeleton and bearing a thiourea

• corresponding γ-cycloadduct as the major product in 92% yield, with 9:1 dr and 74% ee [77]. Using the amino acid-derived chiral phosphine catalyst H11, Lu and co-workers performed asymmetric [3 + 2] annulations between MBH carbonates and maleimides, obtaining access to a wide range of bicyclic imides in

Visible-light photoredox catalyzed synthesis of pyrroloisoquinolines via organocatalytic oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade with Rose Bengal

• Carlos Vila,
• Jonathan Lau and
• Magnus Rueping

Beilstein J. Org. Chem. 2014, 10, 1233–1238, doi:10.3762/bjoc.10.122

• ), cyano (1d) or aromatic ketone (1e) were reacted with N-methylmaleimide (2a) and gave the corresponding products 3 in moderate to good yields. In addition, different N-substituted maleimides were tested under the optimized reaction conditions to give the corresponding products with good yields

• visible-light. This protocol offers a “green” and straightforward synthesis of pyrrolo[2,1-a]isoquinolines starting from readily available maleimides and tetrahydroisoquinolines. Further investigations to expand the scope and potential of this methodology are underway in our laboratory. Representative

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• studies started with the preparation (Scheme 1 and Scheme 2) of maleimides 4a–c employing maleic anhydride (1) and different aromatic amines 2a–c, and of furo[3,2-h]quinoliniums 9a–d from 5-chloro-8-hydroxy-7-iodoquinoline 5 [19][24]. However, attempted condensation of 4a with the 1,3-dipole generated in

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• anhydride or maleimides, at relatively high temperatures (80 °C in toluene) to afford exclusively the cis-isomers (Scheme 1). The resulting cycloadducts, which contain an allylboronate functionality, then reacted with aldehydes to afford the corresponding homoallylic alcohols with high diastereoselectivity

• -component adducts were isolated in good yields up to 92%. A single diastereomer was detected with maleimides; the diastereoselectivity being lower with methyl acrylate and vinyl oxazolidinone (Scheme 7). A one-pot, palladium-mediated cycloisomerization of ene-ynes 5 was applied to the synthesis of the

• and co-workers described metal-catalysed tandem Diels–Alder/hydrolysis reactions of 2-boron-substituted 1,3-dienes [54][55]. Boron-dienes containing various ligands reacted with maleimides in the presence of rhodium and copper catalysts using BINAP as ligand (Scheme 15). NMR analysis of the crude

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• nonnatural α-amino acids [11][12][13], more than fifteen isatins [14], and 1,3-dipolarophiles, e.g. α,β-unsaturated ketones [15][16][17], maleimides [18][19], benzo[b]thiophene-1,1-dioxide [20], bis(arylmethylidene)acetones and -cycloalkanones [21][22], 1,4-naphthoquinone [23], arylidenemalonodinitriles [24

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• , Universidad del País Vasco, Apdo. 1072, E-20018 San Sebastián, Spain IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain 10.3762/bjoc.9.280 Abstract The 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(Sa

• )-Binap·AuTFA]2. The alanine-derived oxazolone only reacts with tert-butyl acrylate giving anomalous regiochemistry, which is explained and supported by Natural Resonance Theory and Nucleus Independent Chemical Shifts calculations. The origin of the high enantiodiscrimination observed with maleimides and tert

• electrophilic alkenes have not been exploited. Toste´s group published an efficient 1,3-dipolar cycloaddition (1,3-DC) between alanine, phenylalanine and allylglycine derived azlactones with maleimides and acrylates employing dimetallic (S)-Cy-Segphos(AuOBz)2 complex 1 as a catalyst (2 mol %) in the absence of

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• tissue [20][21]. Therefore, designed prodrugs have a higher antitumor efficacy in vivo than drugs. Furthermore, maleimides possess strong antifungal activities against important human opportunistic pathogenic fungi. These antifungal drugs appear to be excellent candidates for further development [22][23

Automated three-component synthesis of a library of γ-lactams

• Erik Fenster,
• David Hill,
• Oliver Reiser and
• Jeffrey Aubé

Beilstein J. Org. Chem. 2012, 8, 1804–1813, doi:10.3762/bjoc.8.206

• , Germany 10.3762/bjoc.8.206 Abstract A three-component method for the synthesis of γ-lactams from commercially available maleimides, aldehydes, and amines was adapted to parallel library synthesis. Improvements to the chemistry over previous efforts include the optimization of the method to a one-pot

• been significant in the treatment of epilepsy [6][7], HIV [8][9], neurodegenerative disease and depression [10][11]. Having identified the lactam ring as a target of opportunity in chemical-screening efforts, we previously reported a method to prepare γ-lactams from readily available maleimides

• addition of enolizable aldehydes to maleimides in the original method suggested the possibility of producing chiral γ-lactams through the use of a chiral proline-like organocatalysts. In fact, Córdova and co-workers have previously established a protocol for such a process [13]. Based on this initial

Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines

• Chittaranjan Bhanja,
• Satyaban Jena,
• Sabita Nayak and
• Seetaram Mohapatra

Beilstein J. Org. Chem. 2012, 8, 1668–1694, doi:10.3762/bjoc.8.191

• bioactive succinimide-containing benzothiochromenes by condensation of 2-mercaptobenzaldehydes 34 with maleimides 42 catalyzed by a bifunctional chiral amine thiourea XXXVII. Mechanistically, the reaction proceeded through a hydrogen-bond-mediated activation mechanism by using 1 mol % catalyst loading

• α,β-unsaturated oxazolidinones, as presented by Wang and co-workers. Domino Michael–aldol reaction of 2-mercaptobenzaldehydes with maleimides catalyzed by cinchona alkaloid thiourea, as reported by Wang’s group. Domino thio-Michael–aldol reaction between 2-mercaptoacetophenone and enals developed by

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• bicyclic guanidines [7][9][12]. Xiao et al. reported the addition of nitroalkanes to 4-oxo-enoates, using chiral urea derivatives [7]. Miura et al. achieved an asymmetric addition of α,α-disubstituted aldehydes to maleimides catalyzed by primary amine thiourea organocatalyst [13]. Wang et al. reported the