Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• the main product, but also containing biphenyl, traces of the desired product 6a, the homocoupling dimer 7a as well as a compound 8, obviously resulting from attack of PhLi to the pyridine system attached to pyrazole N-1 (Scheme 4). Negishi cross-couplings with 4-iodopyrazoles 3a–d The Negishi cross

• –halogen exchange and subsequent carboxylation with iodopyrazoles 3a–d. Attempted cross-coupling reactions with 4-halopyrazoles 5 and 3a. Negishi couplings with 4-iodopyrazoles 3a,b. Formation of pyrazoloquinolizin-6-ium iodide 12 upon reaction of 3a with (phenylethynyl)zinc bromide. Prototropic

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• spin system A was established . Two further smaller fragments were established via COSY correlations from H-5 to H-7 (B), and from H-9 to H-11 (C). These subunits could be assigned to a 14-membered cembrane skeleton according to couplings detected in the HMBC experiment. Key heteronuclear long range

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• malonate units. In the 13C NMR spectrum, split signals arising from 13C–13C couplings were observed for six pairs of carbons: C-11/C-12, C-13/C-14, C-15/C-16, C-17/C-18, C-19/C-20, and C-21/C-22 (Table 1, Figure S1 in Supporting Information File 1). In the 2D-INADEQUATE spectrum of 13C-labeled 1 obtained

• investigate this possibility, we conducted a feeding experiment of [U-13C6]glucose which could label carbons derived from malonyl-CoA and hydroxymalonyl-ACP. In the 13C NMR spectrum, 13C–13C couplings were observed for C-1/C-2, C-3/C-4, C-5/C-6, C-7/C-8 in addition to the carbon pairs C-11/C-12, C-13/C-14, C

Decarboxylative and dehydrative coupling of dienoic acids and pentadienyl alcohols to form 1,3,6,8-tetraenes

• Ghina’a I. Abu Deiab,
• Mohammed H. Al-Huniti,
• I. F. Dempsey Hyatt,
• Emma E. Nagy,
• Kristen E. Gettys,
• Sommayah S. Sayed,
• Christine M. Joliat,
• Paige E. Daniel,
• Rupa M. Vummalaneni,
• Andrew T. Morehead Jr,
• Andrew L. Sargent and
• Mitchell P. Croatt

Beilstein J. Org. Chem. 2017, 13, 384–392, doi:10.3762/bjoc.13.41

• . Prior and current decarboxylative couplings. Esters examined in the decarboxylation reaction. Possible mechanistic pathways. Optimization of the one-component decarboxylation reaction.a Optimization of the two-component decarboxylation reaction.a Substrate scope for the two-component decarboxylation

Highly bulky and stable geometry-constrained iminopyridines: Synthesis, structure and application in Pd-catalyzed Suzuki coupling of aryl chlorides

• Yi Lai,
• Zhijian Zong,
• Yujie Tang,
• Weimin Mo,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen,
• Liqun Jin,
• Wen-hua Sun and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 213–221, doi:10.3762/bjoc.13.24

• showed a good catalytic efficiency for both Suzuki and Heck cross-coupling reactions. The favorable effect originated from the ring-fused framework being able to establish a strained environment for better stability. Efficient couplings were achieved with aryl bromides or iodides as substrates, however

Dynamics and interactions of ibuprofen in cyclodextrin nanosponges by solid-state NMR spectroscopy

• Monica Ferro,
• Franca Castiglione,
• Nadia Pastori,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2017, 13, 182–194, doi:10.3762/bjoc.13.21

• couplings [14]. In the opposite case, i.e., when weak I*−S and strong I−I* couplings are present, the CP kinetics follow the more general I−S model. As a final remark, we wish to stress that the oscillatory behaviour described above has not been reported frequently so far, and that the data reported and

• discussed in the following of this work represent an example. Results and Discussion Solid-state NMR 1H MAS NMR spectroscopy 1H high-resolution spectra of small organic molecules, characterised by the isotropic chemical shift and J couplings, are easily obtained in solution. By contrast, for rigid solids

• , the corresponding solid-state 1H NMR spectrum generally shows broad, featureless lines due to the strong homonuclear dipolar couplings among protons, which in many cases exceed the range of chemical shifts. Consequently, solid-state 1H NMR spectra are seldom reported, the assignment of the 1H

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

• unsuccessful. NMR studies of 1 revealed that the compound adopted a skew-boat conformation, based on the small 3J coupling constants, as well as long range w-couplings. This conformational flip is induced by the presence of the bulky trans-vicinal silyl groups [6]. Also with the purpose of having acid-labile

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• coupling. For this purpose, we selected (trimethylsilyl)acetylene as alkyne component. The Sonogashira couplings of 5-iodo-1,2-oxazines syn-4a and anti-4a were carried out under standard conditions using a catalytic system consisting of PdCl2(PPh3)2, CuI and triethylamine in toluene at room temperature to

