Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• cyclic diaryl-λ3-iodanes (Scheme 26) [66]. The palladium phosphine ligand plays a crucial role as a bidentate ligand with a bite angle greater than 100° such as DPEphos (104°) or Xantphos (108°) significantly improves the yields. The reaction applies to a series of anilines and aliphatic amines, but

• electron-poor anilines afford better results than their electron-rich congeners, while a hindered amine (t-BuNH2) completely inhibits the reaction. Shortly after, a similar synthesis of carbazoles involving Cu(OAc)2 as the catalyst in the presence of ethylene glycol both as a ligand and the co-solvent has

• been reported (Scheme 27) [67]. A variety of amines such as anilines, sulfonamides and aliphatic amines has been utilized though in large excess. But in contrast to the previous method, electron-rich anilines proved to be better candidates for this reaction than the electron-poor analogs. The group of

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• recently, Bolm and co-workers reported a metal-free cyclization of iodo-substituted diaryl ethers with a broad scope (Scheme 1b) [18]. Transition metal-catalyzed cross couplings have also been employed to form the required C–O and C–N bonds, e.g., by Cu-catalyzed cyclization of 2-(2-bromophenoxy)anilines

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

• for iodane-mediated double functionalisations with aryl iodonium salts. Another achievement of Greaney and co-workers is the atom-economical double arylation of anilines 16 with symmetrical diaryliodonium salts 1 (Scheme 9) [34]. The corresponding triarylamines 17 are important structural motifs for

• arylation. Unfortunately, a selective aryl transfer using unsymmetrical diaryliodonium salts was not successful under the reaction conditions, giving only mixtures of mono N-arylated anilines in low yields after the first step. A different approach towards the functionalisation of heterocycles was taken by

• triarylamines 17 through a double arylation of anilines. Selective conversion of novel aryl(imidazolyl)iodonium salts 1b to 1,5-disubstituted imidazoles 18. Selected examples for the application of cyclic diaryliodonium salts 19. Tandem oxidation–arylation sequence with (dicarboxyiodo)benzenes 20. Oxidative α

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• )iodonium salts [12][13][14] and describe here the development of a C–N coupling of a phthalimide anion with non-sterically biased aryl groups. The protocol is compatible with ortho-, meta-, and para-substitution on the aryl group and the phthalimide moiety may also provide access to anilines. Results and

• as an important scaffold. Scope of compatible aryl groups. Conditions: 1 (0.5 mmol, 1 equiv), potassium phthalimide (2.5 mmol, 5 equiv), toluene (2.5 mL), 100 °C, 24 hours. Isolated yields are reported. One-pot synthesis of anilines. Discovery and optimization of reaction conditions.a Comparison of

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• application of a Pd-catalyzed Buchwald–Hartwig amination. In recent years, extensive efforts have been made on the Pd(0)-catalyzed amination of aryl halides or triflates in order to achieve the efficient synthesis of substituted anilines [6][7][8][9]. Buchwald et al. stated that the Pd source is determining

• -bromo-13α-estrone 3-methyl (1 or 3) as well as 3-benzyl ethers (2 or 4) with aniline or substituted anilines as reagents. To the best of our knowledge, there are no literature reports concerning the Pd-catalyzed 2- or 4-amination of the estrane core. Results and Discussion Based on recent literature

• the presence of X-Phos or BINAP as ligands. The literature data influenced the selection of the base. The arylation of anilines, escpecially of unsubstituted ones with o-bromoanisoles requires stronger bases such as NaOt-Bu or KOt-Bu [34][35][36][37][38]. This is due to the deactivated, electron-rich

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• ]. With thiocarbonates 4 and 6 in our hands, their electrochemical behavior was studied in the MeOH/H2O media previously described (Figure 1). This mixture of solvents has been used for the electrochemical preparation of anilines, hydroxylamines and nitroso compounds via the reduction of aromatic nitro

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• target functional groups. Recently, several examples of conversion of anilines into trifluoromethylated arenes, named Sandmeyer type trifluoromethylation, were disclosed. This protocol offered a complementary method for the synthesis of trifluoromethylated arenes from the corresponding aromatic amines

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• al. we achieved compound 43 in a yield of 77% over two steps [54]. This material was functionalized in two different studies: first by using pyridine-type anilines and later with R-group modifications to the top ring (Scheme 9) [55][56]. Among the quadracyclic adenine analogues in those two studies

