An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• were unable to access 2 (Scheme 7). Instead, the major product isolated in both cases was novel heterocycle 35. It is likely that cleavage of one of the pivaloxymethyl groups, followed by intramolecular cyclisation, results in the formation of 35. Microwave heating of 33 in the presence of DBU also

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

•  2), while the Cu(II)-mediated ditosylation in water/acetonitrile (ACN) mixture gave only two positional ditosyl-β-CD isomers in a ratio 6A,6C:6A,6D = 58:42, (reaction 2, Scheme 2). Tosylation in pyridine is known to be catalyzed by the oriented inclusion of the aromatic heterocycle into the cavity

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• systems possessing a pyrazole ring fused to an oxygen-containing six-membered heterocycle are present in a wide variety of biologically active compounds. For example, the 1,4- and 2,4-dihydropyrano[2,3-c]pyrazole ring systems [1] often represent the main structural motifs of anticancer [2][3][4], anti

Tandem copper and photoredox catalysis in photocatalytic alkene difunctionalization reactions

• Nicholas L. Reed,
• Madeline I. Herman,
• Vladimir P. Miltchev and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2019, 15, 351–356, doi:10.3762/bjoc.15.30

• -donating and electron-withdrawing substituents smoothly undergo oxyamination (9–12), as do ortho-substituted styrenes (13). The presence of an electron-rich heterocycle is also tolerated (14), without any evidence of oxidative decomposition of this sensitive functional group. Modifications to the alkyl

Mn-mediated sequential three-component domino Knoevenagel/cyclization/Michael addition/oxidative cyclization reaction towards annulated imidazo[1,2-a]pyridines

• Olga A. Storozhenko,
• Alexey A. Festa,
• Delphine R. Bella Ndoutoume,
• Alexander V. Aksenov,
• Alexey V. Varlamov and
• Leonid G. Voskressensky

Beilstein J. Org. Chem. 2018, 14, 3078–3087, doi:10.3762/bjoc.14.287

• the redox potentials of three or more reactants at a time and employment of a sequential one-pot strategy may become one of the reasonable solutions. The vast biological activity of the compounds, bearing the imidazo[1,2-a]pyridine scaffold makes this heterocycle of great importance to the fields of

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• which a heterocycle is annellated to the benzene ring of the coumarin skeleton. In particular the latter group is often further divided into sections according to ring size (five-membered rings: furanocoumarins; six-membered rings: pyranocoumarins) and location of the annellated ring (linear vs angular

• sequence for the construction of the 8-allylcoumarin scaffold and combinations of double bond isomerization and ring-closing olefin metathesis for the annellation of a second heterocycle. Pyran-2-one-annellated coumarins, which are scarcely available in synthetically useful yields through classical methods

Generation of 1,2-oxathiolium ions from (arysulfonyl)- and (arylsulfinyl)allenes in Brønsted acids. NMR and DFT study of these cations and their reactions

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov,
• Olesya V. Khoroshilova and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2018, 14, 2897–2906, doi:10.3762/bjoc.14.268

• positive charge (see data in Table 1 and Table 2). An alternative mechanism of the formation of alcohol 4a includes the attack of H2O on the sulfur electrophilic center giving intermediate D, which is rearranged into alcohol Z-4a. Preparation of sulfur heterocycle 5a at high reaction temperature (Table 3

Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence

• Gergő Mótyán,
• László Mérai,
• Márton Attila Kiss,
• Zsuzsanna Schelz,
• Izabella Sinka,
• István Zupkó and
• Éva Frank

Beilstein J. Org. Chem. 2018, 14, 2589–2596, doi:10.3762/bjoc.14.236

• -bulky heterocycle containing O, N or S atoms attached to position C-17 of the sterane skeleton with the lone electron pairs capable of coordinating with the heme iron at the active site; (ii) a N atom at either position 3′ or 4′ relative to the atom through which the heterocyclic ring is connected to

• the sterane framework; (iii) a hydroxy or keto group at C-3 and (iv) the presence of a C16–C17 double bond, which facilitates the inhibitory effect but is not an essential requirement. Some 17-heterocycle-substituted androstanes, even those that lack the structural features described above, are also

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• acid residue required for the synthesis of key arylquinolines involved in an HIV integrase project. Keywords: cyclodehydration; HIV integrase; isatoic anhydride; masked acyl cyanide; quinoline; Introduction In stark contrast to the prevalence of the quinoline heterocycle in natural products [1

• heterocycle at position 4 is installed by Suzuki coupling with iodide 3a that is synthesized in three steps from ethyl aryl oxalate 4a. The α-ketoester side chain at position 3 was installed by selective halogen-metal exchange of iodide 5a with isopropylmagnesium chloride lithium chloride complex followed by

