Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• proposed a catalytic mechanism and later reported a tin free aryl–amine coupling reaction [6][7]. This major breakthrough made the C–N coupling reaction accessible to a wide range of substrates, including anilines, which did not react very well with the previous conditions. However, despite the

• active compounds [11][12]. In 2009 the groups of Stevens and van der Eycken reported on the Chan–Lam reaction as a continuous flow protocol using copper(II) acetate (1.0 equiv), pyridine (2.0 equiv) and triethylamine (1.0 equiv) in dichloromethane [13]. Generally, when using anilines or phenols as the

• prepared to demonstrate the scope of the reaction conditions. Excellent isolated yields were obtained when anilines were used as the nucleophilic partner with both 4-methoxyphenylboronic acid (90% yield of 21) and phenylboronic acid (92% yield of 22) as the aryl donors (Scheme 2). Phenylboronic acid also

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• an FeCl3-catalyzed Kabachnik–Fields reaction of 2-alkynylbenzaldehydes 72, anilines 73, and phosphonates followed by a PdCl2-catalyzed 5-exo-dig cyclization (Scheme 18) [45]. The desired (2H-isoindol-1-yl)phosphonates 74 were obtained under optimized conditions (5 mol % of FeCl3, 5 mol % of PdCl2

• -phosphonates: A one-pot three-component synthesis of N-arylisoquinolone-1-phosphonates 119 through the Kabachnik–Fields reaction of ethyl 2-(2-formyl-4,5-dimethoxyphenyl)acetate (116) with anilines 117 and triethyl phosphite in the presence of trifluoroacetic acid as catalyst has been reported by Borse et al

• -aryl-3-oxoisoindolin-1-yl)phosphonates. FeCl3 and PdCl2 co-catalyzed three-component reaction of 2-alkynylbenzaldehydes, anilines, and diethyl phosphonate. Three-component reaction of 6-methyl-3-formylchromone (75) with hydrazine derivatives or hydroxylamine in the presence of diethyl phosphonate

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• lower enantioselectivities for the addition of para-substituted anilines to α,β-unsaturated imines [41]. Gil and Collin have also reported on the same reaction as Sodeoka, but using a samarium-BINOL catalyst system, which proceeded with lower enantioselectivity [42]. Sodeoka found that minimizing the

(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

• excellent diastereoselectivities (1.2:1–57:1 dr). In 2011, Chen, Xiao and co-workers, based on their previous work [77], described the aza-Michael–Michael cascade between substituted anilines 178 and nitroolefin enoates 172, utilizing a bifunctional cinchonine-derived thiourea 57 (Scheme 58) [79]. The

• reaction proceeds very smoothly for a variety of substrates affording the desired products in excellent yields and selectivities. In 2012, Xu and co-workers described an alternative route to highly-functionalized tetrahydroquinolines employing a domino aza-Michael–Michael reaction of substituted anilines

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• anilines resulting in the formation of 2-aryl-α-ketoacetamides was reported by Jiao [22] and a closely related intramolecular variant leading to isatins has been published by Ilangovan [23]. A remarkable Cu-catalyzed chemoselective oxidative C–C bond cleavage of methyl ketones was reported by the group of

Enantioselective additions of copper acetylides to cyclic iminium and oxocarbenium ions

• Jixin Liu,
• Srimoyee Dasgupta and
• Mary P. Watson

Beilstein J. Org. Chem. 2015, 11, 2696–2706, doi:10.3762/bjoc.11.290

• imine substrates. In 2002, Li and co-workers reported enantioselective alkynylations of N-aryl aldimines formed in situ from benzaldehydes and anilines (Scheme 1) [16][17]. This reaction employs a CuOTf/Ph-Pybox catalyst system to achieve generally high yields and ee’s of propargylic amines 2. Notably

Half-sandwich nickel(II) complexes bearing 1,3-di(cycloalkyl)imidazol-2-ylidene ligands

• Johnathon Yau,
• Kaarel E. Hunt,
• Laura McDougall,
• Alan R. Kennedy and
• David J. Nelson

Beilstein J. Org. Chem. 2015, 11, 2171–2178, doi:10.3762/bjoc.11.235

• ) and [NiCl(Cp)(IPr*OMe)] (7) due to their demonstrated competence as catalysts for the arylation of anilines [11]. The results from the cross-coupling reactions with 4’-bromo- and 4’-chloroacetophenone are summarised in Table 3; running the latter reaction for more than 2 h did not lead to significant

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• electron-enriched arenes [7][8][9], diazotization/halogenations of anilines [10], and ortho-lithiation/halogenations sequence [11] among others are widely used as traditional strategies for creating C–X bonds. However, one or more problems such as poor site-selectivity, reliance on toxic halogen sources