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• be increased. To overcome this limitation, anilines were used as redox mediators, which are first oxidized by the photocatalyst and subsequently activate the aliphatic thiol via direct hydrogen abstraction or sequential electron- and proton-transfer steps. With this concept they were now able to

• efficiently couple a series of functionalized aryls with the thiol moiety of cysteine, applying the organic photocatalyst Eosin Y. The respective aryl diazonium salts were generated in situ from the respective anilines, tert-butyl nitride and catalytic amounts of p-toluenesulfonic acid. Also in 2017, Fu and

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

• synthesis of modified nucleosides, in particular 8-CF3-2’-deoxyguanosine and 8-CF3-inosine in 39 and 73% yields, respectively [58]. The same copper-free method was applied for the trifluoromethylation of a variety of electron-deficient 4-substituted acetanilides or anilines (Scheme 36). In these reaction

• conditions, Cao’s group reported that acetanilides or anilines featuring electron-donating substituents at the para-position of the acetamino group afforded mixtures of isomeric C−H trifluoromethylation products in moderate yields. However, with substrates bearing electron-withdrawing groups, ortho-CF3

• acetanilides or anilines were obtained as sole products [59]. To meet high expectations of environmentally low impact chemical reactions, Lipshutz and co-workers carried out the trifluoromethylation of heterocycles using aqueous micellar conditions based on the surfactant TPGS−750−M in water at room

Development of a fluorogenic small substrate for dipeptidyl peptidase-4

• Futa Ogawa,
• Masanori Takeda,
• Kanae Miyanaga,
• Keita Tani,
• Ryuji Yamazawa,
• Kiyoshi Ito,
• Atsushi Tarui,
• Kazuyuki Sato and
• Masaaki Omote

Beilstein J. Org. Chem. 2017, 13, 2690–2697, doi:10.3762/bjoc.13.267

• groups. The data in Table 1 show that Hiyama cross-coupling reactions gave the desired TFPE-anilines and TFPE-phenylenediamines (1–4) in moderate to good yields. This method has the advantage that complete substitution of diiodo- and triiodoarenes can proceed to give disubstituted (1 and 3) and

• solution. TFPE-anilines 1 and 2 gave moderate fluorescence quantum yields of 0.31 and 0.30, respectively. In comparison with these, the fluorescence quantum yields of TFPE-phenylenediamine 3 was slightly lower, namely 0.25. The introduction of one more TFPE group into 3, to give 4, further decreased the

• on addition of DPP-4. Use of 1 as fluorogenic probe for DPP-4 activity. Synthesis of fluorogenic probe H-Gly-Pro-1. Synthesis of TFPE-anilines 1–4 via Hiyama cross-coupling reactions of iodoanilines with (E)-trimethyl(3,3,3-trifluoroprop-1-enyl)silane.a UV–vis absorption and fluorescence data for 1–4

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• consecutive transformations. For instance, para-substituted halogenated anilines 3 (Table 5, entries 3–5) and ethyl 4-aminobenzoate (Table 5, entry 6) furnish the desired products in 51–65% yield. Interestingly, also sterically hindered anilines, such as 2,6-dimethylaniline can be obtained in 56% yield (Table

Dialkyl dicyanofumarates and dicyanomaleates as versatile building blocks for synthetic organic chemistry and mechanistic studies

• Grzegorz Mlostoń and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 2235–2251, doi:10.3762/bjoc.13.221

• 51 [56] (Scheme 17). Further reaction with excess NH3 gives rise to the corresponding monoamide 52. Analogous reactions with differently substituted anilines and β-naphthylamine, respectively, afforded the corresponding enamines of type 51, when the amine was used in excess. On the other hand, the

• observation was made when less nucleophilic anilines were used as trapping agents. The formation of adducts of type 56 proceeds in competition with the trapping reaction by a second molecule of 55 leading to the homologue enamine 59 [60]. Finally, reactions performed with 55 in the absence of any trapping

Solvent-free and room temperature synthesis of 3-arylquinolines from different anilines and styrene oxide in the presence of Al₂O₃/MeSO₃H

