An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• couplings [13][14], and photooxygenation reactions [15][16]. Similarly, Zheng has reported oxidatively initiated indole synthesis [17] and [3 + 2] cycloaddition [18][19] reactions using photocatalyst 2. Finally, a variety of transition metal complexes bearing bipyrazyl ligands have been prepared and

Palladium-catalyzed 2,5-diheteroarylation of 2,5-dibromothiophene derivatives

• Fatma Belkessam,
• Aidene Mohand,
• Jean-François Soulé,
• Abdelhamid Elias and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 2912–2919, doi:10.3762/bjoc.10.309

• knowledge, so far sequential Pd-catalyzed direct couplings using 2,5-dihalothiophene derivatives have not been described. Therefore, the discovery of effective general conditions, for the direct coupling of heteroarenes at both C2 and C5 positions of 2,5-dihalothiophene derivatives, would constitute a

Aspergiloid I, an unprecedented spirolactone norditerpenoid from the plant-derived endophytic fungus Aspergillus sp. YXf3

• Zhi Kai Guo,
• Rong Wang,
• Wei Huang,
• Xiao Nian Li,
• Rong Jiang,
• Ren Xiang Tan and
• Hui Ming Ge

Beilstein J. Org. Chem. 2014, 10, 2677–2682, doi:10.3762/bjoc.10.282

• spectra of 1 allowed all protons to be assigned to their respective carbons. The 1H,1H three-bond couplings from H-1 to H-3 observed in the COSY experiment established a spin system from C-1 to C-3 (Figure 2). The COSY correlation between H-8 and H-9 revealed C-8 to C-9 connectivity. A terminal vinyl

• moiety H-14/H2-15 was also confirmed by 1H,1H-COSY correlations. The hydroxy group (δH 5.21) attached to C-5 and the other hydroxy group (δH 5.04) attached to C-11 were identified by the 1H,1H couplings (acquired in DMSO-d6) with H-5 (δH 2.81), and H-11 (δH 3.76), respectively. HMBC correlations from two

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• small 3J2-H,3-H couplings. Whereas in the computed solution conformers of trans-7a,b (Figure 2), the oxazepine ring adopts a boat conformation showing a trans-diaxial relationship with the adjacent 3-Hax. In accordance with the calculations, the measured values of the 3J2-Hax,3-H (11.5 and 3.2 Hz

• ) corroborate that the couplings between 2-Hax and 3-Hs derive from trans-diaxial (ω2-Hax,C-2,C-3,3-Hax ≈ 180°) and gauche (ω2-Hax,C-2,C-3,3-Heq ≈ 60°) orientations, which is only feasible with the trans relative configuration of 7a,b. Thus in the course of the cyclization, the attack of the carbanion to the

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• convenient methods to prepare nitrogen-containing tetracyclic compounds incorporating the bioactive indole motif in organic chemistry and medicinal chemistry. Over the past decades, copper catalysts have been proven highly powerful for various cross-coupling reactions, including Ullmann-type couplings of

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• '-UUGCA-5', has been prepared on a precipitative tetrapodal tetrakis(4-azidomethylphenyl)pentaerythritol support. The 3'-terminal nucleoside was coupled to the support as a 3'-O-(4-pentynoyl) derivative by Cu(I) promoted 1,3-dipolar cycloaddition. Couplings were carried out with 1.5 equiv of the building

• second after the 5'-deprotection. Owing to the symmetrical tetrapodal structure of the support, the completeness of couplings may be verified by 1H NMR spectroscopy. We now report on the synthesis of short oligoribonucleotides on this support. Unfortunately, commercially available building blocks that

• synthetic cycle was composed of three steps, as usual: coupling, oxidation and deprotection. Couplings were carried out in a 1:1 mixture of MeCN and DMF under N2 using 1.5 equiv of the respective phosphoramidite building block per a support-bound 5'-hydroxy group. After coupling, the phosphite triester

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• -membered ring. Conformational analysis using vicinal proton–proton scalar couplings (3JHH) of ring protons obtained from 1H NMR spectra is a traditional and well-established experimental method. 3JHH encodes information on the exocyclic dihedral angle between coupled protons based on the Karplus

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• of aryl- and halogen-substituted 1,3-oxazines, taking into account that the latter are potential candidates for metal-catalyzed couplings and thus allow further modifications. Results and Discussion The theoretical study of the reaction mechanism was started with an evaluation of the thermodynamic

