Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• to both the electronics of the arene and the nucleophilicity of the amine. Particularly electron-rich arenes such as N-methylindole are not tolerated, as is the case for relatively nucleophilic amines such as imidazoles, anilines or alkylamines. The reported substrates are particularly valuable to

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• was elaborated for the naked-eye detection of ADP with a detection limit of 0.5 mM. Keywords: ADP; amphiphile; ATP; calix[4]arene; CuAAC; eosin Y probe; molecular recognition; polydiacetylene; self-assembly; triazole; Introduction During the last two decades many researcher groups have paid much

• the p-tert-butylthiacalix[4]arene platform with 1,3-alternate conformation having polyammonium binding sites. They were shown to effectively interact with calf thymus DNA causing a 4-fold compaction of the latter [25]. Related macrocycles containing two cationic imidazolium fragments demonstrated a

• high affinity to ATP [26]. Herein we report the synthesis of new amphiphilic water-soluble calix[4]arene derivatives with cone conformation containing two or four polyammonium groups on the upper rim by using a click chemistry approach and the results of binding studies toward nucleotides in aqueous

An amphiphilic pseudo[1]catenane: neutral guest-induced clouding point change

• Tomoki Ogoshi,
• Tomohiro Akutsu and
• Tada-aki Yamagishi

Beilstein J. Org. Chem. 2018, 14, 1937–1943, doi:10.3762/bjoc.14.167

• /hydrophilic ratio in a molecule largely affects its assembled properties in aqueous media. In this study, we synthesized a new bicyclic compound which could dynamically change its hydrophobic/hydrophilic ratio by chemical stimulus. The bicyclic compound consisted of amphiphilic pillar[5]arene and hydrophobic

• alkyl chain rings, and formed a self-inclusion structure in aqueous media, which was assigned as a pseudo[1]catenane structure. The hydrophobic chain ring was hidden inside the pillar[5]arene cavity in the pseudo[1]catenane structure, thus the bicyclic compound was soluble in water at 20 °C with a

• –guest chemistry [5][6][7]. The molecules consist of a non-ionic amphiphilic part containing tri(ethylene oxide) moieties, and a hydrophobic part consisting of a pillar[n]arene core (Figure 1a; 1, n = 5; 2, n = 6). Pillar[n]arenes, which were first reported by our group [11], were used as the macrocyclic

Asymmetric Michael addition reactions catalyzed by calix[4]thiourea cyclohexanediamine derivatives

• Zheng-Yi Li,
• Hong-Xiao Tong,
• Yuan Chen,
• Hong-Kui Su,
• Tangxin Xiao,
• Xiao-Qiang Sun and
• Leyong Wang

Beilstein J. Org. Chem. 2018, 14, 1901–1907, doi:10.3762/bjoc.14.164

• clearly showed that the upper rim-functionalized hydrophobic calixarene scaffold played an important role in cooperation with the catalytic center to the good reactivities and enantioselectivities. Keywords: asymmetric Michael addition reaction; calix[4]arene; cyclohexanediamine; thiourea; Introduction

• hydrophobic cavity and chiral sites during a catalytic process [24][25]. Recently, we have reported a series of different functionalized organic catalysts based on calixarenes [26][34][35][36][37][38]. For example, we have been developed a calix[4]arene-based L-proline catalyst able to catalyze aldol

• Michael addition reactions of acetylacetone and aromatic nitroalkenes. Results and Discussion Synthesis of catalysts The chemical structures and synthetic pathways for catalysts are shown in Scheme 1 and Scheme 2, respectively. A series of upper rim-functionalized calix[4]arene-based cyclohexanediamine

Strong binding and fluorescence sensing of bisphosphonates by guanidinium-modified calix[5]arene

• Jie Gao,
• Zhe Zheng,
• Lin Shi,
• Si-Qi Wu,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2018, 14, 1840–1845, doi:10.3762/bjoc.14.157

• diseases. Guanidinium-modified calix[5]arene (GC5A) affords strong binding on the micromolar to nanomolar level towards BPs dominantly via multiple salt bridge interactions, which was evaluated by fluorescence competitive titrations. Fluorescent IDA enables the highly sensitive and label-free detection of

• ]arene (GC5A, Scheme 1b). Such label-free sensing strategy exhibits potential application in real-time monitoring concentrations of BPs in urine and pharmacokinetic studies. Results and Discussion The main skeleton of BPs possesses two phosphate groups which are potential binding sites and therefore GC5A