• Hashem Sharghi,
• Mahdi Aberi,
• Mohsen Khataminejad and
• Pezhman Shiri

Beilstein J. Org. Chem. 2017, 13, 1977–1981, doi:10.3762/bjoc.13.193

• been developed in the presence of Al2O3/MeSO3H via one-pot reaction of anilines and styrene oxide. This methodology provides very rapid access to 3-arylquinolines in good to excellent yields under solvent-free conditions at room temperature in air. Keywords: 3-arylquinolines; Al2O3; MeSO3H; one-pot

• anilines with styrene oxide via C–C cleavage is the efficient synthetic route to quinolones [1]. The reaction was performed using FeCl3 as catalyst in 1,4-dioxane as solvent at 110 °C for 12 h. According to the significance of this progress, we have decided to re-optimize it. The mixture of Al2O3 and

• using a mixture of Al2O3 (0.1 g) and MeSO3H (0.3 mL) under solvent-free conditions at room temperature for 10 min (Table 1, entry 6). Various anilines with electron-withdrawing and electron-donating functional groups such as o-Me, m-Me, p-Me, m-Et, p-MeO, m-Br, o-Cl, 3,4-dimethyl and p-OEt were treated

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• efficiently used for the preparation of ortho-functionalized anilines. This contribution deals with a new access to ring-annelated sultams by an intramolecular Pd(0)-catalyzed arylation of tertiary sulfonamides bearing an additional C–H acidic center (Scheme 1). From several potentially suitable electron

• problem in the alkylation of the sulfonamide 3a, the sequence of steps was reversed. Thus, 2-iodo-N-(4-methoxybenzyl)anilines 7a–g were prepared by reduction of the Schiff bases obtained from 2-iodoanilines 1a–g and 4-methoxybenzaldehyde with sodium cyanoborohydride in a mixture of glacial acetic acid and

• , methyl 2-[N-(2-iodo-4-methylphenyl)-N-(4-methoxybenzyl)sulfamoyl]acetate (8b) and methyl 2-[N-(4-chloro-2-iodophenyl)-N-(4-methoxybenzyl)sulfamoyl]acetate (8c) could be prepared in 52 and 62% yield, respectively (Scheme 3). In a recent paper Xu et al. report sulfonylation of sluggish anilines with

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• ][75][76]. In view of this, chemists have introduced alternative energy sources like, microwave, sonication, mechanomilling, etc. [12][27][77]. Su and co-workers reported a copper-catalyzed arylation of anilines using arylboronic acid under high speed ball-milling conditions. Using 1.0 equiv of Cu(OAc

• )2 and 2.5 equiv of K2CO3 and in the presence of milling auxiliary silica gel, differently substituted arylboronic acid and anilines led to N-arylated products in 58–86% yield (Scheme 15) [78]. They have also explored the reactivity of other amines like alkyl, primary, secondary, heterocyclic, etc

• anilines proceed through the formation of unisolable reactive intermediate, aryl N-thiocarbamoylbenzotriazole, which rapidly decomposes to the corresponding isothiocyanate in organic solvent [189]. The Štrukil and Friščić group successfully demonstrated the formation of aryl-N-thiocarbamoylbenzotriazole

Mechanochemical synthesis of thioureas, ureas and guanidines

• Vjekoslav Štrukil

Beilstein J. Org. Chem. 2017, 13, 1828–1849, doi:10.3762/bjoc.13.178

• were selected as gaseous amines and quantitatively afforded thioureas at pressures of 0.4–1 bar and reaction temperatures of −30 °C to rt , solid anilines such as 4-methoxy, 4-chloro and 4-bromoaniline were reacted in the solid-state under ball milling conditions at rt. In all three cases the authors

• -and-pestle synthesis of 14 diarylthioureas by reacting 4-ethoxy-, 4-chloro- and 4-bromophenyl isothiocyanates with several anilines. After manual grinding for 5–40 min, the crude products were recrystallized from ethanol or acetone, and dried under vacuum to afford the thioureas in 89–98% yield [31

• -withdrawing aryl isothiocyanates with anilines used for the synthesis of N,N'-disubstituted thioureas, thorough mixing in an agate mortar typically leads to the formation of the products in a couple of minutes. As an extension of the mechanochemical click-coupling of amines with isothiocyanates, the thiourea

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• , necessary for the synthesis of dihydroquinazolines 2, were prepared by N-alkylation of the arylamino group present in compounds 4 using alkyl halides. In a previous work [63], we developed a methodology for the selective N-alkylation of anilines with ω-halonitriles in the presence of cesium carbonate and

