Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• trifunctional electrophiles and are useful building blocks for the introduction of a three carbon fragment into the resulting molecule. Thus, the reaction of enol ethers with hydrazines produces pyrazoles, with amidines pyrimidines, with hydroxylamine isoxazoles, and with anilines quinolines/ones are formed [2

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• as a powerful tool for the synthesis of medium-sized libraries of bioactive compounds. Thus, straightforward syntheses of 1,3-disubstituted-1,2-dihydroisoquinolines have been achieved by three-component reactions between alkynylbenzaldehydes 25 (γ-carbonylalkyne), primary amines 26 (mainly anilines

• electron-rich and electron-poor anilines are suitable partners for these reactions, whereas alkylamines and benzylamine gave worse results. Moreover, the third partner (Nu in Scheme 19) is limited to one substrate as in the reaction employing diethyl phosphite (32). Indoles 30 and imidazoles 31 can bear

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

• Madrid, Spain 10.3762/bjoc.10.43 Abstract The three-component domino reactions of (E)-3-(dimethylamino)-1-arylprop-2-en-1-ones, 3-formylchromone and anilines under catalyst-free conditions afforded a library of novel (E)-3-(2-arylcarbonyl-3-(arylamino)allyl)-4H-chromen-4-ones in good to excellent yields

• transformations [43][44][45][46][47][48][49][50][51][52][53][54]. In order to achieve our goal, we embarked on the study of the three-component reactions between 3-formylchromone (1), (E)-3-(dimethylamino)-1-arylprop-2-en-1-ones 2 and anilines 3, which we expected to furnish novel (E)-3-[2-arylcarbonyl-3

• substituted anilines 3 were performed under the optimal conditions (equimolecular amounts, DMF at 130 °C) and were completed in 6–7 h. After completion of the reaction, removal of the solvent and purification of the residue by column chromatography, (E)-3-[2-arylcarbonyl-3-(arylamino)allyl]-4H-chromen-4-ones

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• ][46][47][48][49][50][51] and synthesized them together with new functionalized 2-alkynylanilines to evaluate the efficiency of the gold catalytic system. Scope and limitations of the catalytic system The prepared 2-substituted anilines were then engaged in the cycloisomerization/fluorination process

• in the presence of the Au(I) cationic catalyst or the Au(III) catalyst (Table 2, conditions A and B). The anilines 1b–1f were subjected to conditions A and B at room temperature or refluxing ethanol. Under conditions A, the NaAuCl4·2H2O catalyst operated smoothly and Selectfluor (3 equiv) was added

• the reactivity of anilines 1a–1i in the presence of NaAuCl4·H2O complex in ethanol and the formation of 8 in the presence of 1 equivalent of Selectfluor, we decided to modify our initial procedure to selectively prepare 3-fluoro-2-aryl-indoles. We found that the cyclization of various unprotected

Continuous flow nitration in miniaturized devices

• Amol A. Kulkarni

Beilstein J. Org. Chem. 2014, 10, 405–424, doi:10.3762/bjoc.10.38

• unsafe, yet the range of conversion and the yields that are achieved will be different depending upon the mechanism. In general, the dinitroaniline derivatives are produced by nitration of anilines. Chen et al. [41] studied the one-step dinitration that yields N-(1-ethylpropyl)-3,4-dimethyl-2,6

New hydrogen-bonding organocatalysts: Chiral cyclophosphazanes and phosphorus amides as catalysts for asymmetric Michael additions

• Helge Klare,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2014, 10, 224–236, doi:10.3762/bjoc.10.18

• their respective proton-donor capacity is higher [33]. Contrary to a literature protocol [34] synthesizing the [(ArNH)2P(S)Cl] precursors from PSCl3 and various anilines resulted in the exclusive formation of the mono- and trisubstituted products. The findings match those reported by Cremlyn et al. [35

Studies on the interaction of isocyanides with imines: reaction scope and mechanistic variations

• Ouldouz Ghashghaei,
• Consiglia Annamaria Manna,
• Esther Vicente-García,
• Marc Revés and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2014, 10, 12–17, doi:10.3762/bjoc.10.3

• isocyanoacetate were not productive (Table 1, entries 13 and 14) [20]. Additionally, with respect to imines, the reaction works well for substrates generated from aromatic aldehydes and anilines displaying o-, m- and p-substituents (Table 1, entries 1–7). Moreover, in one case the 3-aminoindole 6 was detected (27

• -aminoamide 7 (34%) was the major component. The formation of amidoamides has been reported in the p-toluenesulfonic acid-catalyzed interaction of anilines, amines and isocyanides [8]. On the other hand, the reaction of the same imine with cyclohexyl isocyanide gave azetidine 3j (34%) in a selective manner