• etidronate in (a) HEPES buffer (10 mM, pH 7.4) and (b) artificial urine at 25 °C. Error bars could not be shown if less than 0.005. The chemical structures of (a) bisphosphonates (BPs) and (b) guanidinium-modified calix[5]arene (GC5A). (c) Schematic illustration of a salt-bridge between a phosphate anion and

Synthesis and photophysical studies of a multivalent photoreactive Ru^II-calix[4]arene complex bearing RGD-containing cyclopentapeptides

• Sofia Kajouj,
• Lionel Marcelis,
• Alice Mattiuzzi,
• Adrien Grassin,
• Damien Dufour,
• Pierre Van Antwerpen,
• Didier Boturyn,
• Eric Defrancq,
• Mathieu Surin,
• Julien De Winter,
• Pascal Gerbaux,
• Ivan Jabin and
• Cécile Moucheron

Beilstein J. Org. Chem. 2018, 14, 1758–1768, doi:10.3762/bjoc.14.150

• is also faced by complexes anchored on cell-penetrating peptides. In order to provide a selective cell targeting, we developed a multivalent system composed of a photoreactive ruthenium(II) complex tethered to a calix[4]arene platform bearing multiple RGD-containing cyclopentapeptides. Extensive

• target cancerous cells, we envisaged to graft a photoreactive RuII complex on a multivalent platform decorated with multiple RGD-containing cyclopentapeptides. A calix[4]arene moiety was chosen as the multivalent platform as this rigid macrocycle displays two distinct faces that can be selectively

• functionalized [54][55][56]. It is noteworthy that the calix[4]arene skeleton has been already exploited for the development of multivalent glyco- and peptidocalixarenes that can be recognized by cell-membrane receptors [57][58][59] and of calixarene derivatives able to specifically target membrane proteins

Synthesis of diamido-bridged bis-pillar[5]arenes and tris-pillar[5]arenes for construction of unique [1]rotaxanes and bis-[1]rotaxanes

• Ying Han,
• Li-Ming Xu,
• Cui-Yun Nie,
• Shuo Jiang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2018, 14, 1660–1667, doi:10.3762/bjoc.14.142

• Ying Han Li-Ming Xu Cui-Yun Nie Shuo Jiang Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, P. R. China 10.3762/bjoc.14.142 Abstract The pillar[5]arene mono- and di(oxyalkoxy)benzoic acids were successfully prepared in high yields by

• sequential alkylation of ω-bromoalkoxy-substituted pillar[5]arenes with methyl or ethyl p-hydroxybenzoate followed by a hydrolytic reaction under basic conditions. Under catalysis of HOBt/EDCl, the amidation reaction of pillar[5]arene mono(oxybutoxy)benzoic acid with monoamido-functionalized pillar[5]arenes

• afforded diamido-bridged bis-pillar[5]arenes. 1H NMR and 2D NOESY spectra clearly indicated that [1]rotaxanes were formed by insertion of longer diaminoalkylene unit into the cavity of one pillar[5]arene with another pillar[5]arene acting as a stopper. The similar catalysed amidation reaction of pillar[5

Direct electrochemical generation of organic carbonates by dehydrogenative coupling

• Tile Gieshoff,
• Vinh Trieu,
• Jan Heijl and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2018, 14, 1578–1582, doi:10.3762/bjoc.14.135

• material could be isolated. We assumed that the presence of different aromatic positions lowered the selectivity of the reaction. We changed to mesitylene as the arene, since it exhibits equivalent aromatic positions for carbonate functionalization. This approach enabled a selective process and led to

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• changes are rare. In this article, we present a thorough study on the host–guest chemistry of a conformationally adaptive macrocycle, namely per-O-ethoxyzorb[4]arene (ZB4). Similar to per-O-ethoxyoxatub[4]arene, ZB4 is capable of accommodating a wide range of organic cations. However, ZB4 does not show

• binding behavior of ZB4 and lays the basis for the construction of stimuli-responsive materials with ZB4 as a major component. Keywords: conformations; host–guest chemistry; macrocycles; supramolecular chemistry; zorb[4]arene; Introduction Macrocyclic receptors are the principal workhorses used in

• network. We have carefully looked into the properties of oxatub[n]arenes and found that the macrocycles have many unique properties. For example, oxatub[4]arene has a wide guest scope and can bind almost all of the common organic cations [32]. It also shows conformational responses to solvent change [33

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• (trifluoroacetoxy)iodo]arene. Catalytic nitrene additions mediated by [bis(acyloxy)iodo]arenes. Tandem of C(sp3)–H amination/sila-Sonogashira–Hagihara coupling. Tandem reaction using a λ3-iodane as an oxidant, a substrate and a coupling partner. Synthesis of 1,2-diarylated acrylamidines with ArI(OAc)2

