Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• ]. Benzimidazoles are an important class of organic materials, and many derivatives of these group are biologically active [6][7][8][9]. The benzimidazole moiety “ […] is isosteric with indole and purine nuclei, which are present in a number of fundamental cellular components and bioactive compounds. Indeed, a

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• -Nitrophenyl)thieno[3,2-b]thiophene (18) was similarly prepared by Pd-catalyzed Stille-type reaction of monostannylated thienothiophene 14 and o-iodonitrobenzene (17) in 86% yield. Successive Cadogan cyclization of 18 with triethyl phosphite under reflux gave tetracyclic 9H-thieno[2’,3’:4,5]thieno[3,2-b]indole

• heterotetracenes TTA, 9, 13, 19, 22, and 33, and heterohexacene 22. Synthesis of fused S,N-heterotetracene SN4 9 starting from thieno[3,2-b]thiophene (1). Synthesis of parent H-SN4 13 via the azide route. Synthesis of tetracyclic H-SN4 13 via the Cadogan route. Synthesis of tetracyclic indole derivative 19 via the

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• and glutamine as well as the indole NH of tryptophan and some of the arginine NHε. This spectrum is also known as an amide finger print spectrum of a protein because the chemical shifts of the amides are very sensitive to both the secondary and tertiary structure. The amide signals, particularly for

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

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

• , thus rendering this methodology well suitable for the synthesis of a variety of indole derivatives. Subsequently, the panel of oxidative Heck coupling reactions via a photoredox catalytic system combined with C–H activation using Rh [74] or Ru [75] was extended by Rueping’s group. In 2014, Rueping

• applied to various C–H functionalization reactions [92][93]. In 2017, Noël, Van der Eycken and co-workers hence astutely combined the dual catalysis strategy with flow microreactor technology to achieve C2-acylation of indole derivatives with aldehydes (Figure 30) [94]. Both electron-rich and electron

• Figure 31. As previously, distinct catalytic cycles involving photoredox catalysis and C–H activation act in a cooperative way to promote the formation of a new bond. The strategy is based on the presence of a pyrimidine DG at the N1-position of the indole in order to facilitate the C–H activation step

Et₃N/DMSO-supported one-pot synthesis of highly fluorescent β-carboline-linked benzothiophenones via sulfur insertion and estimation of the photophysical properties

• Dharmender Singh,
• Vipin Kumar and
• Virender Singh

Beilstein J. Org. Chem. 2020, 16, 1740–1753, doi:10.3762/bjoc.16.146

• excellent light-emitting properties with quantum yields (ΦF) up to 47%. Keywords: benzothiophene; β-carboline; metal-free; photophysical properties; sulfur insertion; Introduction The pyrido[3,4-b]indole moiety, commonly referred as β-carboline, is the core unit of about one quarter of all natural

• round-bottomed flask; 2-nitroacetophenone (0.080 mL, 0.587 mmol) was added at room temperature and the reaction mixture was stirred for 15 min. Thereafter, methyl 1-formyl-9-methyl-9H-pyrido[3,4-b]indole-3-carboxylate (1b, 0.15 g, 0.560 mmol) was added portionwise and the reaction mixture was allowed to

• gel (CHCl3/MeOH 95:5, v/v) to afford the analytically pure product 2bA as orange solid in 74% yield (two step yield). One-pot experimental procedure for the synthesis of methyl 1-(benzo[b]thiophene-2-carbonyl)-9H-pyrido[3,4-b]indole-3-carboxylate (6C). To a stirred suspension of Cs2CO3 (0.182 g, 0.560

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

• construction of nitrogen-containing heterocycles from common substrates: 1,4-diketones and primary amines. Indeed, by just varying the substrates, the substituents, or the heating mode, it is possible to selectively synthesize indole, indolone (1,5,6,7-tetrahydroindol-4-one), or cinnoline (5,6,7,8

• -tetrahydrocinnoline) derivatives in moderate to excellent yields. Keywords: cinnoline; 1,4-diketone; indole; indolone; N-heterocycle; Introduction Nitrogen-containing heterocycles are widespread in plenty of molecules of interest, either in materials science, optics, electronics, or biology [1][2][3][4]. They are

• also very useful building blocks to create more sophisticated organic molecules. Therefore, the search for efficient methods for the synthesis of nitrogen-containing heterocycles is crucial to both organic and medicinal chemists. Among these, indole, indolone (1,5,6,7-tetrahydroindol-4-one), and

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• to afford intermediate isoindole 4a [2][3][4][5][6]. Then, the addition of water to the sterically less-hindered site of the latter compound followed by ring opening resulted in the rearranged aldehyde 2a [1]. As regards the formation of dimer-like product 3a, the tendency of pyrrole [7][8], indole

