Atom-economical group-transfer reactions with hypervalent iodine compounds

• Andreas Boelke,
• Peter Finkbeiner and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2018, 14, 1263–1280, doi:10.3762/bjoc.14.108

• ]. A selective C–H arylation at C3 of the indole was realised under copper catalysis before the addition of a ligand and an inorganic base initiated the N-arylation with the in situ formed iodoarene. The desired diarylated indoles 11 are obtained with an AE of 46% (for R1 = R2 = H, Ar1 = Ar2 = Ph). The

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• heteroarenes was realized using the benziodoxolone hypervalent iodine reagents indoleBXs. Functionalization of the C–H bond in bipyridinones and quinoline N-oxides catalyzed by a rhodium complex allowed to incorporate indole rings into aza-heteroaromatic compounds. These new transformations displayed complete

• -pyridinone ring is present in milrinone (1), used to treat heart failure, while a 4-pyridinone is part of mimosine (2), an alkaloid isolated from Mimosa pudica. A benzene-fused pyridinone – a quinolone – can be found in brexpiprazole (3), a drug used against schizophrenia. In addition, the indole core is

• transformations [22], but only one application of indole iodonium salts in copper catalysis by You and co-workers had been reported until 2017 [23]. In this context, indole-based benziodoxole hypervalent iodine reagents, recently introduced by Yoshikai's and our group [24][25][26][27], appeared ideal partners to

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• active natural tropone fused to indole rings (Figure 1). Benzo-annulated cycloheptanones (as colchicine [8], allocolchicine), benzo[7]annulenones, or benzotropones (as purpurogallin) and their analogues are present in a great variety of pharmacologically relevant natural products [27][28][29]. Colchicine

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• conjugates form layer-like structures during crystal formation via multiple hydrogen bonding interactions. This structural information indeed helps to design novel MGBs with much better binding affinity and specificity. A new family of conjugates between a Zn(II)-tach complex and (indole)2 or benzofuran

• –indole amide minor groove binders connected through alkyl or ethoxyethyl linkers were developed by Tecilla et al. [111]. The authors confirmed that these conjugates with tach units, either free or Zn(II)-complexed forms, bind strongly to the minor groove through electrostatic interactions with the

Volatiles from the xylarialean fungus Hypoxylon invadens

• Jeroen S. Dickschat,
• Tao Wang and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

• 2-phenylethanol (10), and the trace components acetophenone (9), terpinen-4-ol (13), and indole (16). For several other compounds in the headspace extract close hits for highly substituted aromatic compounds were found in our mass spectral libraries, but the mass spectra and retention indices for

Mannich base-connected syntheses mediated by ortho-quinone methides

• Petra Barta,
• Ferenc Fülöp and
• István Szatmári

Beilstein J. Org. Chem. 2018, 14, 560–575, doi:10.3762/bjoc.14.43

• -1H-indole in the presence of lithium perchlorate as catalyst to afford the new 3,3-dimethyl-2,3,4,9-tetrahydro-1H-xanthen-1-ones and 3-substituted indoles. The process was then extended to isocyanides and new aminobenzofurans formed via [4 + 1] cycloaddition were isolated. Bharate et al. reported

• indole polyheterocycles 49 and 50 in good yields with 90–99% ee. One of the latest publications around this topic has been reported by Deb et al. [86][87]. Various 2-(aminoalkyl)phenols or 1-(aminoalkyl)naphthols 51 were reacted with indoles under Brønsted acid catalysis resulting in 3-(α,α-diarylmethyl

• )indoles 52. Then, through C-2 cyclization of the indole ring using I2 as catalyst and tert-butyl hydroperoxide as oxidant, chromeno[2,3-b]indoles were isolated in 71–98% yields. In a different reaction pathway, starting from 3-(aminoalkyl)indoles 53 and phenols or naphthols, 3-(α,α-diarylmethyl)indoles 52

