Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• -poor N-aryloxyamides 160, indole derivative 161, and carbonate or other multicharge anions in CH3CN (Scheme 56). The corresponding products can be given in good yield by modifying substituents on the amide moiety in 160 or N-substituted indoles. Inorganic-base electron donors formed transient complexes

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• progressive conversion of the starting material into the C6-derivative 64 (Scheme 18). Chen et al. reported the synthesis of C2-phosphorylated indoles via 1,2-phosphorylation of 3-indolylmethanols with H-phosphine oxides or H-phosphonates under Brønsted acid activation [72]. The scope of the reaction includes

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• reaction of propargyl ester derivatives (Figure 1a) [17][18][19][20][21][22][23][24], and we have exploited such a methodology for the synthesis of bruceollines H and I from 3-substituted indoles (Figure 1b) [25][26]. Our computational study showed that the Nazarov reaction is fast with the 2-substituted

All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

• 64% yield over three steps. The conversion of 138 to sinensilactam A (20) was achieved in two steps. Platinum-catalyzed [3 + 2] cycloaddition The platinum-catalyzed intermolecular [3 + 2] cycloaddition of propargyl ether derivatives and vinyl ether producing polycyclic indoles was disclosed by

A novel and robust heterogeneous Cu catalyst using modified lignosulfonate as support for the synthesis of nitrogen-containing heterocycles

• Bingbing Lai,
• Meng Ye,
• Ping Liu,
• Minghao Li,
• Rongxian Bai and
• Yanlong Gu

Beilstein J. Org. Chem. 2020, 16, 2888–2902, doi:10.3762/bjoc.16.238

• tricyclic indoles bearing 3,4-fused seven-membered rings, 2‑arylpyridines, aminonaphthalenes and 3-phenylisoquinolines. In addition, this catalyst showed to be recyclable and could be reused several times without significant loss in activity during the course of the reaction process. Keywords: biomass

• were shown in Scheme 1. Aldehydes 2 with different functional groups on the benzene ring could react smoothly with compounds 1a and 3a, producing the corresponding 3,4-fused tricyclic indoles 4b–d with yields ranging from 46% to 64%. o-Anisaldehyde, with steric-hindrance effect, also reacted

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• ketones 29 with 2-substituted indoles 30 as a precursor to imine 31, for the synthesis of indolin-3-ones 32 in good yields and excellent enantioselectivities (21 examples, up to >99:1 er) (Scheme 4a) [29]. Zhang et al. recently added to the scope of this family of reactions with their use of aldehydes

• -catalysed Povarov reaction rather than with its own tautomer (Scheme 21a) [70]. Zhang and You developed a catalytic dearomatisation reaction of indoles 150 using similar chemistry, where the generated imine 151 now reacts intramolecularly with a pendant nucleophile and is further oxidised to a carbocation

• intermediate 239•, which abstracts a hydrogen atom from TRIP-thiol to produce enantioenriched cyclic sulfonamides 239 in excellent yields and enantioselectivities (28 examples, up to 98:2 er). Chiral phosphates have also been used to catalyse the enantioselective nucleophilic addition of indoles 241 to imines

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• precursor for nitrogen heterocycles. As a part of our synthetic design towards the construction of five-membered heterocycles, we have previously reported the synthesis of highly substituted imidazoles [6], indoles [7] and pyrroles [8] starting from different azidochalcones. In continuation, employing α

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• general strategy, in 2014, Rueping and co-workers reported the pioneering contribution concerning the synthesis of indoles via an intramolecular C–H/C–H oxidative coupling of N-arylenamines under air atmosphere. This procedure was based on dual catalysis involving a double C–H activation system and

• et al., allowing the synthesis of N-heterocycles such as indoles and pyrroles. The targeted heterocyclic products were obtained by cyclization of acetanilides with alkyne derivatives via a direct ortho-metalation pathway (Figure 17) [79]. Acetyl substituents acted as DG in this transformation

• -poor aromatic or aliphatic aldehydes were potent coupling partners for this procedure. The transformation also allowed the introduction of heterocyclic moieties at the C2-position of indoles, hence exhibiting a wide substrate scope of this coupling. The proposed mechanism of this acylation is shown in

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• amines, producing the corresponding substituted indoles 6a and 6c–f in 41–54% yield (Scheme 4). The yield of the indolones 7a and 7c–f was found almost constant (10–14%) with all amines involved. It is worthy of note that the two compounds were easily separated using usual chromatographic techniques. The

