Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• methanesulfonyl chloride mediated cyclization of amide 97 and reaction with methyl iodide or methoxymethyl chloride afforded the N-substituted indole derivatives 99 (R = Me, MOM). The desired phosphinylated compounds 102 were obtained via three routes: The dicyclohexylphosphine derivatives 102a and b were only

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• heterocycle. This intermediate was then trifluoromethylselenylated by [(bpy)CuSeCF3]2. While benzofurans and benzothiophenes were prepared in moderate to good yields, only marginal yields were obtained with indole derivatives (up to 25%). Finally, the reactions could easily be scaled up to a gram scale. The

Copper-catalyzed enantioselective conjugate addition of organometallic reagents to challenging Michael acceptors

• Delphine Pichon,
• Jennifer Morvan,
• Christophe Crévisy and
• Marc Mauduit

Beilstein J. Org. Chem. 2020, 16, 212–232, doi:10.3762/bjoc.16.24

• enantioselective catalysis was reported by Evans and co-workers in 2005 [34]. The selected asymmetric transformation was the Friedel–Crafts 1,4-addition involving indole derivatives as nucleophiles, catalyzed by a scandium(III) triflate complex with chiral bis(oxazolinyl)pyridine ligands. As highlighted by Evans

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

• reaction was also carried out using [Ru(p-cymene)Cl2]2 as a homogeneous catalyst, but this also did not lead to the formation of the desired product. After establishing the optimum conditions for the reaction, we carried out the alkenylation of several indole derivatives 1 with different acrylates 2 under

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

• ten benzo[4,5]furo[3,2-b]indole derivatives based on regioselective Suzuki–Miyaura reaction of 2,3-dibromobenzofuran with 2-bromophenylboronic acid and subsequent cyclization. The difference between the work of Truong and our approach mainly lies in the synthesis of the cyclization precursor. The

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

• of indole substituents on the yields of ethyl quinoline-3-carboxylates [15]. Green = good, orange = medium, red = poor. R = halogen, Me, MeO, NO2. Retrosynthetic outline for the synthesis of quinolone-3-carboxlates from indole derivatives. Synthesis of ethyl 4-quinolone-3-carboxylate (6) and proposed

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

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

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• three-component reaction of 2-iodobenzamide 17, terminal alkyne 18 and pyrrole or indole derivatives 19. Palladium-catalysed three-component reaction of ethynylbenzamides 21, secondary amines 22 and CO (23). Proposed mechanism for the formation of methyleneisoindolinones 24. Copper-catalysed three

• quaternary centre [79]. The reaction takes places in water, even in the presence of air, and with nanodomain cuprous oxide as an inexpensive and reusable catalyst. The scope includes aryl, alkyl and carboxyl groups at 2- and 3-positions of the lactam ring. Pyrrole reacts across the 2-carbon while indole

• derivatives do it through the carbon at 3-position. Although a quaternary stereocentre is created in the process, no attempts to make this synthesis in a stereoselective fashion were reported. A tentative mechanism is proposed, based in a Sonogashira coupling of iodobenzamide 17 and copper acetylide, in a

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

• -(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

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

• 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

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

• 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

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

• to heteroaromatic substrates like indoles would produce valuable synthetic intermediates. By applying Rose Bengal as organic photocatalyst and aerobic oxygen as terminal oxidant, they were able to functionalize a series of indole derivatives and also could show the applicability of the thiocyanation

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• , said reagent was used under reductive conditions in order to generate in situ the highly reactive CF3SCl, which could subsequently be trapped by nucleophiles. Indole derivatives proved to be appropriate substrates for this reaction, and a variety of them were selectively converted into their 3

• derivatives. Morevover, the scope could be extended to other substrates of interest, such as activated benzene derivatives and thiols. Similarly, Lu, Zhao and co-workers found out that excellent yields could also be achieved for indole derivatives when replacing PMe3 or (EtO)2P(O)H by cheap and stable

• of CF3SO2Cl and tricyclohexylphosphine, the trifluoromethylsulfinylation of various indole and pyrrole derivatives featuring diverse functional groups, as well as other azaarenes could be achieved in low to excellent yields (Scheme 38a). Generally, indole derivatives provided better results than

Synthesis and photophysical properties of novel benzophospholo[3,2-b]indole derivatives

• Mio Matsumura,
• Mizuki Yamada,
• Atsuya Muranaka,
• Misae Kanai,
• Naoki Kakusawa,
• Daisuke Hashizume,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2017, 13, 2304–2309, doi:10.3762/bjoc.13.226

• knowledge, the synthesis of benzophosphole-fused indole derivatives as tetracyclic heteroacenes has not been reported. In 2015, Lu et al. reported the synthesis of only one phosphole and indole-fused pentacyclic heteroacene [35]. Recently, we reported simple and efficient synthetic routes to benzothiophene