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -irradiated reaction of 5-aminopyrazoles 16, 2,2-dihydroxy-1-phenylethanone (98) and p-toluidine (99) under various polar and non-polar solvents with bronsted and lewis acid catalysts (Scheme 29). The reaction in dimethylformamide in presence of p-TSA resulted in the formation of azepino[5,4,3-cd]indole 100

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

• carbanions and nitroarenes, to indolo[3,2-b]quinoline derivatives. As starting nucleophile precursors, we have chosen derivatives of indole-2-ylmethyl phenyl sulfone (1a), tert-butyl indol-2-ylacetate (1b,c) and indol-2-ylacetonitrile (1d). As a model compound for screening of the reaction conditions, we

• 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

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• conditions and Cu(OH)2 and Ag2CO3 were the best catalyst and oxidant, respectively. The electron density of the pyrrole ring had impact on the efficiency. N-Tosylindole and indole bearing the CO2Me group on C3 position were nearly unreactive. A plausible mechanism was proposed based on preliminary

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

• 1O2 is generated by photoexcited Rose Bengal via energy transfer and abstracts a hydrogen atom from the aryl thiol. Radical addition on the indole derivative, oxidation and rearomatization via deprotonation yields the corresponding sulfenylated indole derivative. Very recently, Wei, Wang and co

• 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

• the indole, to the respective cation. Deprotonation yields the desired thiocyanated indole derivative. One year later, the group of Hajra reported a similar approach for the thiocyanation of imidazoheterocycles, applying Eosin Y as photoredox catalyst under aerobic conditions (Scheme 26) [61]. The

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

• to be interesting substrates for cascade reactions, allowing to obtain the 3-trifluoromethylated indole 39 albeit in low yield (Scheme 31) [40]. Chlorotrifluoromethylation of alkynes: In the continuity of their work on alkenes, Jung and Han got interested in the chlorotrifluoromethylation of internal

• , 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

• trifluoromethylsulfenylated analogue (Scheme 33). Yi and co-workers reported that the reaction could also be performed in acetonitrile at 90 °C, with diethyl phosphite as the reducing agent (Scheme 34) [43]. These modifications allowed to get improved yields for the trifluoromethylsulfenylation of indole and pyrrole

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• -tetramethylpiperidine 1-oxyl), the detection of Ag(0) by X-ray photoelectron spectroscopy, the retardation of the reaction in absence of air and an 18O-labeling reaction led the authors to propose the mechanism described in Scheme 4 [23]. Because some limitations appeared with heterocycles such as quinolone, indole

• (Scheme 11) [30]. Amino- and azotrifluoromethylation of alkenes: Alkene trifluoromethylation was applied to the construction of indole, pyrazole and pyridazinone moieties via a multicomponent cascade reaction developed by Antonchick and Matcha in 2014 [31]. The method was based on the reaction between

• stoichiometric amounts of oxidant and further transformation of the azotrifluoromethyl products allowed a Fisher indole synthesis. From a mechanistic point of view, the excited photocatalyst was oxidised by the aryldiazonium salt to produce [Ru(bpy)3]3+ (bpy: 2,2’-bipyridine) as the oxidant to generate the CF3

Synthesis of 1,3-cis-disubstituted sterically encumbered imidazolidinone organocatalysts

• Jan Wallbaum and
• Daniel B. Werz

Beilstein J. Org. Chem. 2017, 13, 2577–2583, doi:10.3762/bjoc.13.254

• -tryptophan-derived methyl amides 9b and 9c were converted in good yields to the corresponding imidazolidinones (Table 1, entries 2 and 3). In the case of 7c it is important to use not more than 1.0 equivalent of the aldehyde, otherwise a further reaction with the indole moiety is observed. A significant

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• chemistry; heterocycle; hydrogenation; indole; multistep; Introduction Indoles are amongst the most important bioactive heterocyclic structures being commonly encountered in the amino acid tryptophan (1), the related neurotransmitter serotonin (2) as well as numerous complex alkaloid natural products and

• pharmaceuticals [1][2][3][4]. Indoles also play a significant role as phytohormones that promote and regulate the growth and development of plants. Indeed, four of the five endogenously synthesised auxins produced by plants contain the indole motif (Figure 1, structures 3–7). As a consequence of their regulatory

