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

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

• -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

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

• reaction with different electron-rich, halogenated or heterocycle substituted alkynes, affording the respective products in good to moderate yields. Strongly electron-withdrawing nitro, acyl or cyano groups were not suitable. In accordance to the proposed mechanism, the reaction with 2-iodothioanisoles

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• azlactone dimer, which is a versatile heterocycle containing two stereogenic centers (Figure 1). Kobayashi and co-workers demonstrated the rich reactivity of azlactones conducting the dimerization reaction using strong bases as catalysts; however, higher temperatures and long reaction times were required

Regioselective decarboxylative addition of malonic acid and its mono(thio)esters to 4-trifluoromethylpyrimidin-2(1H)-ones

• Sergii V. Melnykov,
• Andrii S. Pataman,
• Yurii V. Dmytriv,
• Svitlana V. Shishkina,
• Mykhailo V. Vovk and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2017, 13, 2617–2625, doi:10.3762/bjoc.13.259

• (Table 2, entries 1–16). The presence of the ester functionality at position 5 of the heterocycle led to product mixtures if toluene was used as solvent so that products 4j–m could not be obtained selectively and separated. In DMSO solution, the corresponding Michael-type adducts 5j–m were smoothly

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• cannot exclude an alternative route when the carbenoid interacts with the cyano group to yield an oxazole heterocycle [39][40][41][42][43][44][45]. Herein we present the first detailed results of this study. Results and Discussion To determine the scope and limitations of these reactions, several

• photosensitivity and hence could be used in OLED devices [68]. Also these compounds display high nucleophilicity in reactions with electrophiles which are often accompanied by a variety of thiophene heterocycle transformations, and hence could be successfully used for their further functionalization [69

A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway

• Dmitry Yu. Vandyshev,
• Khidmet S. Shikhaliev,
• Andrey Yu. Potapov,
• Michael Yu. Krysin,
• Fedor I. Zubkov and
• Lyudmila V. Sapronova

Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252

• [1,5-b]pyridazines along route B, 1-aminoimidazoles with no substituents at the C-5 atom of the original heterocycle and 1,3-dielectrophilic reagents are used, e.g., 1,3-diketones [24][25][26], β-ketoesters [24], α,β-unsaturated ketones [27][28], including those obtained in situ [29][30] or containing

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

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• ] (Figure 1B). For this reason, the adamantylation of compounds 5 and 6 led to mixtures of N3- and N4-adamantylated isomers, which reisomerized into each other likely via the formation of an adamantyl cation and starting NH-heterocycle. The unambiguous determination of N-adamantylation site(s) in

• ]triazinone 19-15N2. Previously, the same approach was described for the incorporation of 15N atoms in azole and azine rings of compound 4 [38]. Heterocycle 20-15N2 was obtained by the treatment of 19-15N2 with hydrobromic acid according to a procedure described for 6-nitro-1,2,4-triazolo[5,1-c][1,2,4]triazin

• observed by NMR spectroscopy in DMSO solution (≈10:7). Interestingly, for 15a, the major conformer corresponds to a rotameric state with a screened N1 atom, but in the major conformer of 15b, the N2 atom of the heterocycle is screened. Notably, similar structural disorder was previously observed in the

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• time, the 1,2,3-triazoles became the heterocycle of choice in drug discovery, due to their favourable pharmacokinetic and safety profiles, hydrogen-bonding capability, moderate dipole moment, rigidity and stability under in vivo conditions [5][6]. Also, the ability of 1,2,3-triazoles to act as amide

• derivatives and it was largely helpful for calculating the Raman spectra for monitoring purposes. It corroborated the substitution of the phenyl-1-(1,2,3-triazolyl)methyl unit at O-4 position of the quinolone heterocycle and formation of the 1,2,3-triazole ring in compounds 5–8 (Figure 5 and Supporting

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

• afforded azafulvene derivatives 91 (Scheme 34) [82]. Remarkably, the formation of five-membered cyclic nitrone through N-attack of the oxime on the cyano group is more preferable over the six-membered N–O heterocycle. C-Nucleophiles possessing leaving groups have been also used in the construction of N–O

