Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• , reduction with LiAlH4, reductive amination and allylation that afforded the indole derivatives 63 (18%) and N-Boc protected compound 68 (23%). The reaction of 63 with Pd(OAc)2 (25 mol %) and tri(o-tolyl)phosphine (55 mol %) at reflux gave 9-endo-64a (24%) and 8-exo-65b (21%). However, the compound 68 under

A new and convenient synthetic way to 2-substituted thieno[2,3-b]indoles

• Roman A. Irgashev,
• Arseny A. Karmatsky,
• Gennady L. Rusinov and
• Valery N. Charushin

Beilstein J. Org. Chem. 2015, 11, 1000–1007, doi:10.3762/bjoc.11.112

• attention of researchers, mainly due to the fact that thieno[2,3-b]indole derivatives exhibit a wide range of biological properties, and can be regarded as promising compounds for agricultural or pharmacological applications. For example, the alkaloid thienodolin [1], isolated from the fermentation mixture

• (method B), when compounds 10 failed to be obtained by method A (Table 1, Scheme 4). It should be noted that thieno[2,3-b]indole derivatives 12e,f bearing 4-CN- or 2-NO2-phenyl substituents at C-2 have been prepared in high yields from the appropriate indolin-2-ones 10e,f by treatment with Lawesson’s

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• indole derivatives. Anodic anellation of catechol derivatives 66 with different 1,3-dicarbonyl compounds. Electrosynthesis of 1,2-fused indoles from catechol and ketene N,O-acetals. Reaction of N-acyliminium pools with olefins having a nucleophilic substituent. Synthesis of thiochromans using the cation

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• convenient method for the synthesis of 2-(trifluoromethyl)indoles by introducing the trifluoroacetyl group to activate the CuI/L-proline-catalyzed system [21]. Zhao [22] and Kobayashi [23] reported the synthesis of 2-amino-1H-indole derivatives using the same kind of copper-catalyzed system. Meanwhile, the

• domino cyclization. Based on the previous work for the copper-catalyzed synthesis of 2-amino-1H-indole derivatives and copper-catalyzed N-arylation, we herein report a simple and efficient one-pot method to synthesize indolo[1,2-a]quinazolines by a sequential Ullmann-type C–C and C–N coupling. Compared

A new approach for the synthesis of bisindoles through AgOTf as catalyst

• Jorge Beltrá,
• M. Concepción Gimeno and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2014, 10, 2206–2214, doi:10.3762/bjoc.10.228

• considerable attention over the past decades, the development of new synthetic [4][5] and catalytic [6][7][8][9][10][11] methods leading to functionalized indole derivatives is still an active field because their application in drug discovery [12][13][14]. Indole is the structural core unit of

• bisindolylmethane derivatives (BIMs), many of them isolated from marine natural sources [15][16] and are an important class of indole derivatives which exhibit an appealing range of biological properties such as antibacterial, antifungal, antimicrobial or anti-inflammatory, among others (Figure 1) [17

• program focused on the synthesis of new indole derivatives, we centered our attention in the preparation of bisindolylmethane derivatives following a very easy and straightforward procedure, in order to contribute to the development of this field. Accordingly, we decided to evaluate the possibility of

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• route through compound 5 to be higher yielding (route E). This is an interesting finding since the preparation of 1,2-diarylindoles via initial N-arylation is rarely reported. Independent of the final reaction step towards 1 it is already obvious that a strategy starting from indole derivatives 2 via

Aminofluorination of 2-alkynylanilines: a Au-catalyzed entry to fluorinated indoles

• Antonio Arcadi,
• Emanuela Pietropaolo,
• Antonello Alvino and
• Véronique Michelet

Beilstein J. Org. Chem. 2014, 10, 449–458, doi:10.3762/bjoc.10.42

• to C-3 fluorinated indole derivatives was less investigated. Fluorination of trialkylstannylindole derivatives with cesium fluoroxysulfate or Selectfluor was investigated for the synthesis of the corresponding 3-fluoroindoles [17]. A borane–tetrahydrofuran complex has been used to study the reduction

