Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• could be isolated (Scheme 34). Another class of heterocycles, α-silylated N-alkylated indoles 201–205 recently reported by Xu and co-workers, were formed using a nonracemic Cu–NHC catalyst through the enantioselective addition of the PhMe2Si group to α,β-unsaturated carbonyl indoles 200 (Scheme 35). The

• (L26) in combination with catalytic amounts of Cu(OAc)2 and stoichiometric Ph2SiH2 at ambient temperature to convert various alkenes to the desired enantiomerically pure silylated products (Scheme 40). A highly regio- and enantioselective dearomative silyation of indoles using NHC L27–ligated CuCl has

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• of N-[(3-aryl)propioloyl]indoles with AgSCF3 is described. This protocol allows for the synthesis of novel bis(trifluoromethylthiolated) or trifluoromethylthiolated pyrrolo[1,2-a]indol-3-ones in moderate to good yields. Mechanistic investigations indicated that radical processes were probably

• trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles to access SCF3-substituted pyrrolo[1,2-a]indol-3-ones (Scheme 1e). Results and Discussion On the outset, 1-(1H-indol-1-yl)-3-phenylprop-2-yn-1-one (1a) was chosen as the model substrate for optimization of the reaction conditions (Table 1). To our

•  1, entries 8 and 9). Gratifyingly, the yield was improved to 80% by reducing the amount of base to 1.0 equivalent (Table 1, entry 10). With the optimized reaction conditions in hand, we then set out to explore the substrate scope of N-[(3-aryl)propioloyl]indoles (Scheme 2). First, we explored the

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• BODIPY core has not yet been achieved. Inspired by the works of Waser and co-workers showing the gold(I)-catalyzed C–H electrophilic alkynylation of various heterocycles (e.g., pyrroles, indoles, etc.) with ethynylbenziodoxolone (EBX) as an activated ethynyl synthon [38][39][40][41][42], we investigated

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• reaction in photocatalysis, the oxidation of N-aryl tetrahydroisoquinoline (Scheme 31) [45]. Upon oxidation, the in situ-formed iminium ion was reacted with nitroalkanes, enamines, and indoles. In all cases, the 1-substituted tetrahydroisoquinolines were isolated in good to excellent yields. The reaction

• α-amino radical that is then oxidized to the dihydroisoquinolinium species. Then, the latter reacted with the nucleophile (nitroalkanes, catalytically in situ-formed enamines and indoles) to furnish the product. 2.4 Proton-coupled electron transfer (PCET) The PCET reaction is an interesting and

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• coumarins and indoles: Coumarins and indoles are a large class of compounds gifted with a rich and attractive chemistry. They are found in numerous bioactive natural and nonnatural products. Therefore, a lot of work has been devoted to the construction of diverse intricate molecules containing these

• scaffolds in their structures [104][105][106][107]. By employing dual photoredox catalysis, in 2016, Fabry et al. reported the cyclization of substituted anilides with alkynes to produce indoles [108]. Unlike previously reported syntheses, viz, an indole synthesis by the Fagnou group utilizing a large

• thiolation. Synthesis of indoles via C–H cyclization of anilides with alkynes. Preparation of 3-trifluoromethylcoumarins via C–H cyclization of arylpropiolate esters. Monobenzoyloxylation without chelation assistance. Aryl-substituted arenes prepared by inorganic photoredox catalysis using 12a. Arylation of

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• are biologically and medicinally very important compounds, and their syntheses have received considerable attention. Herein, we report the synthesis of 3-alkenylindoles via a regioselective alkenylation of indoles, catalysed by a ruthenium nanocatalyst (RuNC). The reaction tolerates several electron

• following three categories: (i) by Wittig or Doebner reaction of indoles bearing a 3-aldehyde group; (ii) by 1,4- or 1,2-addition of α,β-enones or carbonyl compounds, followed by oxidation or elimination, respectively; (iii) by Pd-catalysed oxidative coupling of indoles with activated alkenes. Several