High-speed vibration-milling-promoted synthesis of symmetrical frameworks containing two or three pyrrole units

• Marco Leonardi,
• Mercedes Villacampa and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2017, 13, 1957–1962, doi:10.3762/bjoc.13.190

• vibration milling (HSVM) [14][15]. The importance of pyrrole frameworks stems from the status of this heterocycle as a privileged structure in drug discovery due to its presence as a structural core in molecules that are able to bind various receptors [16]. Results and Discussion Our route to the target

One-pot multistep mechanochemical synthesis of fluorinated pyrazolones

• Joseph L. Howard,
• William Nicholson,
• Yerbol Sagatov and
• Duncan L. Browne

Beilstein J. Org. Chem. 2017, 13, 1950–1956, doi:10.3762/bjoc.13.189

• has culminated in the development of a two-step, one-jar protocol for heterocycle formation and subsequent fluorination that has been successfully applied across a range of substrates, resulting in 12 difluorinated pyrazolones in moderate to excellent yields. Keywords: fluorination; heterocycles

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

• also observed that an oven-dried catalyst worked effectively to give 99% of product with 99% ee up to few cycles. Heterocycle synthesis Multicomponent reactions [135], cyclo-condensations and cascaded transformations are common strategies to make heterocyclic ring [113] systems like pyrroles, pyrans

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• -oxazolines, which are valuable heterocycles found in ligand scaffolds, natural products such as the leupyrrins [18][19], and potential pharmaceuticals (Figure 1) [20][21][22]. Traditional routes to this heterocycle include the dehydration of amino alcohols with carboxylic acids, however, this process

An effective Pd nanocatalyst in aqueous media: stilbene synthesis by Mizoroki–Heck coupling reaction under microwave irradiation

• Carolina S. García,
• Paula M. Uberman and
• Sandra E. Martín

Beilstein J. Org. Chem. 2017, 13, 1717–1727, doi:10.3762/bjoc.13.166

• containing a nitrogen heterocycle (entries 1–3, Table 2) react better than aryl bromides with electron-donating groups (entries 4–7, Table 2). In the latter cases, higher temperatures, or a slight increase in reaction time and catalyst loading were needed to obtain the desired (E)-stilbenes 6–9 in good

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• -methoxyphenoxy)alkyl]carbazole fragment. Such readily functionalizable heterocycle as carbazole was used as a main starting compound for their preparation. The investigation of the optical properties has shown that the positive solvatochromism is inherent to the chromophores containing an electron-withdrawing

• advantages when compared with other conjugated aromatic systems [2][3][4]. First of all, 9H-carbazole is a relatively cheap starting material. At the same time, its fully aromatic system renders this heterocycle a good chemical and environmental stability. Nucleophilic substitution of a 9H atom proceeds

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• of the reagents. Moreover, the changes in the reaction conditions may lead to the change of the mechanism of the arylation process. For example, the arylation of benzoxazole mediated by Pd(OAc)2/PPh3 presumably includes the cleavage of the 5-membered heterocycle with the formation of the transient

Synthesis of the heterocyclic core of the D-series GE2270

• Christophe Berini,
• Thibaut Martin,
• Pierrik Lassalas,
• Francis Marsais,
• Christine Baudequin and
• Christophe Hoarau

Beilstein J. Org. Chem. 2017, 13, 1407–1412, doi:10.3762/bjoc.13.137

• organized into 32 families and 5 series [1][2][3][4][5][6][7][8][9]. The particularity of these molecules is the interruption of the modified cyclopeptide chain by a more complex nitrogen-containing heterocycle found at different oxidation states (from series a to e) and bearing many azole units. They

• with a sophisticated tris-1,3-diazole, judiciously prepared through direct C–H arylation method, to synthesize the trithiazolylpyridine intermediate (Figure 1). The latter was then transformed to heterocycle core of GE2270 by adding a final bromination/Hantzsch sequence to build the last 2,4