• was difluorinated highly regioselectively at the C-3 carbon site with Selectfluor [20]. The C-3 monofluorinated indole derivatives were supposed to serve as intermediates in the transformation and can be isolated under suitable reaction conditions [21]. We envisaged that the aminofluorination of the

Synthesis of indole-based propellane derivatives via Weiss–Cook condensation, Fischer indole cyclization, and ring-closing metathesis as key steps

• Sambasivarao Kotha,
• Ajay Kumar Chinnam and
• Arti Tiwari

Beilstein J. Org. Chem. 2013, 9, 2709–2714, doi:10.3762/bjoc.9.307

• propellane derivatives involves a Weiss–Cook condensation, a Fischer indole cyclization, and a ring-closing metathesis as key steps. Keywords: allylation; indole derivatives; propellanes; ring-closing metathesis; Weiss–Cook condensation; Introduction Propellanes are tricyclic systems conjoined with carbon

• diversification: (i) various aryl and heteroaryl fused indole derivatives can be assembled by choosing an appropriate hydrazine derivative, (ii) during the alkylation of diketone 2 [43] various unsaturated alkenyl fragments may be incorporated either in a symmetrical or in an unsymmetrical manner, (iii) various

• to indole-based propellane 4. Preparation of diindole dione 2. Synthesis of allylated indole derivatives 3, 7 and 8. Synthesis of indole-based propellane derivatives 4 and 11 by RCM route. Synthesis of 4 by Weiss–Cook condensation and two fold Fischer indole cyclization. Supporting Information

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• , this issue does not preclude the development of enantioselective variants, provided the initial fluorination event can be controlled [11]. Gouverneur and co-workers recently reported the first enantioselective electrophilic fluorocyclisation (Scheme 8) [71]. Their substrates (e.g. 69) were indole

• derivatives bearing a pendant nitrogen nucleophile, and the source of chirality was a substoichiometric quantity of the cinchona alkaloid derivative (DHQ)2PHAL (70). This method was shown to work very well with several different pendant nucleophiles, but the N-acetamido nucleophile was found to be optimal

Organocatalytic asymmetric selenofunctionalization of tryptamine for the synthesis of hexahydropyrrolo[2,3-b]indole derivatives

• Qiang Wei,
• Ya-Yi Wang,
• Yu-Liu Du and
• Liu-Zhu Gong

Beilstein J. Org. Chem. 2013, 9, 1559–1564, doi:10.3762/bjoc.9.177

• tryptamine derivatives provides access to 3a-(phenylselenyl)-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole derivatives in high yields and with synthetically useful levels of enantioselectivity (up to 89% ee). Keywords: catalysis; chiral phosphoric acid; hexahydropyrrolo[2,3-b]indole; indole alkaloids; natural

Simple synthesis of pyrrolo[3,2-e]indole-1-carbonitriles

• Adam Trawczyński,
• Robert Bujok,
• Zbigniew Wróbel and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2013, 9, 934–941, doi:10.3762/bjoc.9.107

• -dihydropyrrolo[3,2-e]indole fragment is present in anticancer agents, such as CC-1065 [1], duocarmycin [1], and yatakemycin [2]. Some pyrrolo[3,2-e]indole derivatives show antimicrobial activity [3]. One method of synthesis of the 1,2-dihydropyrrolo[2,3-e]indoles is reduction of pyrrolo[3,2-e]indoles with sodium

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• outcome of the cyclization differs. While allylic ethers are relatively poor substrates that undergo a side elimination and need an intracyclic double bond to proceed, allylic amines react well and afford indoline and indole derivatives. Finally, the synthesis of the trinuclear ACE core of a morphine-like

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• synthesis of (±)-matrine (43). Synthesis of complex tetralones. Synthesis of functionalised azaindoline and indole derivatives. Synthesis of thiochromanones. Synthesis of complex benzothiepinones. Conditions: 1) CF3COOH; 2) RCHO / AcOH (PMB = p-methoxybenzyl). Formation and capture of a cyclic nitrone

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• the epoxide, and intramolecular Huisgen azide–internal alkyne 1,3-dipolar cycloaddition reaction, led to the generation of the diazepine and triazole rings annulated to the indole through the formation of four new sigma bonds in a single step. One-pot three-component domino reaction furnishing indole