• dimerization of indole under acidic conditions (Scheme 7) [8]. Electrophilic attack of indole protonated at position 3 toward the position 3 of another indole molecule, followed by deprotonation affords dimer-like derivative 20. The fundamental difference of this transformation from that we observed in the

• -like products 8a,b. Dimerization of indole under acidic conditions. Reaction of o-(pivaloylaminomethyl)benzaldehyde (1e) to give dimer-like products 23a and 23b. Yields of rearranged aldehydes 2 and dimer-like products 3 and 8 in two different solvents. Relative Gibbs free energy values corresponding

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• ], antiprotozoal [47], antidiabetic [48], and antitubercular [49]. Relevant is the role of the hydrazone moiety as antitumor agent [50][51][52][53]. An interesting example reported by Ferreira demonstrates that the chemical derivatization of the indole alkaloids dregamine and tabernaemontanine to yield new

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

• that are known to have varied and robust pharmacological activity, such as isoborreverine (1) [12], mitomycin A (2) [13] and chlorizidine A (3) [14]. The indole moiety is incorporated into their structure, which is important because it is a seminal heterocycle that exhibits a wide range of biological

• representative example of the less common approach for the construction of the indole skeleton on substituted pyrroles by generating the benzene ring via an annulation process [36][37][38][39]. Due to our interest in transforming simple five-membered heterocycles into natural products [40][41] and complex aza

• yields. Once having the optimal reaction conditions for the palladium(0)-catalyzed cross-coupling reaction leading to the cyclization of N-(2-bromobenzyl)pyrroles 8, the endo-octahydropyrrolo[3,4-e]indole-1,3-diones 9g–j and 9m were converted into pentacycles 11a–e through the same methodology (Table 3

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

A cyclopeptide and three oligomycin-class polyketides produced by an underexplored actinomycete of the genus Pseudosporangium

• Shun Saito,
• Kota Atsumi,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Naoya Oku,
• Md. Rokon Ul Karim,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1100–1110, doi:10.3762/bjoc.16.97

• ' and C-1' (δC 171.1) connected C-2' and C-5' through a nitrogen atom and placed a carbonyl carbon next to C-2', establishing the Pro residue. In addition to these aliphatic portions, 14 aromatic carbons were assigned to one benzene and one indole ring by COSY and HMBC-based connectivity analysis

• correlations from aromatic protons and an indole NH proton (δH 10.70) to the aromatic carbons established the indole unit (Figure 2, Table 1). C-7'' was not bearing a proton but was connected to C-6 of the AcTyr residue based on HMBC correlations from H-6'' and H-8'' to C-6. A COSY-defined fragment C-3''/C-2

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

• -assisted cyclization and reductive elimination from the resulting σ-indolylpalladium complex C (Scheme 5). The reaction led to the stereoselective formation of indole derivatives 6ba–fc (aryl, heteroaryl and vinyl groups were allowed in substrates 5) in good to high yield. The stereochemistry of compounds

• propargylic 2-halobenzamides unsubstituted at the propargyl carbon, allowing the synthesis of isoquinolinones without substituents at C-3; but the present methodology overcame these limitations. Moreover, the previously developed strategy of indole synthesis through an aminopalladation/reductive elimination

• residue was purified by flash chromatography (silica gel, n-hexane/EtOAc, 70:30 v/v) to afford the dihydroisoquinolin-1(2H)-one 4aa. General procedure for the preparation of indole-substituted dihydroisoquinolin-1(2H)-ones 6: To a stirred solution of propargylamide 2 (0.1 mmol) in MeCN (2 mL) were added 2

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• , and Grignard reagents. Review Copper-catalysed C–C bond-forming reactions at the heterocycle The direct synthesis of chiral heterocyclic molecules from pyridine, quinolone, or indole derivatives is advantageous due to the abundance of such building blocks. Unfortunately, establishing catalytic

Synthesis of new asparagine-based glycopeptides for future scanning tunneling microscopy investigations

• Laura Sršan and
• Thomas Ziegler

Beilstein J. Org. Chem. 2020, 16, 888–894, doi:10.3762/bjoc.16.80

• is well known that Fmoc-protected tryptophane can lead to unwanted side products when the NH group in the indole ring remains unprotected, we decided to refrain from additional protection of the indole moiety because the removal of that protecting group would have reduced the overall yield in the end

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

• desired products were obtained in good to excellent yields without requiring a column chromatographic purification. The reusability of the catalytic system and large-scale synthesis of indolyl(phenyl)methanols, which would further transform into biological active indole-derived compounds, are further