• transformation was considerably improved when an alternative coupling protocol (Pd(OAc)2, PPh3, CuI in NEt3/DMF) was employed, the yield was significantly enhanced and the coupling product anti-6 was obtained in 59% yield. Sonogashira couplings of 4-benzyloxy- and 4-(2-trimethylsilyl)ethoxy-substituted 1,2

• component in other Sonogashira couplings presented in former publications [23][32]. The reaction of syn-4a and alkyne 10 using palladium acetate, triphenylphosphine, and copper(I) iodide in a solvent mixture of diisopropylamine and DMF at room temperature gave the 5-(imidazolylethynyl)-substituted 1,2

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• the nitrogen atom. As shown by our synthesis, all of these electron acceptor units were tolerant to Sonogashira coupling conditions, which produced new EDOT derivatives 9, 10, 11 and 12 (Scheme 4). The Sonogashira couplings were performed between the alkyne terminal of pyEDOT and a brominated ring

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

• = 749.2 which corresponds to the molecular peak of a [Rh(7)3 + H]+ complex. In the 13C NMR spectra, the Ccarbene resonance frequencies were detected at 173.5 ppm, 171.0 ppm, and 164.4 ppm and have been identified by their 1JRhCcarbene couplings of 35.6 Hz, 35.6 Hz, and 48.5 Hz, respectively. These

Inhibition of peptide aggregation by means of enzymatic phosphorylation

• Kristin Folmert,
• Malgorzata Broncel,
• Hans v. Berlepsch,
• Christopher H. Ullrich,
• Mary-Ann Siegert and
• Beate Koksch

Beilstein J. Org. Chem. 2016, 12, 2462–2470, doi:10.3762/bjoc.12.240

• according to standard Fmoc chemistry using preloaded Fmoc-Leu-NovaSyn®TGA resin (0.3 mmol g−1, Novabiochem). Standard couplings were performed in DMF with Fmoc-amino acids and TBTU (O-(benzotriazole-1-yl)-N,N,N’,N’-tetramethyluronium tetrafluoroborate)/HOBt (1-hydroxybenzotriazole)/DIC (N,N

• ’-diisopropylcarbodiimide) in eight-fold and NaClO4 in ten-fold excess with double couplings of one hour coupling time. Fmoc-Ser(PO(OBzl)OH)-OH was activated with HATU (O-(7-azabenzotriazol-1-yl)-N,N,N’,N’-tetramethyluronium hexafluorophosphate)/HOBt five-fold and fifteen-fold excess of DIPEA (N,N-diisopropylethylamine

• ) with respect to the resin and two hour double couplings. A mixture of DBU (1,8-diazabicyclo[5,4,0]undec-7-ene) and piperidine (2% each) in DMF was used for Fmoc-deprotection (3 × 10 min). The resin was washed between each step with DMF and DCM (3 × 6 mL each). Peptides were cleaved from the resin by

A new paradigm for designing ring construction strategies for green organic synthesis: implications for the discovery of multicomponent reactions to build molecules containing a single ring

• John Andraos

Beilstein J. Org. Chem. 2016, 12, 2420–2442, doi:10.3762/bjoc.12.236

• partitioning to chemical structures. Two problems are addressed: (1) the determination of the total number of possible ways to construct a given ring by 2-, 3-, and 4-component couplings; and (2) the systematic enumeration of those possibilities. The results of the method are illustrated using cyclohexanone

• analysis of ring structures to systematically decompose given ring frameworks via 2-, 3-, and 4-component couplings akin to decomposing an integer into 2-, 3-, and 4-partitions. In this way we may explore the full spectrum of possible ring fragmentations and assess each possibility with respect to our

• the total number of possible 2-, 3-, and 4-partitions. These correspond to all possible 2-, 3-, and 4-component coupling assemblages. The 3- and 4-component couplings are commonly referred to as multicomponent reactions (MCRs). Next, we list and draw out each of these partitions in the form of target

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• Fmoc-D-Thr(TES)-OH on HMPB-NovaPEG resin. Successive couplings afforded peptide 104 (Scheme 23). Esterification with Alloc-Ile-OH and extension of the linear chain using conventional Fmoc SPPS afforded ester-peptide 105. Deprotection of the N-alloc group and coupling of the key L-allo-enduracididine

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• resulting in the formation of the desired triazines 3b and 3c in 53 and 61% yield, respectively. Following the synthetic plan of Figure 3, the tribromides 3b and 3c were used in the Suzuki couplings. In this and respective following synthetic steps, optimization of the reaction conditions was very important

Regiocontroled Pd-catalysed C5-arylation of 3-substituted thiophene derivatives using a bromo-substituent as blocking group