• catalyst [16]. However, this strategy was associated with several shortcomings, as it required two to four successive steps for the synthesis of the 3-indolecarbaldehydes starting form indoles, low yields, a narrow scope, and selectivity issues among the geometrical isomers, which led to troubles in

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• for the synthesis of pharmaceutically relevant benzo[4,5]furo[3,2-b]indoles in moderate to very good yield. The synthesized compounds have been analyzed with regard to their inhibitory activity (IC50) of nucleotide pyrophosphatases h-NPP1 and h-NPP3. The activity lies in the nanomolar range. The

• diindolofurans by regioselective Suzuki–Miyaura couplings of tetrabromofuran and subsequent cyclization by tetrafold Buchwald–Hartwig reaction [31]. We also studied the synthesis of benzo[4,5]furo[3,2-b]indoles by a similar concept. However, while performing our studies, Truong et al. reported the synthesis of

• synthesis of benzo[4,5]furo[3,2-b]indoles by double Buchwald–Hartwig reaction was studied next. The conditions were optimized for the reaction of 3 with p-toluidine (4b, Scheme 1, Table 1). The amount of ligand and palladium precursor was optimized using different solvents (dioxane, toluene, and DMF

Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

• Nadezhda S. Demina,
• Nikita A. Kazin,
• Nikolay A. Rasputin,
• Roman A. Irgashev and
• Gennady L. Rusinov

Beilstein J. Org. Chem. 2019, 15, 2678–2683, doi:10.3762/bjoc.15.261

• ketones were used to synthesize new N,S-heterotetracenes, namely 9H-thieno[2',3':4,5]thieno[3,2-b]indoles by their treatment with arylhydrazines in accordance with the Fischer indolization reaction. Keywords: Fiesselmann thiophene synthesis; Fischer indole synthesis; N,S-heteroacene; thieno[3,2-b

• -substituted TT building blocks, which can be utilized for the construction of various fused systems, including N,S-heteroacenes, e.g., substituted 9H-thieno[2',3':4,5]thieno[3,2-b]indoles (TTIs) (Figure 1). Results and Discussion Continuing our previous work in which we used the Fiesselmann thiophene

• the synthesis of aryl-substituted 9H-thieno[2',3':4,5]thieno[3,2-b]indoles. These π-conjugated ring-fused molecules are of interest as electron-rich subunits for further organic semiconductors development. An example of an earlier developed S,N-heterohexacene [13] and general structure of compounds

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• the C–H activation event to the trifluoromethylated products, as described in Scheme 63. In this case, the specific catalytic mechanism remains to be studied. In 2011, the group of Liu [123] accomplished a Pd(II)-catalyzed oxidative trifluoromethylation of indoles with TMSCF3 and PhI(OAc)2 at room

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• functionalization [3][4][5][6]. The metal carbene reactions with indoles have been studied for the three types of carbenoids: acceptor–acceptor [7][8][9], mono-acceptor [10] and donor–acceptor carbenoids [11][12][13][14]. Depending on the metal and the diazo compound, the chemo- and regioselectivity in the metal

• derived from ethyl α-halodiazoacetates (X-EDA) react readily with unprotected indoles to form ethyl 3-carboxyquinoline structures (Scheme 1) [15]. The Rh carbenes derived from X-EDAs stand out from the three other types of classified carbenoids with respect to chemoselectivity in reactions with indoles

• . These halo-acceptor carbenoids undergo cyclopropanation of N–H indoles with high selectivity, and only traces of C–H or N–H insertion products were observed. The yield of ethyl quinoline-3-carboxylate is dependent on the halogen in X-EDA (Cl: 90%, Br: 84%, I: 70%). The reaction works well for

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

• Hai-Yun Huang,
• Haoran Li,
• Thierry Roisnel,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2019, 15, 2069–2075, doi:10.3762/bjoc.15.204