• directing the reaction exclusively towards indole formation by reacting the diketone with appropriate substrates, combining a primary amine with a tertiary amine or a pyridine separated by several spacer arms (Scheme 6). Under these conditions, the functional indoles 6h–l were obtained exclusively in 45–55

• ; indoles 6, indolones 7, and cinnolines 8, starting from common substrates 1,4-diketones 5 and primary amines. The protocols developed here used mild conditions, were functional-group tolerant, transition-metal-free, proceeded in moderate to good yield, and could therefore easily be used in medicinal

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• - and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels–Alder and Heck arylation reactions. 3-(N-Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly endo-Diels–Alder cycloaddition with maleimides to furnish octahydropyrrolo

• [3,4-e]indoles, which served as precursors in the regioselective synthesis of aza-polycyclic skeletons via an intramolecular Heck arylation reaction. Through the latter reaction, the 3-(N-benzyl-2-pyrrolyl)acrylates give rise to 3-(pyrrolo[2,1-a]isoindol-3-yl)acrylates. A further oxidative

• aromatization of the polycyclic intermediates provides the corresponding polycyclic pyrrolo-isoindoles and isoindolo-pyrrolo-indoles. A theoretical study on the stereoselective Diels–Alder reactions, carried out by calculating the endo/exo transition states, revealed the assistance of non-covalent interactions

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• fragmentation, or H-abstraction (Scheme 16). A common way to access such radicals is through the decarboxylation of α-keto acids. Both reductive and oxidative strategies were implemented. In 2016, Wang and co-workers developed an organophotocatalyzed acylation of indoles (Scheme 17) [89]. They successfully

Palladium-catalyzed regio- and stereoselective synthesis of aryl and 3-indolyl-substituted 4-methylene-3,4-dihydroisoquinolin-1(2H)-ones

• Valeria Nori,
• Antonio Arcadi,
• Armando Carlone,
• Fabio Marinelli and
• Marco Chiarini

Beilstein J. Org. Chem. 2020, 16, 1084–1091, doi:10.3762/bjoc.16.95

• aminopalladation/reductive elimination. Keywords: alkynylanilines; arylboronic acids; indoles; isoquinolinones; palladium; Introduction The isoquinolinone nucleus is a key constituent of many natural products [1][2][3] and pharmaceuticals [4][5][6]. Substituted isoquinolinones have been found in biologically

• chemical and physical properties of the products. Furthermore, over the years, we have reported a general methodology for the Pd-catalyzed synthesis of 3-substituted indoles, now referred to as the “Cacchi reaction” [34], through an aminopalladation/reductive elimination sequence starting from 2

• , widening in such a way the scope of the methodology and allowing challenging synthesis of indoles 6 bearing a 4-alkylidene-3,4-dihydroisoquinolin-1(2H)-one substituent (Scheme 1b). It is worth noting that an aerobic Pd/Cu-catalyzed cyclizative cross-coupling between 2-alkynylanilines and 2

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• reactions between N-phenyltetrahydroisoquinoline and dimethyl malonate, nitromethane, indoles, and dialkyl phosphonates furnished the α-substituted N-phenyltetrahydroisoquinolines in yields equal or better than with the originally used photocatalysts, such as eosin and Ir-complex [29][30][31] (Scheme 10

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• , D-53121 Bonn, Germany 10.3762/bjoc.16.71 Abstract A new, mild and efficient protocol for the synthesis of trifluoromethyl(indolyl)phenylmethanols by the reaction of indoles with a variety of aromatic fluoromethyl ketones in the presence of K2CO3 (15 mol %) and n-Bu4PBr (15 mol %) in water. The

• at the position 3 of indoles [1][2][3][4]. Friedel–Crafts alkylation of (1H-indol-3-yl)methanols with indoles has proven to be a powerful strategy for the preparation of biologically important 3,3′-diindolylmethanes (DIMs) [5][6][7][8][9][10][11][12][13][14]. Additionally, (1H-indol-3-yl)methanols

• be synthesized by Friedel–Crafts hydroxyalkylation reactions of indoles with trifluoromethyl ketones in the presence of either Lewis/Bronsted acid catalysts. Bandini et al. reported the trifluoromethyl hydroxyalkylation of indoles catalyzed by an organic base 2-tert-butyl-1,1,3,3-tetramethylguanidine

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