• derivatives (4a and 5a) and indolodiazepinotriazole 6a. Transformation of intermediates 4a and 5a to 6a. Three-component domino reaction for the synthesis of tetracyclic indolodiazepinotriazole compounds based on 6a. Reaction conditions: 1a (1.0 mmol), 2 (1.1 mmol), 3 (1.5 mmol) and Cs2CO3 (1.5 mmol) in DMSO

Tandem aldehyde–alkyne–amine coupling/cycloisomerization: A new synthesis of coumarins

• Maddi Sridhar Reddy,
• Nuligonda Thirupathi and
• Madala Haribabu

Beilstein J. Org. Chem. 2013, 9, 180–184, doi:10.3762/bjoc.9.21

• product, this may result in an interesting reaction sequence to produce various heterocycles. Recently, Gevorgyan and co-workers [23] used these two processes (A3/5-exo-dig cycloisomerization) in tandem to obtain indolines, which were then converted to useful substituted indole derivatives (Scheme 1, (a

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• 10.3762/bjoc.8.198 Abstract This review highlights the development of palladium-catalyzed C–H and N–H functionalization reactions involving indole derivatives. These procedures require unactivated starting materials and are respectful of the basic principle of sustainable chemistry tied to atom economy

• ][42]. This review highlights methodologies based on the use of palladium catalysts, devoted to the functionalization of indole derivatives involving carbon–hydrogen and nitrogen–hydrogen bonds. The synthetic procedures are classified as intermolecular and intramolecular alkenylations, arylations, and

• . Although better yields were obtained with electron-donating groups, this synthetic approach tolerates a range of substituents on the indole ring. In 2010, our group disclosed a general route towards 3-vinylimidazo[1,5-a]indole derivatives 40 by the unusual and atom-economical intramolecular Pd-catalyzed

C2-Alkylation of N-pyrimidylindole with vinylsilane via cobalt-catalyzed C–H bond activation

• Zhenhua Ding and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2012, 8, 1536–1542, doi:10.3762/bjoc.8.174

• efficient and regioselective functionalization of indole derivatives [4][5][6]. Over the past decade, transition-metal-catalyzed direct functionalization has emerged as a powerful strategy for the direct introduction of aryl and alkenyl groups to the C2 and C3 positions of indole [7][8][9]. The situation is

Asymmetric one-pot sequential Friedel–Crafts-type alkylation and α-oxyamination catalyzed by a peptide and an enzyme

• Kengo Akagawa,
• Ryota Umezawa and
• Kazuaki Kudo

Beilstein J. Org. Chem. 2012, 8, 1333–1337, doi:10.3762/bjoc.8.152

• -functionalized indole or pyrrole derivatives in a highly enantioselective manner. Keywords: Friedel–Crafts-type alkylation; laccase; one-pot reaction; organocatalysis; α-oxyamination; resin-supported peptide catalyst; Findings Indole derivatives represent a class of biologically active compounds [1][2][3], and

• they often have chiral carbon chains attached to indole rings. A Friedel–Crafts-type asymmetric alkylation (FCAA) to indoles is a versatile method for synthesizing such chiral indole derivatives. To date, a number of FCAA reactions by either metal catalysts or organocatalysts have been reported [4][5

• followed by oxygenation at the α-position of the carbonyl group. If such a sequence can be realized in a one-pot reaction, it would be a powerful method for the synthesis of oxy-functionalized indole derivatives with operational simplicity. To date, there has been no report on the FCAA reaction combined

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• indole derivatives have been reported because they occur in numerous natural products and bioactive compounds. Among these different strategies, those involving a palladium-catalyzed coupling reaction have received much attention [25] and one of the most commonly used procedures involves a one-pot two

• , and the best results were obtained when Pd/C–PPh3 was used as the catalyst system (Scheme 22). Another attractive palladium-mediated multicomponent approach towards the synthesis of indole derivatives involving the cyclization of a 2-alkynylaniline intermediate is based on a sequential, site-selective