• functionalization of heteroarenes such as thiophenes, furans, pyrroles and indoles [14][15], this methodology has been widely applied for the preparation of new aryl-substituted heteroarenes [16][17][18][19][20][21]. Several results dealing with the C–H bond functionalization of indoles have been reported allowing

• to prepare either α- [22][23][24][25][26][27][28][29][30][31] or β-arylated [32][33][34][35][36][37] indoles, depending on the reaction conditions. However, to the best of our knowledge, no example of regioselective α- or β-arylations via the C–H bond functionalization of lilolidine has been reported

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• constructing tetracyclic aromatic heterocycles containing selenium. For example, the reaction of 2-(2-iodophenyl)indoles with selenium powder in the presence of CuO as catalyst resulted in benzoselenopheno[3,2-b]indole derivatives [14]. The reaction of 2-(2-haloaryl)imidazo[1,2-a]pyridines with selenium using

Identification of optimal fluorescent probes for G-quadruplex nucleic acids through systematic exploration of mono- and distyryl dye libraries

• Xiao Xie,
• Michela Zuffo,
• Marie-Paule Teulade-Fichou and
• Anton Granzhan

Beilstein J. Org. Chem. 2019, 15, 1872–1889, doi:10.3762/bjoc.15.183

• varies within the series. Our results clearly point to several structural motifs that appear advantageous for high fluorimetric response and high quantum yield of the probes. First of all, indole substituents, including core-substituted indoles, emerge as the most efficient in this sense, as demonstrated

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• , recyclable catalyst in the N-arylation of indoles [45][46]. Copper catalysts have shown exceptional enantioselectivity for reactions such as hydrosilylation, hydroboration, and heterogeneous as well as homogeneous hydrogenation [47][48][49]. Also, the copper salts found used as oxidants in a number of

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• when using C,N-, N,S- and N,N-dinucleophiles. It is characterized by a selective 5-endo-dig cyclization to the corresponding five-membered rings. The obtained new compounds are of special interest due to the practical utility of the formed fused heterocycles, such as indoles [1], thiazolo[2,3-b][1,3,4

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• , indoles [30] or phenols [31]. Other arenes (benzene and its substituted derivatives) have not been involved in these reactions. Concerning electron-deficient allenes, bearing electron-withdrawing groups, there is only one example of a trifluoroacetic acid-promoted hydroarylation with indoles [30]. To the

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• developed [26]. Since then the development of 5-HT3R antagonists progressed. The first-generation antagonists are structurally categorized in three major classes: (I) carbazole derivatives (e.g., ondansetron), (II) indazoles (e.g., granisetron), and (III) indoles (e.g., dolasetron) [26][30]. Generally, 5

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• State University, Kent, OH 44242, USA 10.3762/bjoc.15.60 Abstract A series of giant tris(heteroaryl)methanes are easily assembled by one-pot three-component synthesis by simple reflux in ethanol without catalyst or additives. Diversely substituted indoles (Ar1) react with quinoline aldehydes, quinolone

• aldehydes, chromone aldehydes, and fluorene aldehydes (Ar2CHO) and coumarins (Ar3) in 1:1:1 ratio to form the corresponding tris(heteroaryl)methanes (Ar1Ar2Ar3)CH along with (Ar1Ar1Ar2)CH triads. A series of new 2:1 triads were also synthesized by coupling substituted indoles with Ar2CHO. The coupling

• ternary heteroarylmethane-inspired hybrids by coupling diversely substituted indoles (Ar1) with quinoline aldehydes, quinolone aldehydes, chromone aldehydes, and fluorene aldehydes (Ar2CHO) and coumarins (Ar3) in 1:1:1 ratio by simple reflux in ethanol solvent to form the corresponding highly crowded tris