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• yielding the R-isomer at C25. This excellent facial selectivity has been demonstrated, e.g., for anilines as nucleophiles before. It is due to the preferred conformation around the bond at C24–C25 which leads to the efficient shielding of the si-face by the two germinal methyl groups at C22 [4][5]. The NMR

Chemoselective synthesis of diaryl disulfides via a visible light-mediated coupling of arenediazonium tetrafluoroborates and CS₂

• Jing Leng,
• Shi-Meng Wang and
• Hua-Li Qin

Beilstein J. Org. Chem. 2017, 13, 903–909, doi:10.3762/bjoc.13.91

• turns red upon exposure to sunlight due to decomposition and formation of radical species [20]. Subsequently, the photodecomposition of diazonium salts by loss of nitrogen upon exposure to light has been utilized in organic synthesis for example to remove amino groups from anilines [21] or for arylation

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• for the formation of aromatic mixed self-assembled monolayers containing both imine functionalities and protonated anilines on the surface [20]. In order to bring a new class of reusable surfaces, we describe herein the use of sulfamide chemistry for the generation of reversible patterns of sulfur

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• phenols in water at room temperature. This catalyst can be reused many times without loss of the catalytic activity. Moreover, this catalyst could also be applied in the synthesis of anilines. 1.1.2 Copper-catalyzed hydroxylation of aryl halides: Copper catalysts are considered as economical and stable

• noting that the developed protocol could be easily applied to the synthesis of anilines and aryl thiols. In 2014, the Jiang and Han group used a copper-doped graphitic carbon nitride catalyst Cu-g-C3N4, which was prepared from urea and CuNO3, and developed a ligand free protocol for the synthesis of

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• mixture of Ac2O and DMAP as reagents (Scheme 7). The MBH acetate 7 was further converted into the γ-aminophosphonates 8a–c within short reactions times of 1–2 h and in 60–81% isolated yields using anilines, and 1 equiv of cerium(III) chloride hexahydrate in refluxing toluene (Table 5, entries 1–3). The

Continuous-flow synthesis of primary amines: Metal-free reduction of aliphatic and aromatic nitro derivatives with trichlorosilane

• Riccardo Porta,
• Alessandra Puglisi,
• Giacomo Colombo,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2016, 12, 2614–2619, doi:10.3762/bjoc.12.257

• aromatic rings followed by reduction is the most classical entry for the preparation of anilines [1][2]. Lately, also aliphatic nitro derivatives have become more and more popular: a wide variety of highly functionalized and chiral aliphatic nitro compounds, precursors of the corresponding chiral amines

• conditions, but the presence of noble metal catalysts, packed into disposable cartridges, suffers from functional group compatibility and catalyst poisoning during time. In 2012 Kappe’s research group reported the microwave-assisted continuous-flow synthesis of anilines from nitroarenes using hydrazine as

• reducing agent and iron oxide nanocrystals as the catalyst [25]. This methodology ensured fast transformations (2 to 8 minutes) of a wide number of substrates and was extended to large scale preparation of pharmaceutically relevant anilines [26]. However, this procedure required harsh reaction conditions

Facile synthesis of indolo[3,2-a]carbazoles via Pd-catalyzed twofold oxidative cyclization

• Chao Yang,
• Kai Lin,
• Lan Huang,
• Wei-dong Pan and
• Sheng Liu

Beilstein J. Org. Chem. 2016, 12, 2490–2494, doi:10.3762/bjoc.12.243

• ). Further disconnection of compounds 2 provided two commercially available basic fragments: 2,4-dibromobenzoic acid and anilines. Bergman et al. have described a synthetic route to indolo[3,2-b]carbazole by adopting twofold oxidative biaryl coupling as a key step [13], and the method has been further

• dibromobenzoic acid with sulfuric acid in methanol) with an excess of anilines in the presence of cesium carbonate and catalytic quantities of Pd(OAc)2 and BINAP were processed smoothly. The desired methyl 2,4-dianilinobenzoates (2a–e) were obtained in good to excellent yield. In a parallel synthesis, using the

• Houpis protocol [15], Cu-catalyzed selective monoaminations of the 2,4-dibromobenzoic acid at the 2-position were achieved. After methyl esterification of ortho-aminated benzoic acids, substrates 4a and b were treated with other anilines under the previous Buchwald–Hartwig conditions to afford methyl 2,4