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• reaction, including natural product related or complex small molecules (Figure 18) [37]. 3.3.3 Ni-catalyzed perfluoroalkylation of Csp2–H bonds. Two early reports by Y.-Z. Huang et al. described Ni-catalyzed perfluoroalkylation of anilines, benzene, furan, thiophene and pyrrole using ω-chloroperfluoroalkyl

• iodides [109][110]. Notably, the reaction was rather selective: only ortho- or para-functionalized anilines were obtained (the ratio of which depended on the solvent), and 5-membered heterocycles all yielded the α-perfluoroalkylated products (Table 35). This selectivity differs from the one observed by N

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• approaches toward the synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives have been reported [29][30][31][32][33][34][35][36][37][38][39][40][41][42]: (a) Ru- and Au-catalyzed cascade reactions between 2-(1H-indol-1-yl)anilines and alkynes [34][42]. (b) AlCl3-catalyzed Pictet–Spengler reactions

• between 2-(1H-indol-1-yl)anilines and aromatic aldehydes [38]. (c) Pd-catalyzed regioselective C–H olefination/cyclization sequences from indole-substituted anilines and electron-deficient terminal alkenes [37]. However, these methods require expensive metal catalysts, long reaction time and produce only

Triol-promoted activation of C–F bonds: Amination of benzylic fluorides under highly concentrated conditions mediated by 1,1,1-tris(hydroxymethyl)propane

• Pier Alexandre Champagne,
• Alexandre Saint-Martin,
• Mélina Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2013, 9, 2451–2456, doi:10.3762/bjoc.9.283

• under highly concentrated conditions, where solvents cannot interfere with the interaction between the organofluorine compound and the triol. Various benzylic fluorides react with secondary amines or anilines to form benzylic amines in good yields. Keywords: C–F bond activation; highly concentrated

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• found to be optimal, lie within a narrow range of pKa values. The authors suggested that TFA protonates the enone 83, thus accelerating the addition of the α-amino radical to the enone (84). The Nishibayashi group reported that α-amino radicals generated from a different class of amines, anilines 87

• intermolecular addition of α-amino radicals to Michael acceptors (Scheme 25) [92]. Oxygen was found to act as a chemical switch to two competing reaction pathways from the same starting anilines. Irradiation of a degassed solution of aniline 99, 2-benzylidenemalononitrile 100, 5 mol % Ir(ppy)2(bpy)](PF6) in MeCN

• Michael acceptors. Conjugated addition of α-amino radicals to Michael acceptors assisted by a Brønsted acid. Conjugated addition of α-amino radicals derived from anilines to Michael acceptors. Oxygen switch between two pathways involving α-amino radicals. Interception of α-amino radicals by

The first example of the Fischer–Hepp type rearrangement in pyrimidines

• Inga Cikotiene,
• Mantas Jonusis and
• Virginija Jakubkiene

Beilstein J. Org. Chem. 2013, 9, 1819–1825, doi:10.3762/bjoc.9.212

• Fischer–Hepp rearrangement takes place when N-nitroso secondary anilines are treated with HCl or HBr, other acids give poor results or none at all. To the best of our knowledge, there are no examples of the migration of a nitroso group in heterocyclic compounds in the scientific literature. Obviously, the

Zinc–gold cooperative catalysis for the direct alkynylation of benzofurans

• Yifan Li and
• Jérôme Waser

Beilstein J. Org. Chem. 2013, 9, 1763–1767, doi:10.3762/bjoc.9.204

• knowledge, the direct alkynylation of benzofurans is still an unknown process. Since 2009, our group has developed a mild gold-catalyzed [14][15][16][17] method for the alkynylation of electron-rich aryls such as indoles and pyrroles [18], thiophenes [19], anilines [20] and furans [21]. Key for success was

Computational study of the rate constants and free energies of intramolecular radical addition to substituted anilines

• Andreas Gansäuer,
• Meriam Seddiqzai,
• Tobias Dahmen,
• Rebecca Sure and
• Stefan Grimme

Beilstein J. Org. Chem. 2013, 9, 1620–1629, doi:10.3762/bjoc.9.185

• ][7][8] proceeding via catalysis in single electron steps (for experimental results see Scheme 1) [9][10]. The C–C bond forming step of the catalytic cycle is an intramolecular alkyl radical addition to substituted anilines. Even though only rarely used, reaction sequences employing such steps in an

• substituted anilines that constitutes the C–C bond forming event of indoline synthesis via homolytic substitution with computational methods. The results are of general interest for the understanding of radical addition to electron rich arenes and should be helpful in the design of novel radical reactions