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

• oxidative conditions has been developed. The employment of Mn(OAc)3·2H2O or KMnO4 as stoichiometric oxidants allowed the use of a wide range of nucleophiles, such as nitromethane, (aza)indoles, pyrroles, phenols, pyrazole, indazole and diethyl malonate. The formation of the target compounds presumably

• -(cyanomethyl)pyridinium chloride, o-hydroxybenzaldehydes, and nitromethane. Scope of the reaction of o-hydroxybenzaldehydes with N-(cyanomethyl)pyridinium chloride and indoles. a2 equiv Mn(OAc)3·2H2O was used as an oxidant at step 2; bisolated as inseparable mixture with 4; cstep 2 performed at 0 °C for 5 days

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

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

• -oxopropanenitriles 3 were synthesized from the reaction of indoles 1 and 2-cyanoacetic acid (2) in acetic anhydride under heating conditions (Scheme 1) [73]. Subsequently the one-pot four-component reaction of 3-(1H-indol-3-yl)-3-oxopropanenitrile (3a), 4-chlorobenzaldehyde (4f), cyclododecanone (5a) and ammonium

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

• Camila S. Pires,
• Daniela H. de Oliveira,
• Maria R. B. Pontel,
• Jean C. Kazmierczak,
• Roberta Cargnelutti,
• Diego Alves,
• Raquel G. Jacob and
• Ricardo F. Schumacher

Beilstein J. Org. Chem. 2018, 14, 2789–2798, doi:10.3762/bjoc.14.256

• /direct selanylation is a practical and economical way to incorporate organylselanyl moieties in aryl and heteroaryl compounds avoiding the necessity of pre-functionalization, multistep synthesis and tedious work-up [4][5]. In this context, the preparation of diverse selanylated indoles and

Synthesis of aryl sulfides via radical–radical cross coupling of electron-rich arenes using visible light photoredox catalysis

• Amrita Das,
• Mitasree Maity,
• Simon Malcherek,
• Burkhard König and
• Julia Rehbein

Beilstein J. Org. Chem. 2018, 14, 2520–2528, doi:10.3762/bjoc.14.228

• charge transfer using Cs2CO3 as base [41]. Two recent reports showed the synthesis of C-3 sulfenylated indoles and 3-sulfenylimidazopyridine via C–H functionalization using Rose Bengal as photocatalyst [42][43]. In general, the arylation reactions use the reductive cycle of the photocatalyst and for this

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

• different from the previously reported Pd-catalyzed sequential reaction of the same substrates with Ar–I, Ar–Br and ArN2+BF4−, that afforded 12-arylindolo[1,2-c]quinazolin-6(5H)-ones. Moreover, 12-unsubstituted indolo[1,2-c]quinazolines can be obtained both by reacting 2-(o-aminophenyl)indoles with DMFDMA

• or by sequential Pd-catalyzed reaction of o-(o-aminophenylethynyl)aniline with DMFDMA. Keywords: arylboronic acids; DMFDMA; indoles; indoloquinazolines; quinazolines; Introduction Indoloquinazoline derivatives constitute an important class of compounds which exhibit a wide range of biological

• 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

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

• pyridine as an additive (Scheme 6) [46]. Similarly, benzothiazoles also efficiently underwent hydroheteroarylation by using suitable ligands [47]. The reaction was successfully extended to indoles and benzimidazoles 7 bearing a removable 2-pyrimidyl (2-pym) directing group with alkynes at ambient

• ) for C–H functionalization [37]. The Co(III) catalyst was applied for the hydroarylation of alkynes with indoles 14 to form alkenes 15 with linear selectivity (Scheme 11) [53]. The reaction features a broad substrate scope including a variety of indoles, terminal and internal alkynes, mild reaction

• limited to terminal alkynes. Additionally, they applied this methodology to design a mitochondria-targeted imaging dye from electron-withdrawing formyl-substituted indoles and alkynes. Later, Maji’s group reported an N-tert-butyl amide-directed mono- and di-alkenylation reactions using a cobalt catalyst