Annulation of 1H-pyrrole-2,3-diones by thioacetamide: an approach to 5-azaisatins

• Aleksandr I. Kobelev,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2019, 15, 364–370, doi:10.3762/bjoc.15.32

• heterocycles; thioamides; Introduction Omnipresent among natural compounds and drugs, the indole core is a privileged scaffold for library design and drug discovery [1]. Its dioxo derivative, isatin (1H-indole-2,3-dione), is an important building block for the construction of diverse indole-based compounds

Oxidative radical ring-opening/cyclization of cyclopropane derivatives

• Yu Liu,
• Qiao-Lin Wang,
• Zan Chen,
• Cong-Shan Zhou,
• Bi-Quan Xiong,
• Pan-Liang Zhang,
• Chang-An Yang and
• Quan Zhou

Beilstein J. Org. Chem. 2019, 15, 256–278, doi:10.3762/bjoc.15.23

• indole moiety to afford the target product 64 along with the regenerated Rh(III) catalyst. A silver-catalyzed intramolecular cascade amination/ring-opening/cyclization of a variety of substituted MCPs 69 was proposed by Fan and co-workers, which provided a simple and efficient way for the building of

• and vinyl azides 92 for the synthesis of azaheterocyles 93 (Scheme 20) [98]. This strategy could also be applied to the synthesis of the quaternary indole alkaloid and melinonine-E. Quinones play an important role in organic chemistry because of their unique structure. In 2013, Malayappasamy and co

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• diverse substitution patterns in the aldehyde component (Scheme 2). According to the literature [47][48][49][50][51][52], the introduction of an indole core into a chromene moiety is an appealing task, which prompted us to investigate the possibility to use this nucleophile in the discovered process. The

• previously optimized conditions worked nicely for the reaction of N-(cyanomethyl)pyridinium chloride, o-hydroxybenzaldehyde and indole, producing the desired compound 6a with good 77% yield (Scheme 3, footnote a). Unfortunately, the employment of N-methylindole resulted in the formation of the inseparable

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• work by Arisawa et al. [75], who reported a synthesis of indoles by RCM of sterically less encumbered enamides, we investigated the RCM of 20. Unfortunately, no conversion to the indole 22 could be observed under various conditions. Ring-closing metathesis of 19 was, in contrast, successful and

• attempted synthesis of indole 22. Synthesis of 8-allyl-7-hydroxycoumarins 8. Synthesis of oxepino- 11 and furanocoumarins 3 from a common precursor 9. Synthesis of acrylates 12. Optimization of RCM conditions and synthesis of annellated coumarins 13. Synthesis of pyran-2-one-annellated coumarins 15 via

Synthesis of indole–cycloalkyl[b]pyridine hybrids via a four-component six-step tandem process

• Muthumani Muthu,
• Rakkappan Vishnu Priya,
• Abdulrahman I. Almansour,
• Raju Suresh Kumar and
• Raju Ranjith Kumar

Beilstein J. Org. Chem. 2018, 14, 2907–2915, doi:10.3762/bjoc.14.269

• condensation–nucleophilic addition to carbonyl–Michael addition–N-cyclization–elimination–air oxidation sequence to afford structurally intriguing indole–cycloalkyl[b]pyridine-3-carbonitrile hybrid heterocycles in excellent yields. Keywords: cycloalkyl[b]pyridine-3-carbonitrile; cyclododecanone; 3-(1H-indol-3

• four-component reaction of cyclic/acyclic ketones, malononitrile, aromatic aldehyde and ammonium acetate affording 2-amino-3-cyanopyridine derivatives have been explored extensively [45][46][47][48][49][50][51][52][53][54][55]. However, syntheses of pyridine scaffolds bearing an indole side chain have

• received less attention. For instance, the multicomponent reactions of aldehydes, 3-(1H-indol-3-yl)-3-oxopropanenitriles and 5-aminopyrazol or naphthylamine afforded indole substituted fused pyridine derivatives [56]. 2-Indole substituted pyridine derivatives have also been prepared through AlCl3-induced C