• coupling of aryl chlorides. This was followed by an intramolecular alkyne–hydroamination (addition of an N–H bond across a carbon–carbon multiple bond) leading to the corresponding indole derivatives 52. The amination/alkyne–hydroamination sequence requires the addition of 1.5 equiv of t-BuOK to reach

Solvent- and ligand-induced switch of selectivity in gold(I)-catalyzed tandem reactions of 3-propargylindoles

• Estela Álvarez,
• Delia Miguel,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez,
• Félix Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 786–793, doi:10.3762/bjoc.7.89

• -indole migration in 3-propargylindoles. Results and Discussion It is an intriguing possibility that the aura-Nazarov reaction may also take place with substrates bearing aromatic substituents at both the propargylic and terminal positions, and thus allow access to new functionalized indole derivatives

• almost exclusively to the formation of iso-Nazarov products 3 [13][14]. For instance, indoles 1j and 1k, bearing a methyl and a phenyl group at C-2, respectively, provided the corresponding indole derivatives 3j and 3k with high selectivity when the reaction was conducted in CH2Cl2 with (Ph3P)AuCl/AgSbF6

• favored the Nazarov pathway: Approximately 3/1 ratios of the corresponding indole derivatives 3l, m/4l, m were obtained (Scheme 4) [32]. In addition, we were able to isolate the new Nazarov compounds 4l and 4m, albeit in low yields (Scheme 4). Finally, when the more sterically demanding isopropyl group

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• . The wide range of alkene substrates and the low catalyst amounts render this method a highly efficient and convenient synthesis of 3-functionalized indole derivatives (Scheme 19). An elegant PtCl2-catalyzed intramolecular alkylation of indoles with inactivated alkenes has been developed by Widenhoefer

An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

• Rajeshwar Reddy Sagyam,
• Ravinder Buchikonda,
• Jaya Prakash Pitta,
• Himabindu Vurimidi,
• Pratap Reddy Padi and
• Mahesh Reddy Ghanta

Beilstein J. Org. Chem. 2009, 5, No. 66, doi:10.3762/bjoc.5.66

•  1) was synthesized in 21% yield from 1-aminopyrrole and 3-ethoxyacrolein diethylacetal [26]. As a part of our continued interest in the development of new synthetic methods for highly substituted pyrrole and indole derivatives [27][28], we have developed a new synthetic route to pyrrolo[1,2-b

Pd/C- Mediated synthesis of indoles in water

• Mohosin Layek,
• Udaya Lakshmi,
• Dipak Kalita,
• Deepak K. Barange,
• Aminul Islam,
• K. Mukkanti and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 46, doi:10.3762/bjoc.5.46

• -catalyzed reactions in aqueous media, we have reported an efficient synthesis of 2-substituted indoles via a Pd/C-catalyzed coupling-cyclization process in water [14]. Herein, we report a further continuation of our previous work towards the synthesis of a variety of indole derivatives along with the

• N-substituted indole derivatives successfully we then undertook the synthesis of the target indole C. Compound C was prepared from bromo compound 4 following a 7-step process using the Pd/C-mediated indole synthesis as a key step as shown in Scheme 2. Thus treatment of bromide 4 with Na2SO3 provided

• . Conclusions In conclusion, we have demonstrated the potential of our previously reported palladium on carbon mediated practical synthesis of 2-substituted indoles in water. Besides preparing a wide variety of indole derivatives the methodology was utilized to prepare one of our target indole derivatives

Novel base catalysed rearrangement of sultone oximes to 1,2-benzisoxazole- 3-methane sulfonate derivatives

• Veera Reddy Arava,
• Udaya Bhaskara Rao Siripalli,
• Vaishali Nadkarni and
• Rajendiran Chinnapillai

Beilstein J. Org. Chem. 2007, 3, No. 20, doi:10.1186/1860-5397-3-20

• activities and are useful in different therapies. The 1,2-benzisoxazole moieties are isosteric with indoles and can mimic/bind to biologically important enzymes in a manner similar to indole derivatives. Out of many biologically active compounds, zonisamide is widely prescribed as an anti-epileptic drug. It