• , this approach was employed in the investigations of the following intramolecular radical additions to arenes. Investigation of the radical addition to substituted anilines In our preparative work, we have been mostly concerned with the catalytic synthesis of indolines via addition reactions of epoxide

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• biosynthetic precursor) to the culture medium, furnishing 40 mg of 4 from 120 L [3]. Aurachin D analogues with variations of the aromatic cycles The same methodology was tentatively applied to other anilines such as 2-naphthylamine (12), p-anisidine (13), 3,4-(methylenedioxy)aniline (14), 3,4-difluoroaniline

• (15) and methyl 3-aminobenzoate (16), using the 2-farnesyl(acetoacetate) 8a. Not surprisingly, only the electron-rich anilines 12–14 were reactive enough to furnish the expected 3-farnesyl-4(1H)-quinolones 17–19 in moderate to good yields (Table 1). The electron-poor anilines 15 and 16 were unreactive

An organocatalytic route to 2-heteroarylmethylene decorated N-arylpyrroles

• Alexandre Jean,
• Jérôme Blanchet,
• Jacques Rouden,
• Jacques Maddaluno and
• Michaël De Paolis

Beilstein J. Org. Chem. 2013, 9, 1480–1486, doi:10.3762/bjoc.9.168

• high yield (91%). The Mannich coupling was next attempted with different imines 2b–e in order to modulate the nature of the aryl moiety (Scheme 4). The electronic nature of the aniline being crucial for the stability of the imine and the hydroamination step, electronically rich anilines were selected

• to form imines 2b,c. Hence, when imines 2b,c were exposed to aldehyde 1a in the presence of catalyst 6 (available in racemic form), the Mannich adducts 7i,j were obtained and directly reacted with phosphonium salt 3. In line with our procedure, the resulting acyclic anilines 8i,j were then exposed to

• TFA to promote the cyclization into pyrrolidines 4i,j which upon treatment with DBU were converted into pyrroles 5i,j in 41% and 52% overall yields. While p-alkoxy substituted (R = OAllyl, OBn) anilines are compatible, the methodology proved troublesome with o-alkoxy substituted anilines, the main

Isolation and X-ray characterization of palladium–N complexes in the guanylation of aromatic amines. Mechanistic implications

• Abdessamad Grirrane,
• Hermenegildo Garcia and
• Eleuterio Álvarez

Beilstein J. Org. Chem. 2013, 9, 1455–1462, doi:10.3762/bjoc.9.165

• Vespucio 49, 41092 Sevilla, Spain 10.3762/bjoc.9.165 Abstract In the context of palladium-catalyzed guanylation of anilines herein, we have been able to characterize and isolate bis(anilino) and bis(guanidino)Pd(II) complexes using reaction conditions under which stoichiometric amounts of palladium salts

• are used. Characterization of these palladium complexes strongly supports a mechanistic proposal for the catalytic guanylation of anilines using PdCl2(NCCH3)2 as catalyst that involves the intermediacy of these Pd(II) complexes. Keywords: coordination chemistry; guanylation reaction; homogeneous

• the present report we describe the study of palladium-catalyzed guanylation of three additional anilines (1a–c) with N,N’-diisopropylcarbodiimide (2). For these reactions we have been able to characterize three palladium complexes of the type of bis(anilino)Pd(II) (3a–c) as well as three palladium

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst

• Cybille Rossy,
• Eric Fouquet and
• François-Xavier Felpin

Beilstein J. Org. Chem. 2013, 9, 1426–1431, doi:10.3762/bjoc.9.160

• ) with variously N-protected-2-iodoanilines gave contrasted results. Indeed, excellent yields of the corresponding indoles were obtained with anilines bearing mesyl, tosyl or Boc protecting groups (compounds 3–5), while only an uncyclized product was obtained with acetate (compound 7). The free indole

• acceptable yields. The Sonogashira alkynylation–cyclization sequence was successfully applied to a variety of alkynes and iodo-anilines (Scheme 5). As a general comment, aromatic alkynes consistently furnished a high yield of the corresponding indoles whatever the nature of the electrophile (compounds 4, 21

• with aryl acetylenes suggesting a strong halide effect and a sensitivity of the Pd–X bond under our reaction conditions. Indeed, the coupling of aryl acetylenes with bromo-anilines and bromo-phenols showed lower conversion compared to the iodo-congeners. We further evaluated the potential of our Pd–Cu

Palladium-catalyzed synthesis of N-arylated carbazoles using anilines and cyclic diaryliodonium salts

• Stefan Riedmüller and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2013, 9, 1202–1209, doi:10.3762/bjoc.9.136