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• -based design built on the indoloquinolizinone 35 (Figure 8), afforded the chimeric molecule indole 36 (Figure 8) as an inhibitor of the ZipA/FtsZ interaction with an improved, but still modest, IC50 of 192 μM. The antibacterial activity of all the target compounds was also evaluated against a panel of

• library of small molecules whose inhibition properties were measured by a fluorescence polarization competition assay [89]. Derivatization of the indole nitrogen atom of lead compound 36 (Figure 8) returned the interesting indole analogue 37 (Figure 8). The authors then confirmed that the compounds were

• . catarrhalis, and E. coli (imp). Unfortunately, the most active compound, indole 37, exhibited an IC50 = 296 μM and a dissociation constant of 105 μM which undoubtedly make it a too weak inhibitor. Excitingly, the results are consistent with the inhibition of the ZipA/FtsZ interaction measured by FP and

An overview on recent advances in the synthesis of sulfonated organic materials, sulfonated silica materials, and sulfonated carbon materials and their catalytic applications in chemical processes

• Hashem Sharghi,
• Pezhman Shiri and
• Mahdi Aberi

Beilstein J. Org. Chem. 2018, 14, 2745–2770, doi:10.3762/bjoc.14.253

• (57). Two peaks due to C=C and C=N were observed at 1680 and 1540 cm−1. The bands at the range of 1200–1000 cm−1 are due to SO2 asymmetric and symmetric vibrations. A variety of aryl or heterocyclic aldehydes 7, 38, and 58 were reacted with indole or 5-bromo-1H-indole (6a) to synthesize the desired

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• conformation of the PqsR-DNA binding domain, whereas the LBD is not affected extensively. Aryloxyacetindoles Spero Therapeutics further optimized M64 (42), firstly by changing the phenoxyphenylamide into a carbonyl-linked indole containing a hetarylether (43) [80]. Afterwards they varied the linkage of the

Synthesis of 3-aminocoumarin-N-benzylpyridinium conjugates with nanomolar inhibitory activity against acetylcholinesterase

• Nisachon Khunnawutmanotham,
• Cherdchai Laongthipparos,
• Patchreenart Saparpakorn,
• Nitirat Chimnoi and
• Supanna Techasakul

Beilstein J. Org. Chem. 2018, 14, 2545–2552, doi:10.3762/bjoc.14.231

• . Hybrid compounds such as huperzine A–tacrine hybrids [5], donepezil–tacrine hybrid related derivatives [6][7] and tacrine–indole hybrids [8] with dual-binding site properties exhibit potent AChE inhibition activities. In addition, coumarin compounds linked with various side chain moieties [9][10][11] as

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• diverse alkenyl triflates was also examined. As a result, the desired carboxylic acids 4a–k were obtained in good-to-high yields, as shown in Scheme 5. Notably, the ester and p-toluenesulfonate functionalities in 4c and 4d, respectively, were tolerated. An indole-functionalized substrate 3f was converted

• in good TON. Benzofuran (32h) and indole (32i) also gave the carboxylic acids, which were isolated as their methyl esters. Li and co-workers reported the Rh-catalyzed site-selective C(sp2)–H carboxylation reaction using 2-arylphenols as the substrates (Scheme 31) [62]. The desired reactions proceeded

Synthesis of indolo[1,2-c]quinazolines from 2-alkynylaniline derivatives through Pd-catalyzed indole formation/cyclization with N,N-dimethylformamide dimethyl acetal

• Antonio Arcadi,
• Sandro Cacchi,
• Giancarlo Fabrizi,
• Francesca Ghirga,
• Antonella Goggiamani,
• Antonia Iazzetti and
• Fabio Marinelli