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• numerous organic compounds [24][25][26][27][28]. The amazingly rapid and broad permeation of 1,2,3-triazoles to multidisciplinary areas can majorly be attributed to the occurrence of robust synthetic methods toward this heterocycle. The copper-catalyzed click [3 + 2] cycloaddition of azides and alkynes [29

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

• Edwin Alfonzo,
• Jesse W. L. Mendoza and
• Aaron B. Beeler

Beilstein J. Org. Chem. 2018, 14, 2308–2312, doi:10.3762/bjoc.14.205

• alcohols and aldehydes. Keywords: Corey–Chaykovsky; epoxide; heterocycle; one-pot; ylide; Introduction Epoxides have historically served as strategic functional groups in target-oriented synthesis [1][2][3][4]. Common examples of their utility include stereospecific ring opening [5][6][7], rearrangements

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

• heterocycle, and the benzene moiety can tolerate all manner of substituents in all positions, however, only mono-substituted systems are explored. This is a powerful procedure, which allows for the circumvention of traditional Pd or Cu catalysed couplings of heteroarenes, which are notoriously difficult. A

• encompass structurally diverse and relatively delicate scaffolds, making it suitable for LSF, would make this an incredibly valuable tool to the medicinal chemist. 3 Heterocycle formation The importance and prevalence of heterocyclic systems in medicinal chemistry cannot be overstated. Although reactions

• the anti-configuration in all cases. In addition, the option for oxidation to the oxazole or thiazole is always enticing as a way of easily accessing a diverse set of molecules. Immediately akin to the oxazole moiety is the oxadiazole heterocycle, which exhibits similar properties. There are several

Preparation and X-ray structure of 2-iodoxybenzenesulfonic acid (IBS) – a powerful hypervalent iodine(V) oxidant

• Irina A. Mironova,
• Pavel S. Postnikov,
• Rosa Y. Yusubova,
• Akira Yoshimura,
• Thomas Wirth,
• Viktor V. Zhdankin,
• Victor N. Nemykin and
• Mekhman S. Yusubov

Beilstein J. Org. Chem. 2018, 14, 1854–1858, doi:10.3762/bjoc.14.159

• ) heterocycle (2-iodosylbenzenesulfonic acid), while the oxidation of sodium 2-iodobenzenesulfonate in neutral aqueous solution gives the iodine(V) products. Keywords: hypervalent iodine; iodine; 2-iodoxybenzenesulfonic acid; oxidation; X-ray; Introduction Recently, the interest in synthetic applications of

• ) heterocycle, 2-iodosylbenzenesulfonic acid (4) as main product. The direct oxidation of 2-iodobenzenesulfonic acid (2) with Oxone leads to the formation of the desired IBS (1, Scheme 1), however, contaminated with inorganic impurities. Because of the high solubility of IBS in water, this mixture is difficult

• of IBS, 2-iodosylbenzenesulfonic acid, by using periodic acid as an oxidant. We have demonstrated that the oxidation of free 2-iodobenzenesulfonic acid under acidic conditions affords an iodine(III) heterocycle, while the oxidation of sodium 2-iodobenzenesulfonate in neutral aqueous solution gives

Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• achieved when a third heterocycle, especially a 1,2,4-triazolo moiety, was attached to the seven-membered ring as part of 1,4-benzodiazepine [13][14]. Among various reported 1,2,4-triazole-annulated 1,4-benzodiazepines, triazolam (I), estazolam (II), alprazolam (III) and pyrazolam (IV) are prominent

Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally generated acyl(quinoxalin-2-yl)ketenes by Schiff bases

• Svetlana O. Kasatkina,
• Ekaterina E. Stepanova,
• Maksim V. Dmitriev,
• Ivan G. Mokrushin and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2018, 14, 1734–1742, doi:10.3762/bjoc.14.147

• (quinoxaline fused by a six-membered heterocycle at the [a]-side) are promising biologically active compounds. Recent research studies revealed that they can act as inhibitors of poly(ADP-ribose) polymerase (PARP) [3], inhibitors of hepatitis C virus [4], 5-HT2C agonists [5][6][7], substances for controlling

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• branch-cells, (ii) basicity and conformational nature of the diaza-six-membered saturated heterocycle as linker and (iii) the global molecular shape, the resulted 4-aminophenol-based melamines displayed relevant redox properties [36] and, in some cases, selective aptitudes to produce MOFs (metal-organic