• activity these structures have become prime targets for investigations into both enhancing plant growth as well as targeted plant growth inhibition generating new agrochemical herbicides [5]. A recent collaboration investigating the uptake and resulting distribution of synthetic indole-3-acetic acid

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

• , Japan Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan 10.3762/bjoc.13.226 Abstract The parent benzophospholo[3,2-b]indole was prepared by the reaction of dichlorophenylphosphine with a dilithium intermediate, which was prepared in two steps from 2-ethynyl-N,N

• -dimethylaniline. Using the obtained benzophosphole-fused indole as a common starting material, simple modifications were carried out at the phosphorus center of the phosphole, synthesizing various functionalized analogs. The X-ray structure analysis of trivalent phosphole and phosphine oxide showed that the fused

• tetracyclic moieties are planar. The benzophosphole-fused indoles, such as phosphine oxide, phospholium salt, and borane complex, exhibited strong photoluminescence in dichloromethane (Φ = 67–75%). Keywords: benzophospholo[3,2-b]indole; DFT calculation; molecular structure; phosphole derivatives

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• syntheses of alstilobanines A, E and angustilodine, functionalized indole 33 was initially chosen as a key intermediate [33]. However, attempts of its preparation by Michael addition of substituted indole enolate 34 to nitrosoalkene NSA8, generated in situ either from the corresponding chlorooxime 35 or its

• TBS ether 36 failed (Scheme 13). The problem was elegantly solved by using indole dianion 37 as both a nucleophile and a base. Reaction of 37 with α-chlorooxime 35 required only one equivalent of nucleophile and produced adduct 38 in 99% yield. Oxime 38 was transformed into a pentacyclic derivative 39

• , which served as a direct precursor of target alkaloids alstilobanines A, E and angustilodine. The same strategy was employed to construct the tetracyclic core of the apparicine class of indole alkaloids (see Scheme 14) [36]. Here, coupling of indole dianion 40 with chlorooxime 35 (via nitrosoalkene NSA8

Regiodivergent condensation of 5-alkoxycarbonyl-1H-pyrrol-2,3-diones with cyclic ketazinones en route to spirocyclic scaffolds

• Alexey Yu. Dubovtsev,
• Maksim V. Dmitriev,
• Аndrey N. Maslivets and
• Michael Rubin

Beilstein J. Org. Chem. 2017, 13, 2179–2185, doi:10.3762/bjoc.13.218

• between two alternative directions affording derivatives of partially hydrogenated indole or benzofurane. The control of this regioselectivity is efficiently governed by steric effects at the hydrazone moiety of the ketazinone reagent. Keywords: nitrogen heterocycles; oxygen heterocycles; pyrrolediones

• ; spiro compounds; synthetic methods; Introduction Molecular structures based on partially or exhaustively hydrogenated indole and benzofuran cores are omnipresent in nature. Both types of ring systems are found in a variety of important biologically active natural products [1][2][3][4][5][6][7][8][9][10

• in the target-oriented synthesis of pyrrole-based natural alkaloids [34][35][36][37][38]. Herein we wish to report a new synthetic route towards spirocyclic scaffolds possessing partially hydrogenated indole or benzofuran cores. The featured approach is based on the highly efficient regiodivergent

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• formation of a 2,3-diarylindole was observed under the same conditions. Keywords: arylation; fused-ring systems; indole formation; palladium catalysis; sultams; Introduction The sulfonamide functional group stands out as one of the most important pharmacophores. At the same time, cyclic sulfonamides

• susceptible to very rapid oxidation upon work-up in air to give the corresponding indole 18. In order to test the applicability of the palladium-catalyzed intramolecular arylation of a sulfonamide with a C–H acidic group for the preparation of benzannelated six-membered sultams like 21, the appropriate