Beilstein J. Org. Chem. 2018, 14, 2411–2417, doi:10.3762/bjoc.14.218

• related to hinckdentine A received increasing attention as a source of new and useful pharmaceuticals. One well-established approach is based on the elaboration of a preformed indole ring, for example through cyclocondensation of 2-(o-aminophenyl)indoles with 2-cyanobenzothiazoles [14], aldehydes [9] and

• -(o-aminophenyl)indole derivatives followed by further cyclization [19][20][21][22]. Our interest in this field led to the development of an original approach to 6-trifluoromethyl-12-aryl(vinyl)indolo[1,2-c]quinazolines 4 through sequential Pd-catalyzed reactions of bis(o-trifluoroacetamidophenyl

• )acetylene (1) with aryl or vinyl halides and triflates followed by cyclization reactions (Scheme 1) [19]. The reaction, which tolerates a variety of important functional groups, likely involves the formation of the indole intermediates 2 (through aminopalladation/reductive elimination) [20][21] followed by

Correction: Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2018, 14, 2394–2395, doi:10.3762/bjoc.14.215

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• . Indoles also efficiently participated in intra- and intermolecular hydroarylation reactions to access useful organic skeletons [70][71][72][73]. Thus, the reaction of indole bearing an aldimine and homoallyl group 29 in the presence of CoBr2, SIMes·HCl and Me3SiCH2MgCl gave dihydropyrroloindoles 30

• in the presence of CoCp*(CO)I2 and AgNTf2 (Scheme 38) [98]. The reaction tolerated various pyrimidine containing arenes, such as indole, phenyl, and pyrrole with different ketenimines to form enaminylation products 61. Subsequently, the hydroarylation products 61 were further converted into bioactive

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• benzofused heterocycles (indole etc.) – such as benzimidazoles or tetrazolopyridines are often seen in medicinal chemistry. Singh et al. reported a method for preparing 3-arylnitrobenzimidazoles from 2-aminopyridines and nitroalkanes, using green LED Eosin Y photocatalysis, with molecular oxygen as the

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• ]. In spite of the fact that parent indole is too weak an acid to undergo Mitsunobu conversions, a model maleimide–indole hybrid was investigated by Ohkubo and colleagues to pave the way for the synthesis of indolo[2,3-a]pyrrolo[3,4-c]carbazole compounds with anticancer activity [90][91]. N-Glycosides

• of indole derivatives were also approached by Zembower et al. employing 2,3,4,6-tetra-O-benzyl glucopyranose in a Mitsunobu reaction [92]. In the same period, Prudhomme’s group followed closely related approaches for the N-glycosylation of indolic structures. Various rebeccamycin analogues were

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

• ligands, and tolerates a variety of substituents on both the indole and the iodonium salt. However, the atom-economy of the reaction is limited by the need to use the iodonium salts in slight excess (1.5 equivalents). Another multicomponent reaction has been designed for the preparation of

• indoles with diaryl-λ3-iodanes (Scheme 36) [75]. The reaction first involves the use of 20 mol % of CuI and 1.1 equivalents of di-tert-butylpyridine (dtbpy) to convert the indole to the C3–H arylated product. The released Ar–I building block, then, can be engaged in the subsequent step of N–H arylation by

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• (bromocresol green, 8), a bis-indole (indigo carmine, 9) and a naphthalene-bis-diazoic (naphthol blue-black, 10), in order to evaluate the outcome of molecular size, shape and electric charge. Dyes can be considered suitable and easily detectable models of pollutants [43][44][45][46][47], for the removal of

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

• ]. A selective C–H arylation at C3 of the indole was realised under copper catalysis before the addition of a ligand and an inorganic base initiated the N-arylation with the in situ formed iodoarene. The desired diarylated indoles 11 are obtained with an AE of 46% (for R1 = R2 = H, Ar1 = Ar2 = Ph). The

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• heteroarenes was realized using the benziodoxolone hypervalent iodine reagents indoleBXs. Functionalization of the C–H bond in bipyridinones and quinoline N-oxides catalyzed by a rhodium complex allowed to incorporate indole rings into aza-heteroaromatic compounds. These new transformations displayed complete