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• that this nitrogen atom lacks of sufficient couplings to protons, thus disabling the necessary coherence transfer (19F,15N HMBC spectra were not possible with the equipment at hand). For N-1, with pyrazole derivatives 4 and 6 remarkably larger 15N chemical shifts were detected (−158.8 to −160.2 ppm

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• . Unnatural divalent rigid p-terphenyl-linked C-aryl glycosides with 2.0 nm dimension are available using Suzuki cross-couplings. The key compound, a p-bromophenyl-substituted 1,2-oxazine, was prepared by a stereoselective [3 + 3]-cyclization of a D-isoascorbic acid-derived (Z)-nitrone and lithiated TMSE

• -couplings to form biphenyl aminopyran or p-terphenyl-linked dimers. Hydrogenolysis afforded new unnatural aminosugar mimetics. Zinc in the presence of acid or samarium diiodide were examined for the N–O bond cleavage in order to obtain the rigid p-terphenyl-linked C-glycosyl dimers. Keywords: carbohydrate

• are among the best methods to prepare C-arylglycosides, C-nucleosides and C-glycosidic oligomers when new artificial pharmacophores are approached [17]. With Suzuki cross-couplings C-glycoside analogues of phloriain with antidiabetic properties [18] or aryl-scaffolded dimers and trimers were

The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: the electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases

• Ilja V. Fateev,
• Konstantin V. Antonov,
• Irina D. Konstantinova,
• Tatyana I. Muravyova,
• Frank Seela,
• Roman S. Esipov,
• Anatoly I. Miroshnikov and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2014, 10, 1657–1669, doi:10.3762/bjoc.10.173

• the less stable conformer (ET = −732297.1 kcal/mol) with a twist 3T2 spatial structure of the pentofuranose ring is in accordance with the experimental coupling constant of 5.40 Hz, whereas those of H-1/H-2 and H-2/H-3 disagree with the relevant couplings (Figure 3; for detailed information, see Table

• S3 in Supporting Information File 1). Taken together, these data suggest the population of two–three conformers and the experimental couplings are the average values of the corresponding vicinal atoms. It is noteworthy that the vicinal coupling constants H-1/F (9.95 Hz), H-3/F (24.39 Hz) and H-1/P

• (6.5 Hz) taken from the 19F and 31P NMR spectra, respectively, are in fair agreement with the calculated structures and the analogous couplings obtained from the 1H NMR spectrum. A similar analysis of the stereochemistry of the α-D-arabinofuranose-1-phosphate (Ara-1P) revealed a very close resemblance

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• yield after HPLC purification and gave the expected multicharged ions by electrospray mass spectrometry (Table 1). Conclusion In summary, we have developed the first synthesis of hGCs using a one-pot orthogonal chemoselective route by using dual thiol–chloroacetyl and thiol–ene couplings. The

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• = pulse length for bipolar pulses. All diffusion spectra were processed in Mat NMR [47]. Glycodendrimer synthesis Procedure A: multiple CuAAc couplings on polypropargylated cores To a solution of polypropargylated core (1.00 equiv) and complementary azido synthon (1.25 equiv/propargyl) in a THF/H2O

Hindered aryl bromides for regioselective palladium-catalysed direct arylation at less favourable C5-carbon of 3-substituted thiophenes

• Rongwei Jin,
• Charles Beromeo Bheeter and
• Henri Doucet

Beilstein J. Org. Chem. 2014, 10, 1239–1245, doi:10.3762/bjoc.10.123

• thiophenes without the use of a blocking group at carbon C2. To our knowledge, ortho-substituents on aryl bromides have not been employed as directing groups for palladium-catalysed direct arylation of 3-substituted thiophenes. The use of congested aryl bromides for such couplings would certainly modify the

• , allow the preparation of 2,5-diarylthiophenes with two different aryl units in two steps. The major byproduct of these couplings is KBr/AcOH instead of metallic salts as with more classical coupling procedures. For these reasons, this process gives an economically viable access to C5-arylated 3

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• [20], the reaction yields of the monomer attachment to the growing chain have dropped to 50% after the two first couplings although the addition of the first and the second monomer units provided a good yield (95%). The change of the solvents in SPPS of MorGly oligomers (see Table 1) similarly to the