• ] devised a practical copper-catalyzed halogenation of anilines 8 containing an easily removable N-(2-pyridyl)sulfonyl auxiliary. In the presence of copper(II) halide catalyst and NXS (X = Cl or Br), a class of o-chloro/bromoanilines 9 were efficiently provided under aerobic atmosphere (Scheme 6). The N-(2

• via oxidation by Cu(II) and release of Cu(I). The presence of molecular oxygen regenerated the Cu(I) species to the Cu(II) catalyst via re-oxidation. In their subsequent study, Gusevskaya et al. found that anilines were also able to be halogenated via a similar operation. However, the products were

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• their syntheses require additional steps because the necessary anilines – the starting materials for the preparation of NHCs precursors – are not commercially available [10][11]. Up until now, there had been no disclosures of increased catalyst efficiency caused by the exchange of chlorides with larger

Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

• Hanmo Zhang,
• E. Ben Hay,
• Stephen J. Geib and
• Dennis P. Curran

Beilstein J. Org. Chem. 2015, 11, 1649–1655, doi:10.3762/bjoc.11.181

• /fragmentation. Tin hydride-mediated cyclizations of 2-halo-N-(3-methyl-N-sulfonylindole)anilines provide spiro[indoline-3,3'-indolones] or spiro-3,3'-biindolines (derived from imine reduction), depending on the indole C2 substituent. Cyclizations of 2-haloanilide derivatives of 3-carboxy-N-sulfonyl-2,3

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• access to SF5-phenylboronates appears to be starting from readily available SF5-substituted anilines or diazonium salts rather than SF5-containing halobenzenes. Herein, we report a new protocol for efficient borylation, iodination and hydrodediazoniation of SF5-phenyldiazonium tetrafluoroborates in the

• presence of pyridine. The generality of the borylation and iodination reactions was demonstrated on several examples. Results and Discussion At the onset of our investigation, Sandmeyer-type borylation of 3- and 4-(pentafluorosulfanyl)anilines (1a and 1b, respectively) to pinacolboronates 2a and 2b

• potassium SF5-phenyltrifluoroborates were found to be highly reactive with a variety of aryl bromides and iodides in the presence of catalytic amounts of PdCl2(dppf)·CH2Cl2 or Pd(OAc)2 [72]. The recently published synthesis of arylboronic acids from anilines or aryldiazonium tetrafluoroborates using B2(OH)4

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• enzyme affinity. Results and Discussion Azobenzenes can be synthesized by a variety of known chemical transformations [8]. Among them the most widely used is the diazotization of aniline, followed by trapping of the diazonium salt with an electron-rich aromatic compound (such as anilines and phenols

• ). Another commonly used method is the condensation between anilines and aryl nitroso compounds, known as the Mills reaction. According to these transformations, nine sulfonamide containing azobenzenes 1a–i with different moieties in the 4´-position were synthesized. The substitution in the 4´-position will

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

• . Anilines having halogen substituents at various positions of the aromatic ring furnished the corresponding succinimides in high yields (Table 2, entries 6–9). We were expecting some interference by the iodine in the ortho-position due to a probable formation of a radical; however, we did not observe such

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• work for electron-deficient anilines. Despite this limitation, Hii and co-workers expanded the methodology to other α,β-unsaturated N-alkenoylbenzamides [238] and carbamates [239][240] (Scheme 32). In order to find means to overcome the low enantioselectivities observed when electron-rich anilines are

• difference in observed enantioselectivity of the aza-Michael addition using the previous protocol and the slow addition protocol. In the report by Sodeoka and co-workers, the authors took a different approach to increasing the enantioselectivity of the 1,4-addition of electron-rich anilines [242]. To

• enantioselectivities when both electron-deficient and -rich anilines were added (Scheme 34). In 2008, Collin and co-workers developed the asymmetric aza-Michael addition of N-alkenoyloxazolidinones catalyzed by iodo(binaphtholato)samarium [243]. This group had previously reported the use of samarium diiodide in the

3-Glucosylated 5-amino-1,2,4-oxadiazoles: synthesis and evaluation as glycogen phosphorylase inhibitors

• Marion Donnier-Maréchal,
• David Goyard,
• Vincent Folliard,
• Tibor Docsa,
• Pal Gergely,
• Jean-Pierre Praly and
• Sébastien Vidal

Beilstein J. Org. Chem. 2015, 11, 499–503, doi:10.3762/bjoc.11.56

• with the N,N’-ditolylcarbodiimide, although the starting material was consumed. The mechanism proposed by Ispikoudi et al. [33] proposes the amine moiety as a leaving group during this process. Anilines (R = tolyl) are worse leaving groups than alkylamines (R = iPr, C6H11), thus providing a likely