• -ray crystal analysis of benzophospholo[3,2-b]indoles showed that the nitrogen atoms are sp2 hybridized and the phosphorus atoms adopt pyramidal and tetrahedral geometry. A significant characteristic of the benzophosphole-fused indole derivatives is that the corresponding phosphine oxide, the

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

• isolate up to 77% of differently substituted indole derivatives (Scheme 55). Advantages and limitations Over a couple of decades the area of mechanochemistry considered to be one of the best solvent-free synthetic methods. This area has become significantly interesting to chemists due to its benefits over

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• propargyl–allenyl rearrangement [17][18][19][20][21][22][23][24][25][26][27] and an allyl migration [32][33][34] (Scheme 1). In addition, phosphine-substituted indole derivatives could also be conveniently constructed by a similar strategy. This method not only avoids the use of transition metal catalysts

• allyl migration (Scheme 2). Phosphine-substituted indole derivatives were obtained in moderate yield (Figure 3, 4a–c). Conclusion In summary, we have developed an expedient route for the construction of benzothiophene and indole derivatives via propargyl–allene rearrangement and allyl migration. The

• reaction proceeded under mild conditions to produce useful benzothiophene and indole derivatives. Examples of biologically active benzothiophene derivatives. Synthesis of benzothiophenes. Reaction conditions: 1 (0.5 mmol), DBU (0.1 mmol), THF (2.0 mL), 50 °C, 12 h, under N2. Yields are isolated yields

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• halides. Successive reaction with terminal alkynes in the presence of t-BuOK affords the corresponding alkyl alkynyl selenide in moderate to good yields. Finally, this methodology allowed the synthesis of 2-alkylselanyl-substituted benzofuran and indole derivatives starting from convenient 2-substituted

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• of the azomethine ylide intermediate and a plausible reaction pathway for the formation of the spiranes is depicted following the retrosynthetic strategy in Scheme 2. The applicability of the cycloaddition reaction was explored first for indole derivatives 7a–d and then extended to the synthesis of

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. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• continues to be a prolific source of bioactive secondary metabolites with diverse structures. In this paper, two indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivatives, varioloids A (1) and B (2), were isolated from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291. The

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• enantioselectivities (>95:5 dr, up to 98:1 er). Very recently, Shi et al. revealed an unprecedented acid-promoted intermediate-dependent unusual [4 + 3], [3 + 2] and cascade reactions of 3-indolylmethanols with Nazarov reagents, leading to the construction of diverse indole derivatives (Scheme 56) [73]. 3

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• derivative 4 to develop the first organocatalytic enantioselective Friedel–Crafts (F–C) alkylation of indoles, employing nitroalkenes as versatile electrophiles. In the presence of catalyst 4, the differently functionalized indole derivatives 2 reacted with aryl and alkyl nitroalkenes 3 in dichloromethane at

• indole derivatives 2. Indeed, as discussed below, other authors proposed the compound 6 as a plausible bifunctional catalyst. The Enders’ group used its enantiomer (ent-6) to develop a pioneering scalable one-pot multicatalytic method for the C2/C3-annulation of the indoles 2 (Scheme 4) [26]. In this

• central nervous system diseases [30][31][32][33][34]. In the proposed reaction pathway, the nucleophilic addition of the indole derivatives 2 to the nitroalkene 13 progresses in a stereocontrolled manner due to the creation of a ternary complex with the chiral bifunctional thioamide ent-6 (TS4, Scheme 7

Active site diversification of P450cam with indole generates catalysts for benzylic oxidation reactions

• Paul P. Kelly,
• Anja Eichler,
• Susanne Herter,
• David C. Kranz,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2015, 11, 1713–1720, doi:10.3762/bjoc.11.186

• ) fingerprinting of these libraries against substrates for a broad substrate panel, activity and chemo-, regio- and stereoselectivity. The production of indigo from indole derivatives 1–4 by P450s can be considered as an effective visual screen for identifying interesting new mutants from diverse libraries. Indole

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• The synthesis and reactivity of indole derivatives substituted in the benzene section was studied. Starting materials 4- and 6-iodoindole were conveniently prepared via the Batcho–Leimgruber route and purified by sublimation. Novel vicinally indolyl-substituted cyclopentanols with unexpected cis

• . Conclusion Indole derivatives prenylated at the benzene section could become important for the biomimetic synthesis of dimeric natural products such as the raputindoles from the plant Raputia simulans. Characteristically, the three enamine positions of the indole moieties of the raputindoles are

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• antiproliferative activity, with no significant difference between the pyrrole and indole derivatives. Conclusion Unlike other azoles such as pyrazole and triazoles [37][38][40], pyrrole and indole do not possess any atom capable of coordinating metals. As a consequence, the corresponding CH acidities in THF

• substrates. Consequently, the Gibbs energy of the homodesmic reaction (ΔGr,sol) and the pKa value are related by the following equation: Biological evaluation. The antiproliferative activity of N-arylated pyrrole and indole derivatives was studied in the A2058 (ATCC® CRL-11147) cell line as described