Hyper-reticulated calixarene polymers: a new example of entirely synthetic nanosponge materials

• Alberto Spinella,
• Marco Russo,
• Antonella Di Vincenzo,
• Delia Chillura Martino and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2018, 14, 1498–1507, doi:10.3762/bjoc.14.127

• preliminary tests to assess their supramolecular absorption abilities towards a set of suitable organic guests, selected as pollutant models. The synthesis was accomplished by means of a CuAAC reaction between a tetrakis(propargyloxy)calix[4]arene and an alkyl diazide. The formation of the polymeric network

• ]) between a heptakis(6-azido-6-deoxy)-β-cyclodextrin and a tetrakis(propargyloxy)calix[4]arene [11][31][32]. In this way, a random disposition of the co-monomer units linked by 1,2,3-triazole units is achieved. The obtained CyCaNSs benefit from several advantages. First, the properties of the material can

• ), in which the host monomers are joined by means of bis(1,2,3-triazole) subunits having different features. More in detail, four different nanosponges CaNS1-CaNS4 were obtained by reacting the 5,11,17,23-tetra-tert-butyl-25,26,27,28-tetrakis(propargyloxy)calix[4]arene (Ca-OP, Scheme 1a) with four

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• asymmetric phase-transfer catalysis based on inherently chiral calix[4]arenes, although the asymmetric induction observed remained moderate. Su et al. demonstrated a new approach for the design of a chiral binary integrative phase-transfer catalyst consisting of p-tert-butylcalix[4]arene and a cinchonine

• ammonium salt [38] (Scheme 2). Due to the failure of obtaining monobromo p-tert-butylcalix[4]arene derivative 6 directly from p-tert-butylcalix[4]arene using 1,2-dibromoethane in the presence of several bases, the synthetic route to calixarene-based chiral phase-transfer catalyst 7 comprises a four-step

• sequence including protection/deprotection steps for the benzyl groups. The catalytic efficiency of calix[4]arene-based phase-transfer catalyst 7 was evaluated in the benchmark reaction (Scheme 3) and compared with that of the chiral quaternary ammonium salt 8. The results obtained when 7 used as

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

• monoarylations, produces not only the aryl iodide, but also stoichiometric amounts of salt side-products, limiting the AE of these transformations to roughly 10–20% (Scheme 1, reaction (a)). In the second case, both organic residues (one carbon or heteroatom ligand plus the arene of the former aryl-λ3-iodane or

• describe an efficient α-arylation of a variety of 1,3-dicarbonyl derivatives 21 using [bis(trifluoroacetoxy)iodo]benzene (20a, PIFA). In this metal-free approach the target structures 22 are efficiently synthesised even without any initial prefunctionalisation of the arene moiety (Scheme 13). Remarkably

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

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• , reaction 1). Yet in the course of our study we also showed that the reactivity of the key bridged bromonium intermediate could also be steered towards non-cyclizing vicinal difunctionalizations using slightly different combinations of a (diacyloxyiodo)arene and a bromide salt. Indeed, (diacetoxy

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

• peptidocalix[4]arenes with arginine-rich short narrow groove binding residues on the lower rim of the calix[4]arene scaffold were reported by Soltani et al. in order to study the binding between well-matched and mismatched DNA duplexes [107]. Fluorescent titrations, ethidium bromide (EB) displacement assays

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• , transition metals feature prominently in such methods, but even recent examples employ stoichiometric metal mediators [4]. Metal-free methods by classic SNAr are also attractive, but only possible on very electron-deficient arene substrates [5]. Diaryliodonium salts are useful reagents for metal-free aryl

One-pot synthesis of diaryliodonium salts from arenes and aryl iodides with Oxone–sulfuric acid

• Natalia Soldatova,
• Pavel Postnikov,
• Olga Kukurina,
• Viktor V. Zhdankin,
• Akira Yoshimura,
• Thomas Wirth and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 849–855, doi:10.3762/bjoc.14.70

• –m in lower yields. Similar reactions of 3,5-bis(trifluoromethyl)iodobenzene (1d) with benzene and mesitylene formed the corresponding iodonium salts 3n and 3o in moderate yields. With electron-deficient arenes 2 such as chlorobenzene (2e) and benzene, an excess of sulfuric acid and arene was used to

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• by calix[4]arene derivatives 7 bearing the guanidine groups at the upper rim and O-(2-ethoxyethyl) groups at the lower rim [80]. The role of the latter groups was to improve solubility to hydroxylic solvents and to rigidify the calixarene system into the so-called cone conformation. HPNP (1) was used