• -pyridinone ring is present in milrinone (1), used to treat heart failure, while a 4-pyridinone is part of mimosine (2), an alkaloid isolated from Mimosa pudica. A benzene-fused pyridinone – a quinolone – can be found in brexpiprazole (3), a drug used against schizophrenia. In addition, the indole core is

• transformations [22], but only one application of indole iodonium salts in copper catalysis by You and co-workers had been reported until 2017 [23]. In this context, indole-based benziodoxole hypervalent iodine reagents, recently introduced by Yoshikai's and our group [24][25][26][27], appeared ideal partners to

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• active natural tropone fused to indole rings (Figure 1). Benzo-annulated cycloheptanones (as colchicine [8], allocolchicine), benzo[7]annulenones, or benzotropones (as purpurogallin) and their analogues are present in a great variety of pharmacologically relevant natural products [27][28][29]. Colchicine

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• conjugates form layer-like structures during crystal formation via multiple hydrogen bonding interactions. This structural information indeed helps to design novel MGBs with much better binding affinity and specificity. A new family of conjugates between a Zn(II)-tach complex and (indole)2 or benzofuran

• –indole amide minor groove binders connected through alkyl or ethoxyethyl linkers were developed by Tecilla et al. [111]. The authors confirmed that these conjugates with tach units, either free or Zn(II)-complexed forms, bind strongly to the minor groove through electrostatic interactions with the

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• 2-phenylethanol (10), and the trace components acetophenone (9), terpinen-4-ol (13), and indole (16). For several other compounds in the headspace extract close hits for highly substituted aromatic compounds were found in our mass spectral libraries, but the mass spectra and retention indices for

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• -1H-indole in the presence of lithium perchlorate as catalyst to afford the new 3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones and 3-substituted indoles. The process was then extended to isocyanides and new aminobenzofurans formed via [4 + 1] cycloaddition were isolated. Bharate et al. reported

• indole polyheterocycles 49 and 50 in good yields with 90–99% ee. One of the latest publications around this topic has been reported by Deb et al. [86][87]. Various 2-(aminoalkyl)phenols or 1-(aminoalkyl)naphthols 51 were reacted with indoles under Brønsted acid catalysis resulting in 3-(α,α-diarylmethyl

• )indoles 52. Then, through C-2 cyclization of the indole ring using I2 as catalyst and tert-butyl hydroperoxide as oxidant, chromeno[2,3-b]indoles were isolated in 71–98% yields. In a different reaction pathway, starting from 3-(aminoalkyl)indoles 53 and phenols or naphthols, 3-(α,α-diarylmethyl)indoles 52

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -irradiated reaction of 5-aminopyrazoles 16, 2,2-dihydroxy-1-phenylethanone (98) and p-toluidine (99) under various polar and non-polar solvents with bronsted and lewis acid catalysts (Scheme 29). The reaction in dimethylformamide in presence of p-TSA resulted in the formation of azepino[5,4,3-cd]indole 100

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• -diacetylindoxyl [12] under basic conditions condensed with isatine to form quindoline-11-carboxylic acid easily transformed into quindoline (b) [12]. Another application of indole derivatives to the construction of quindoline starts with the reaction of 1-phenylsulfonylindole with 2-nitrobenzaldehyde (c) [13

• carbanions and nitroarenes, to indolo[3,2-b]quinoline derivatives. As starting nucleophile precursors, we have chosen derivatives of indole-2-ylmethyl phenyl sulfone (1a), tert-butyl indol-2-ylacetate (1b,c) and indol-2-ylacetonitrile (1d). As a model compound for screening of the reaction conditions, we

• materials disappeared (TLC control) and we isolated indolophenanthridine 16 in 41% yield. Other nitroarenes under analogous reaction conditions gave condensed indole derivatives as summarized in Table 2. Better yields were obtained in the reactions of 1-(tert-butoxycarbonyl)indol-2-ylacetonitrile with