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

• been further extended to the synthesis of a new series of molecules 77, where the central thiophene moiety is replaced by a 6-membered heterocycle, which is substituted by a gem-dimethyl or a cyclopropyl group. In this case, the reaction can be performed under metal-free conditions in the presence of a

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

• triazole ring can be confirmed by the examination of the fingerprint region. According to literature, the presence of the heterocycle linker is accounted for by the occurrence of a tiny signal at 1242 cm−1 [11]; moreover, new bands are present in the spectrum of CaNS2 at 1296, 1050 and 1026 cm−1, which

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

• reaction sequence proceeds under metal-free conditions, the selective transfer of the more electron-deficient aryl group of the unsymmetrical iodonium salts 1 is achieved. The N-arylated heterocycle NAr1 then serves as the directing group in the following ortho-C–H functionalisation with the iodoarene as

Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation

• Mark Kelada,
• John M. D. Walsh,
• Robert W. Devine,
• Patrick McArdle and
• John C. Stephens

Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104

• groups. Keywords: microwave-assisted synthesis; nitrogen-fused heterocycle; one-pot; pyrimidinone; Introduction The pyrazolo[1,5-a]pyrimidinone is a fused nitrogen-containing heterocyclic system and is of interest due to its role as a basic core scaffold in many bioactive and pharmaceutically relevant

Preparation, structure, and reactivity of bicyclic benziodazole: a new hypervalent iodine heterocycle

• Akira Yoshimura,
• Michael T. Shea,
• Cody L. Makitalo,
• Melissa E. Jarvi,
• Gregory T. Rohde,
• Akio Saito,
• Mekhman S. Yusubov and
• Viktor V. Zhdankin

Beilstein J. Org. Chem. 2018, 14, 1016–1020, doi:10.3762/bjoc.14.87

• , Duluth, MN 55811, USA, Division of Applied Chemistry, Institute of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo 184-8588, Japan 10.3762/bjoc.14.87 Abstract A new bicyclic organohypervalent iodine heterocycle derivative of benziodazole was prepared by

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• -dideazaadenine C-nucleosides [63][64][65][69][70]. A. Reaction of D-ribonolactone and lithiated heterocycle leading to C1'-substituted C-nucleosides. Steroechemical scrambling is observed when ring opened form of ribose is employed during nucleophilic substitution. B. Synthesis of C2' C-nucleosides using

Sequential Ugi reaction/base-induced ring closing/IAAC protocol toward triazolobenzodiazepine-fused diketopiperazines and hydantoins

• Robby Vroemans,
• Fante Bamba,
• Jonas Winters,
• Joice Thomas,
• Jeroen Jacobs,
• Luc Van Meervelt,
• Jubi John and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 626–633, doi:10.3762/bjoc.14.49

• heterocycle formation and the other an IAAC. Unlike some of the reported strategies using Cu-catalyzed IAAC [13][15], we postulated that the intramolecular dipolar cycloaddition would proceed under thermal conditions (metal-free) due to the close proximity of the azide and similar functionalities in the

• conformational restrictions prevent the side chains on the benzodiazepine bearing the amide and halogen to be in close proximity, which is needed for the reaction to proceed. The generality of the developed fused-heterocycle synthesis was studied with substituted azidoaldehyde, isocyanides and chloroacetic acid

• successful in synthesizing chloro derivatives 7i and 7j from 2-azido-4-chlorobenzaldehyde (1c). The multiring-fused heterocycle synthesis was also tried with an azidobenzaldehyde bearing electron-donating substituents; the reaction with 2-azido-4,5-dimethoxybenzaldehyde (1d) yielded the product 7k in lesser

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• benzyl or heterocycle groups and release of the unmodified sequences. Modifications at the internucleotide linkage: ONs containing either 5-nitro-2-furylmethyl or 5-nitro-2-thiophenylmethyl modifications at some internucleoside phosphates were converted to native (dT)n with good hypoxia selectivity in

Recent advances on organic blue thermally activated delayed fluorescence (TADF) emitters for organic light-emitting diodes (OLEDs)

• Thanh-Tuân Bui,
• Fabrice Goubard,
• Malika Ibrahim-Ouali,
• Didier Gigmes and
• Frédéric Dumur

Beilstein J. Org. Chem. 2018, 14, 282–308, doi:10.3762/bjoc.14.18

• with the azasiline donor, OLEDs displaying the unprecedented EQE of 22.3% were obtained [46]. As specificity, azasiline is a 6-membered heterocycle comprising a silicon atom introduced instead of a carbon atom to enlarge the HOMO–LUMO gap and lower the HOMO level. Due to the sp3 hybridization of the