• The direct synthesis of N-arylated carbazoles through a palladium-catalyzed amination of cyclic iodonium salts with anilines is described. In particular, electron-poor aniline derivatives reacted smoothly with only 5 mol % of Pd(OAc)2 as catalyst to give the desired products in up to 71% yield

• present an alternative Pd-catalyzed method for the construction of N-substituted carbazoles based on a stable, cyclic iodonium salt and electron-deficient anilines [24][25]. In the initial C–N bond-forming step of this cascade reaction, a ring opening of the cyclic iodonium salt through the amine is

• isolated yield. After we had gained a better understanding about byproduct formation, we decided to explore various substituted anilines under our optimized reaction conditions (Figure 3). Electron-rich p-toluidine (2b) gave the corresponding carbazole 3b in only 45% yield. Comparable results were obtained

An aniline dication-like transition state in the Bamberger rearrangement

• Shinichi Yamabe,
• Guixiang Zeng,
• Wei Guan and
• Shigeyoshi Sakaki

Beilstein J. Org. Chem. 2013, 9, 1073–1082, doi:10.3762/bjoc.9.119

• ) geometries were obtained and are shown in Figure 7. Their activation energies were calculated to be +28.52 kca/mol and +29.57 kcal/mol relative to the energy of Int1(V), respectively. These similar values indicate that both 2- and 4-Cl-substituted anilines may be formed almost equally according to the normal

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• acid (4) was reacted with substituted anilines 5 under standard EDC-mediated amidation conditions, followed by TFA-catalyzed deprotection to afford amides 6. A subsequent second amidation with benzoic acids 7 afforded final bis(amide) analogues 8. We also synthesized a model azide (Scheme 2). Synthesis

Synthesis of functionalized spiro[indoline-3,4’-pyridines] and spiro[indoline-3,4’-pyridinones] via one-pot four-component reactions

• Li-Juan Zhang,
• Qun Wu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2013, 9, 846–851, doi:10.3762/bjoc.9.97

• separation process, only the main product was separated from the reaction mixtures by column chromatography. The other product was not separated or structurally characterized. The results are listed in Table 2. It is interesting to find that anilines bearing p-chloro, m-chloro or p-bromo groups afforded

• -methylaniline and aniline itself gave spiro[indoline-3,4’-pyridinones] 3a–3j as the main products (Table 2, entries 9–18). Thus, it seems that anilines with electron-withdrawing groups preferably give spiro[indoline-3,4’-pyridines] 2, while anilines with electron-donating groups preferably produce spiro

• attacked the ester group to give spiro[indoline-3,4’-pyridinones] 3 with the elimination of ethanol. In this reaction process, the reasons that anilines with electron-withdrawing groups preferably attack the cyano group and anilines with electron-donating groups preferably attack the ester group are not

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• a benzofuran or an indole core. Our first study involved the cyclization of allyl moieties such as allyl ether 1a or N-allyl protected anilines 1b–c, easily prepared by quantitative allylation of o-iodophenol and o-iodoanilines using allyl bromide in DMF (Scheme 1). Following the protocol optimized

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• Hasi Rani Barai Hai Whang Lee Department of Chemistry, Inha University, Incheon 402-751, Korea 10.3762/bjoc.9.68 Abstract Kinetic studies on the reactions of Y-aryl phenyl isothiocyanophosphates with substituted X-anilines and deuterated X-anilines were carried out in acetonitrile at 55.0 °C. The

• free-energy relationships with X in the nucleophiles were biphasic concave upwards with a break region between X = H and 4-Cl, giving unusual positive ρX and negative βX values with less basic anilines (X = 4-Cl and 3-Cl). A stepwise mechanism with rate-limiting bond breaking for more basic anilines

• and with rate-limiting bond formation for less basic anilines is proposed based on the positive and negative ρXY values, respectively. The deuterium kinetic isotope effects involving deuterated anilines (XC6H4ND2) showed primary normal and secondary inverse DKIEs for more basic and less basic anilines

A one-pot catalyst-free synthesis of functionalized pyrrolo[1,2-a]quinoxaline derivatives from benzene-1,2-diamine, acetylenedicarboxylates and ethyl bromopyruvate

• Mohammad Piltan,
• Loghman Moradi,
• Golaleh Abasi and
• Seyed Amir Zarei

Beilstein J. Org. Chem. 2013, 9, 510–515, doi:10.3762/bjoc.9.55

• )anilines with alkynes to form 4,5-dihydropyrrolo[1,2-a]quinoxalines [23][24]. Kobayashi and co-workers have described the Lewis acid catalyzed cyclization of 1-(2-isocyanophenyl)pyrroles to give pyrrolo[1,2-a]quinoxalines in good yields; however, the isocyanide substrates required multistep synthesis [25