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

Structure–efficiency relationships of cyclodextrin scavengers in the hydrolytic degradation of organophosphorus compounds

• Sophie Letort,
• Michaël Bosco,
• Benedetta Cornelio,
• Frédérique Brégier,
• Sébastien Daulon,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2017, 13, 417–427, doi:10.3762/bjoc.13.45

• of the agents. The degradation efficiency was found to be dependent on the relative position of the heterocycle towards the reactive group as well as on the nature of the organophosphorus derivative. Keywords: cyclodextrin; decontamination; enzyme mimic; nerve agents; organophosphorus pesticides

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study

• Michael L. McKee,
• Grzegorz Mlostoń,
• Katarzyna Urbaniak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2017, 13, 410–416, doi:10.3762/bjoc.13.44

• Supporting Information File 1, Table SI1) in the broken symmetry solution. The further conversion of the conformers of the intermediate diradical 12 into the macroheterocycle 9, the six-membered 1,4-dithiane 13, and the ten-membered heterocycle 14, respectively, is governed by two factors: the unpaired spin

• dimer 12, followed by the C–C bond formation involving the C(2) centers of the selenophene rings to yield the obtained twelve-membered heterocycle 9. In extension of the study, calculations were performed on the related symmetrical thiobenzophenone S-methanide by the same computational approach (see

Continuous N-alkylation reactions of amino alcohols using γ-Al₂O₃ and supercritical CO₂: unexpected formation of cyclic ureas and urethanes by reaction with CO₂

• Emilia S. Streng,
• Darren S. Lee,
• Michael W. George and
• Martyn Poliakoff

Beilstein J. Org. Chem. 2017, 13, 329–337, doi:10.3762/bjoc.13.36

• could be synthesised by incorporation of CO2 from the supercritical solvent into the product. Keywords: continuous flow; heterocycle; N-alkylation; self-optimisation; supercritical CO2; Introduction N-alkylated amines are an important motif present in a range of pharmaceutically and industrially

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• determined using computational calculations. The values found for the HOMO coefficient and charge density were 0.009 and −0.259, respectively, which are small enough to promote the nucleophilic attack that leads to a heterocycle. The structures of all the compounds were confirmed by 1H and 13C NMR, LC–MS

3D printed fluidics with embedded analytic functionality for automated reaction optimisation

• Andrew J. Capel,
• Andrew Wright,
• Matthew J. Harding,
• George W. Weaver,
• Yuqi Li,
• Russell A. Harris,
• Steve Edmondson,
• Ruth D. Goodridge and
• Steven D. R. Christie

Beilstein J. Org. Chem. 2017, 13, 111–119, doi:10.3762/bjoc.13.14

• equipment, allowing automated online and inline optimisation of the reaction medium. This set-up allowed the optimisation of two reactions, a ketone functional group interconversion and a fused polycyclic heterocycle formation, via spectroscopic and chromatographic analysis. Keywords: 3D printing; inline

• allow a much larger chemical space to be analysed (<200 °C). The formation of a fused polycyclic heterocycle 5 (Scheme 2), from pentafluoropyridine (3) and 2-(methylamino)phenol (4), was chosen as this would generate a more complex optimisation set with two starting materials, the reaction product as

• the SIMPLEX optimisation of the fused polycyclic heterocycle 5. Two optimal data points at 0.24 mL/min and 156 °C, and 0.24 mL/min and 170 °C were found. SLM reactor design RD3 (left), CAD model of RD3 (right). External dimensions of RD3 are 89 (length) × 27 (width) × 38 mm (depth). Optimisation plot

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• electronegativity of the R group is probably also important; when more electropositive (as Si), the oxygen atoms become more electron rich and their repulsion becomes larger. Changing the conformation of a heterocycle has, as mentioned, been studied using the piperidine model system. The pKa of the corresponding

From betaines to anionic N-heterocyclic carbenes. Borane, gold, rhodium, and nickel complexes starting from an imidazoliumphenolate and its carbene tautomer

• Ming Liu,
• Jan C. Namyslo,
• Martin Nieger,
• Mika Polamo and
• Andreas Schmidt

Beilstein J. Org. Chem. 2016, 12, 2673–2681, doi:10.3762/bjoc.12.264

• ], versatile organocatalysts [8][9][10], and starting materials for heterocycle syntheses [11][12][13]. Consequently books [14][15][16] and reviews cover the range from NHC structures in the light of their early history [17], syntheses [6][18], coordination chemistry [19][20], and catalysis [21][22], to

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

• Vladimir A. Stepchenko,
• Anatoly I. Miroshnikov,
• Frank Seela and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2016, 12, 2588–2601, doi:10.3762/bjoc.12.254

• the bases is a substrate for both enzymes, UP and TP, and the glycosylation efficiency depends, as might be expected, on the C-5 substituent of the heterocycle, viz., glycosylation of 6-azauracil occurs more efficiently under UP catalysis, whereas the 6-azathymine synthesis proceeds more efficiently