Matsuda–Heck reaction with arenediazonium tosylates in water

• Ksenia V. Kutonova,
• Marina E. Trusova,
• Andrey V. Stankevich,
• Pavel S. Postnikov and
• Victor D. Filimonov

Beilstein J. Org. Chem. 2015, 11, 358–362, doi:10.3762/bjoc.11.41

• from commercially available anilines than from haloarenes or triflates. Typically, alcohols, THF or DMF are used as solvents for Matsuda–Heck reactions. One of the most rapidly developing trends in organic synthesis is the carrying out of reactions in water following a «Green chemistry» approach [4

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

Multicomponent versus domino reactions: One-pot free-radical synthesis of β-amino-ethers and β-amino-alcohols

• Bianca Rossi,
• Nadia Pastori,
• Simona Prosperini and
• Carlo Punta

Beilstein J. Org. Chem. 2015, 11, 66–73, doi:10.3762/bjoc.11.10

• situ afforded the desired products 1a–1g in good yields, both starting from different acyclic and cyclic ketones (Table 2, entries 1–5) and from different amines (Table 2, entry 6 and entry 7). As already observed in our previous reports, secondary anilines were not converted under our operative

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• used readily available N-(o-halobenzyl)arylamines as starting materials [17]. The o-haloarylbenzylamines (obtained by nucleophilic substitution of various anilines with 2-iodobenzyl chloride) gave the corresponding amide anions by an SRN1 substitution reaction in NH3 or DMSO as solvent under

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• with different substituents on the aromatic ring and on the alkynyl group were cyclized in good to excellent yields. When N-ethoxycarbonyl-substituted anilines are converted under the conditions described above, the carbamate group is cleaved and unprotected indoles are obtained. An electrochemical

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• Clausthal-Zellerfeld, Germany 10.3762/bjoc.10.170 Abstract The reaction of mercaptoacetic acid esters with pentachloro-2-nitro-1,3-butadiene (1) provides an appropriate precursor for the synthesis of special thiazolidin-4-ones. Applying different anilines as the second constituent for the requisite

• -substituted anilines 16–18 two atropisomers were generated. This phenomenon is due to a less hindered rotation of the C–N bond of the former anilines (Figure 1). The steric hindrance is additionally forcing by the s-cis conformation of the nitrobutadiene moiety (cf. Figure 2). A DFT calculation of the energy

• addition to the anilines described above (Scheme 2), we applied 1-naphthylamine as a bulkier aromatic representative and morpholine as a secondary, more basic aliphatic amine. Conversion of 3 and 5 with morpholine and 1-naphthylamine afforded the open chain products 20 and 21 in 93% and 80% yield

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• base and benzyltriethylammonium bromide acted as a phase-transfer agent. This procedure was applied to the synthesis of N-arylphosphoramidate. It was observed that the classical AT reaction (CCl4, base, anhydrous solvent) applied to ortho-substituted anilines was not successful. However, the use of

On the mechanism of photocatalytic reactions with eosin Y

• Michal Majek,
• Fabiana Filace and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2014, 10, 981–989, doi:10.3762/bjoc.10.97

• , arenediazonium salts are especially attractive precursors which constitute versatile alternatives to haloarene-based strategies. They are readily available by diazotization of anilines, no toxic metals are required; the bond cleavage generates gaseous N2 which escapes the reaction mixture. Photoredox reactions

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• . Continued studies in our group will focus on further expanding the scope of the [3 + 2] annulation to include substituted anilines and other types of π-bonds. Experimental General procedure for the [3 + 2] annulation of cyclopropylanilines with alkynes: an oven-dried test tube (16 × 125 mm) equipped with a

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• ethers [14] and enolic 1,3-diketo compounds [15], have been reported to react with N-acyliminium ions obtained either from 2-formylbenzoic acid and anilines [11][12] or from N-acyliminium ions prepared from N-arylphthalimides [13][14][15]. Nucleophilic substitution of N-aryl-3-hydroxyisoindolinones from

• analogous to the final step of imino [4 + 2] Diels–Alder reactions between N-acyliminium ions and electron-rich dienophiles are reported [13][14][15]. We synthesized eight N-aryl-3-hydroxyisoindolinones from substituted anilines and phthalic anhydride following the reported procedure [13]. Previously

• donating groups at the para position of the aniline generally led to the formation of products in higher yields in comparison to those bearing electron withdrawing groups (e.g., R2 = –Cl, –F). Similar observations were made previously [13]. Furthermore, in the case of anilines with meta substitution, the