• hydroxy function on phosphorus (Scheme 8). Similar results were obtained on using diphenylmethane as a scaffold 8 (Figure 8) [81]. A cyclohexylidene or adamantylidene substituent on the methylene carbon moderately enhanced the catalytic activity. Interestingly, the calix[4]arene-based agent 7 catalyzed

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• ) on the arene also deviated from the expected reaction course. These reactions failed to fully consume the starting materials 2u and 2v, even upon prolonged heating, which we discovered to be the result of 1b being also consumed through over-chlorination. 4-Methoxy derivative 2u gave trichloride 5u in

• as resulting from the stabilization of radical intermediates gained upon methoxy substitution [51], which permitted further chlorination of either the methyl or arene groups. To gain insight into the reaction mechanism we carried out two key control experiments. First, to test for rearrangement

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• , directing group-assisted arene C–H activation reactions have been extensively studied over the last few decades to offer a broad array of atom and step-economical methods for the synthesis of functionalized aromatic compounds [1][2][3][4][5][6]. Among various C–H transformations, the introduction of alkenyl

• (e.g., acrylates), and is challenging with unactivated and multisubstituted alkenes [11]. The hydroarylation of alkynes does not allow for the introduction of cycloalkenyl groups because of the unavailability of the corresponding alkynes. In light of such limitations, a coupling between arene

• ) from ketones [13][14][15][16][17]. Over the last several years, we and others have developed a series of directed arene C–H functionalization reactions with organic electrophiles under low-valent cobalt catalysis [18][19][20][21]. In particular, our group and the Ackermann group have independently

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• , indicating that the central cyclic peptide core probably has an expanded ring conformation. Garcia-Hartjes et al. synthesised and evaluated the GM1os linked calix[5]arene molecule 31 as shown in Figure 12, and found that compound 31 displayed 100,000 times more potency as compared to GM1os derivatives having

• inhibitor designed and synthesised by Pieters, and Bernardi et al. Cyclic inhibitors synthesised by Kumar et al. for CT. The star-shaped inhibitors reported by Fan, Hol and co-workers. Differently sized cyclic decavalent peptide core designed by Zhang et al. Calix[5]arene core-based pentavalent inhibitor

Synthesis of fluoro-functionalized diaryl-λ³-iodonium salts and their cytotoxicity against human lymphoma U937 cells

• Prajwalita Das,
• Etsuko Tokunaga,
• Hidehiko Akiyama,
• Hiroki Doi,
• Norimichi Saito and
• Norio Shibata

Beilstein J. Org. Chem. 2018, 14, 364–372, doi:10.3762/bjoc.14.24

• [65][66]. This synthesis was achieved by treating iodide 7 with the respective arene, m-CPBA, and trifluoromethanesulfonic acid at room temperature. The desired diaryliodonium salts 3p, 4b, 5a and 6a were obtained in good yields (72%, 86%, 81% and 92%, respectively) (Scheme 2). The newly synthesized

• for 1 h before the addition of 7 (1.0 equiv) and CH2Cl2 (6.0 mL/mmol ArI) in a round-bottomed flask. The solution was cooled to 0 °C followed by the dropwise addition of TfOH (1.7 equiv). The resulting mixture was stirred at room temperature for 2 h. It was then cooled to 0 °C and the arene (1.1 equiv

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• effect of the amine might be attributed to the resonance structures of imidazole (Table 1, entry 11) [72]. To determine the influence of substituents on the phenyl group, various arene(methyl)sulfanes 7l–p were tested (Table 1, entries 12–16,). Simple phenyl and electron-donating compounds 7l and 7m did

• -pot sequential synthesis of the trisubstituted 5-(pyridine-2-yl)thiophenes 8a. Substrate: amalonitrile; b5,5-dimethylcyclohexane-1,3-dione. The substitution reaction with MeOH. Examination of N,S-acetals substituted with a heterocycle (7aa–k) or an arene (7l–p). 1H NMR studies of Meldrum’s acid-based

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

• corresponding hydroxylated arene) was readily removable by extraction or column chromatography. Later, the group of Beller [42] described another example of copper-catalyzed trifluoromethylation reactions of aryl- and vinylboronic acids with CF3SO2Na as the trifluoromethyl source (Scheme 23). The

• groups were tolerated in these conditions, such as sulfonate, nitro, ester, amide, ether, and even unprotected hydroxy groups. In addition, arene rings bearing chloro and iodo groups did not interfere with the transformation, which promised further conversion at the halogenated positions. It was notable