• advantages of this protocol. Keywords: C–C-bond formation; C3-funtionalization of indole; diindolylmethane; Friedel–Crafts reaction; indole; indole-3-carbinol; large-scale synthesis; recyclability; Introduction (1H-Indol-3-yl)methanols have emerged as versatile pre-electrophiles for C–C functionalization

• have been used as key precursors for the construction of complex indole derivatives that would be useful in pharmaceuticals as drugs and agrochemicals [2][3][4][5][6][7][8][9][10][11][12][13][14]. The simple (1H-indol-3-yl)methanol, a breakdown product of glucobrassicin, which can be found in

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

• involved in these transformations. Keywords: cyclization; indole derivatives; oxidation; radical reaction; trifluoromethylthiolation; Introduction The trifluoromethylthio (SCF3) group could significantly improve the lipophilicity of organic molecules as shown by its high Hansch constant (π = 1.44 for

• )propioloyl]indole and N-propargylindoles, respectively. Inspired by these elegant results, we became interested in the preparation of SCF3-substituted pyrrolo[1,2-a]indol-3-ones, which might be potentially useful in medicinal chemistry. Radical cascade reactions constitute highly efficient strategies for the

• effect of the substitution on the indole ring. Both electron-donating and withdrawing groups at different positions of the indole ring produced the bis(trifluoromethylthiolated) products 2a–o in moderate to good yields. A wide range of functionalities such as alkyl, alkoxy, nitro, nitrile, ester

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• ]. It should be noted that TOI3-rev in this article is different from TOI3 in the previous reporting [12]. Here, the 1,2-diazole ring has been replaced with that of a pyrimidine core. Given the abundance of literature regarding analogues having modifications of the indole amine unit and vinylogous

• that of panobinostat [12]. In developing such analogues, the hydroxamate tails and indole capping moiety were maintained as both are essential to binding at the active site of HDAC2 and HDAC8. Results suggested that TOI1, TOI2, and TOI4 [12] would be inhibitors exhibiting similar potency as that of

• indole ring of TOI4 was also contorted upward, forming a T-shaped π–π interaction with Phe-207 while both the indole rings of TOI1 and TOI2 were shown to be flipped downward forming a T-shaped π–π interaction with Phe-208. TOI4 is the only diazine compound having two nitrogens directly next to each other

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• silacycles. For example, the intramolecular C–H silylation of biphenylhydrosilanes can be used to prepare various silafluorene derivatives [30][31][32][33][34] and the ruthenium-catalyzed intermolecular Friedel–Crafts-type reaction of 2-phenylindole with a variety of dihydrosilanes affords indole-fused

Room-temperature Pd/Ag direct arylation enabled by a radical pathway

• Amy L. Mayhugh and
• Christine K. Luscombe

Beilstein J. Org. Chem. 2020, 16, 384–390, doi:10.3762/bjoc.16.36

• goals. Room-temperature polymerization would further improve the cost and energy efficiencies required to prepare these materials. Reported herein is new mechanistic work studying the underlying mechanism of room temperature direct arylation between iodobenzene and indole. Results indicate that room

• -temperature, Pd/Ag-catalyzed direct arylation systems are radical-mediated. This is in contrast to the commonly proposed two-electron mechanisms for direct arylation and appears to extend to other substrates such as benzo[b]thiophene and pentafluorobenzene. Keywords: direct arylation; indole; palladium

• directly influences the quality and electronic performance of the material [7][9]. More specific to this work, the direct arylation method should be catalytic, directing-group free and at room temperature; a handful of such methods have been reported [10][11][12][13][14]. One such method, an indole

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

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

• 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

• amount of copper as an oxidant [109][110], this reaction was carried out under mild reaction conditions in the presence of photoredox catalyst 10 and a Rh catalyst (Scheme 7). They also reported another Pd-catalyzed indole synthesis with photoredox catalyst 9, similar to the Rh-catalyzed synthesis [108

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

• -withdrawing and electron-donating groups on the indole moiety. Additionally, a “robustness screen” has also been employed to demonstrate the tolerance of several functional groups relevant to medicinal chemistry. With respect to the Ru nanocatalyst, it has been demonstrated that it is recoverable and

• on the surface are responsible for the high catalytic efficiency of the Ru nanocatalyst. Keywords: alkenylation; C–H activation; heterogeneous catalysis; nanocatalysis; ruthenium catalysis; Introduction The synthesis of functionalised indole ring systems has received significant attention over the

• years, as these are the vital structural motifs of several biologically and medicinally important compounds [1][2][3][4]. Also, 3-alkenylindoles act as fundamental building blocks for the synthesis of materials such as carbazoles [5][6], indole alkaloids [7][8][9], etc. Again, 3-alkenylindoles also form