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• available by copper-catalyzed aryl couplings or Buchwald–Hartwig reactions [22]. Pyrazol-3-ylidenes rearrange similarly to quinolines [17]. We report here on two unexpected rearrangements of indazol-3-ylidene, and trapping reactions of the N-heterocyclic carbene with rhodium. Results and Discussion On

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• couplings [16][23], the classical formation of ester [12][17], amide [25][26] or imide [27] bonds between CDs or amino CDs and acid- or anhydride-linkers, and finally urea/thiourea bonds [28][29]. However, the obvious advantages of the Staudinger ligation (high reaction rates, absence of a catalyst, aqueous

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• spectra of 14 and 20 display characteristic signals around 11–15 ppm with 2JFP couplings for CF3 bearing substrates. The CHF2 bearing also possessed 2JFP couplings of 75–95 Hz. The 19F NMR spectra were characterized by signals in the region −75 ppm for CF3 derivatives and −137 ppm for CHF2 ones. Some

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• combination of deprotection and activation is also possible and is found in the literature as an Ugi Deprotection/Activation–Cyclisation (UDAC). In addition, other MCR-post-condensation reactions, especially for macrocycles, include intramolecular aryl couplings, amidations, SnAr reactions, nucleophilic

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• them on a mesoporous support, i.e., MCM-41. The authors tested them in A3-couplings and found that, although under homogeneous conditions the conversion to the respective propargylamine was higher than under heterogeneous ones, the heterogenized complexes were stable, recyclable for at least six cycles

The Flögel-three-component reaction with dicarboxylic acids – an approach to bis(β-alkoxy-β-ketoenamides) for the synthesis of complex pyridine and pyrimidine derivatives

• Mrinal K. Bera,
• Moisés Domínguez,
• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 394–404, doi:10.3762/bjoc.10.37

• obtained heterocycles by palladium-catalyzed couplings or by oxidations are reported. We also describe the simple synthesis of a structurally interesting macrocyclic bispyrimidine derivative incorporating a 17-membered ring, whose configuration was elucidated by DFT calculations and by subsequent reactions

• between the two isomers. According to TLC and NMR spectroscopy, macrocycle 34 was isolated as a single compound. Due to the symmetry of 34 no couplings of the olefinic protons in its 1H NMR spectrum can be observed. Thus at this stage, we were unable to assign the configuration of the double bond. In lack

• addition we exemplarily investigated subsequent transformations of these compounds either by palladium-catalyzed cross-couplings or by oxidations of the 4-methyl groups of the pyrimidine subunits. Although the yields for the crucial initial multicomponent reactions leading to the bis(β-methoxy-β

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• bromides rather than expensive iodides and using 4 or propiolic acid rather than TMS-acetylene as inexpensive alkyne sources are described. Keywords: alkynes; decarboxylative couplings; Erlotinib; palladium; propiolic acid; Introduction The Sonogashira coupling reaction of aryl or alkenyl halides with

• presence of a Cu/Pd bimetallic catalyst, followed by the basic cleavage of the protecting group [42][43][44][45][46]. Terminal alkynes are often used as starting materials for the synthesis of disubstituted acetylenes through a second coupling process with another aryl halide. Decarboxylative couplings

• coupling) and diaryl diacetylenes (sp–sp coupling) in addition to examples of carbon-heteroatom couplings have been reported in the recent literature [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65]. The convenience in using propiolic acid as the alkyne source in the synthesis

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• tools in synthetic organic chemistry. The most significant recent results and developments obtained in this area are reported in this review. Keywords: allylboration; boron compounds; Diels–Alder; 1,3-dienes; multicomponent reactions; Petasis borono–Mannich; Suzuki couplings; Introduction

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• references [40][41]). The relative configuration of the newly formed stereogenic center at the C-2 position of 13 was successfully determined by NOE experiments. By irradiation of the 2-H proton (Figure 2) several dipolar couplings with 1-H, 4-H and with one proton of the p-bromophenyl group were observed

• (back-side) attack is probably hindered by the bulky OTBS group (also see Scheme 5). The configurational assignments are in accordance with NOE experiments performed with the alcohol derived from ketone 13 (precursor of 16), where dipolar couplings have been observed between the 10-H and 9-H protons

• reduction of the carbonyl group [43] and TBS cleavage, propargylic ether 18 was obtained (88% yield over two steps) [44]. The alkyne moiety provides options for further transformations, e.g. Sonogashira reactions, Glaser couplings or 1,3-dipolar cycloadditions (click reactions) [45]. We were also interested