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

• developed a mechanochemical synthesis of an indole moiety via a Rh-catalyzed C–H functionalization strategy under planetary ball mill [187]. Using acetanilide and diphenylacetylene as the alkyne component in presence of 5 mol % Rh catalyst and 2.5 mol % Cu(OAc)2 and 1 atm O2 as terminal oxidant they could

• 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

• particles [146]. Mechanochemical synthesis of 1,2-di-substituted benzimidazoles [149]. Mechanochemical click reaction using an alumina-supported Cu-catalyst [152]. Mechanochemical click reaction using copper vial [155]. Mechanochemical indole synthesis [157]. Mechanochemical synthesis of chromene [158

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• byproduct. The formation of the 4-hydroxy-THIQs vs the 4-methoxy-THIQ products could be controlled through modification of the reaction concentration. In addition, while a highly-activated system exclusively cyclized to the indole, this seems generally highly disfavored. When competition between 6- and 7

• , compounds bearing a different number of methoxy groups were selected in order to understand the electronic constrains that might render indole formation competitive. Upon treatment with 70% HClO4, acetals 9a and 9o yielded the respective THIQs 10a and 10o. However, the highly-activated acetal 9p exclusively

• cyclized into the indole 16p. It is thus possible to infer that indole formation is highly disfavored and only the presence of a great number of activating groups can make this outcome competitive. We then decided to expand our analysis to include competition between 6- and 7-membered ring formation

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

• proceeds via base-promoted propargyl–allenyl rearrangement followed by cyclization and allyl migration. Phosphine-substituted indoles can be synthesized by a similar strategy. Keywords: allyl migration; benzothiophene; indole; metal-free; propargyl-allenyl; Introduction Heterocycles are frequently found

• 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

• , which were versatile synthetic intermediates [37][38]. The N-methyl-N-allylpropargyl alcohol 3 was treated with (EtO)2PCl under alkaline conditions, then underwent a propargyl phosphite/allenyl phosphonate rearrangement and an intramolecular nucleophilic attack to form the indole moiety, followed by

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• dehydrogenation of C–C and C–N bonds utilizing metal catalysts with synthetic oxidants. The first example is illustrated by transforming an indoline to an indole [91]. In general, indoles are one of the most popular moieties that are observed in a plethora of bioactive natural products and active pharmaceutical

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• benzene ring protons (H3, H4, H5 and H6) indicate a 1:1 host/guest stoichiometry, whereas those of the indole moiety (H8) and of the aliphatic protons (H9,9’, H10, H12), with an inflection point at ≈0.3, suggest a host/guest ratio close to 2:1. This behavior reveals the existence of two different

• complexation modes, one involving the indole phenyl ring with one host only and the aliphatic chain with two host molecules. The fact that the second mode takes place mainly when there is an excess of host concentration indicates that the inclusion of the indole moiety is the predominant mode of interaction

• were obtained under identical conditions (temperature, concentration, acquisition parameters). Strong intermolecular dipolar interactions were observed between indole protons (H3, H4, H5, H6, H8) and the β-CD cavity protons (H5, H6,6’, H3) in both enantiomeric guests, confirming full inclusion of the

1-Imidoalkylphosphonium salts with modulated C_α–P⁺ bond strength: synthesis and application as new active α-imidoalkylating agents

• Jakub Adamek,
• Roman Mazurkiewicz,
• Anna Węgrzyk and
• Karol Erfurt

Beilstein J. Org. Chem. 2017, 13, 1446–1455, doi:10.3762/bjoc.13.142

• aromatic systems with strong electron-donating substituents (e.g., alkoxy-, polyalkoxy- and aminoarenes), or some activated heterocyclic systems such as indole [3][8][10][24][25]. The α-imidoalkylation reaction using N-(1-hydroxyalkyl)imides (almost entirely N-hydroxymethylphthalimide) in sulfuric acid

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• non-classical inputs for the Joullié–Ugi reaction and for subsequent preparation [28] of sterically encumbered, constrained peptidomimetic frameworks. Diversely substituted indolenines 9 are easy to prepare via the Fischer indole synthesis [26] and their use in the CCR can be expected to result in