• Mariem Brahim,
• Hamed Ben Ammar,
• Jean-François Soulé and
• Henri Doucet

Beilstein J. Org. Chem. 2016, 12, 2197–2203, doi:10.3762/bjoc.12.210

• also investigated. Under the same reaction conditions, (1 mol % Pd(OAc)2, DMA, KOAc, 80 °C, 2 h) no formation of the desired 2-bromo-5-arylfuran derivative was observed. The main interest to tolerate a C–Br bond at the C2-position on thiophene derivatives in the course of such couplings would be the

Comparing blends and blocks: Synthesis of partially fluorinated diblock polythiophene copolymers to investigate the thermal stability of optical and morphological properties

• Pierre Boufflet,
• Sebastian Wood,
• Jessica Wade,
• Zhuping Fei,
• Ji-Seon Kim and
• Martin Heeney

Beilstein J. Org. Chem. 2016, 12, 2150–2163, doi:10.3762/bjoc.12.205

• around 2.65 ppm are likely related to regiochemical defects such as head-to-head or tail-to-tail couplings in the backbone [43], as well as the methylene region from the chain end [44]. Integration of this region with respect to the overall methylene region gives approximate regioregularites of 92 and 97

Rapid regio- and multi-coupling reactivity of 2,3-dibromobenzofurans with atom-economic triarylbismuths under palladium catalysis

• Maddali L. N. Rao,
• Jalindar B. Talode and
• Venneti N. Murty

Beilstein J. Org. Chem. 2016, 12, 2065–2076, doi:10.3762/bjoc.12.195

• -dibromobenzofuran with arylboronic acids under palladium catalyzed conditions [29][30]. Bach et al. reported site-selective studies involving the Sonogashira, Negishi, Kumada cross-couplings employing 2,3-dibromobenzofuran and 2,3,5-tribromobenzofuran substrates [31][32][33]. Additionally, Langer et al. reported

• bromobenzofurans were not reported so far (Scheme 1) [35]. Given the importance of threefold couplings’ reactivity realized with the sub-stoichiometric loading of triarylbismuths in the cross-coupling reactions [35][36][37][38][39][40][41][42], we report herein, a novel regio- and multi-coupling of

• -dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) furnished lowered yields (Table 1, entries 6 and 7) in comparison with NMP solvent. Carrying out the cross-couplings at different temperatures also gave lower yields (Table 1, entries 8 and 9). Additionally, the stoichiometric combination of 3 equiv of 2,3

Application of heterocyclic aldehydes as components in Ugi–Smiles couplings

• Katelynn M. Mason,
• Michael S. Meyers,
• Abbie M. Fox and
• Sarah B. Luesse

Beilstein J. Org. Chem. 2016, 12, 2032–2037, doi:10.3762/bjoc.12.191

• Katelynn M. Mason Michael S. Meyers Abbie M. Fox Sarah B. Luesse Department of Chemistry, Southern Illinois University Edwardsville, Edwardsville, Illinois 62026, USA 10.3762/bjoc.12.191 Abstract Efficient one-pot Ugi–Smiles couplings are reported for the use of furyl-substituted aldehyde

• and have inspired the development of new multicomponent coupling reactions. Isocyanide-based multicomponent couplings [1], led by the foundational Ugi four-component coupling [2][3], have been used extensively for the synthesis of natural products and the preparation of diverse heterocyclic scaffolds

• couplings in combination with post-condensation processes to efficiently increase structural complexity [8][9][10]. One of the most effective routes to polycyclic core structures uses intramolecular Diels–Alder reactions (IMDA) of tethered, substituted furans to provide stereoselective construction of

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• -rich (65% yield) and electron-poor (38% yield) 2-substituted phenylboronic acids, most likely due to steric factors (31 and 35, Scheme 2). It is noteworthy that for all of the 3-phenyl-1H-pyrazole couplings, only the 1,3-disubsituted pyrazole products were obtained with no 1,5-disubsituted isomers

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• -bromo-1,1-dimethylindene. Keywords: base-free dehydrobromination; cis/trans stereochemistry; five-membered ring conformation; indenes; NMR couplings; Introduction The basic mechanistic features of competing suprafacial and antarafacial additions of elemental bromine to an olefin are reasonably well

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• couplings. Thus, a library of specifically substituted bipyridine derivatives was generated, showing the versatility of the simple 1,3-diketone-based approach to this important class of ligands. Keywords: 2,2-bipyridines; cross couplings; cyclocondensation; β-ketoenamides; nonaflates; Introduction In 2009

• the corresponding N-oxide 8. Suzuki-couplings of 2,2'-bipyrid-4-yl nonaflates 5a and 5b to compounds 9 and 10. Palladium-catalyzed couplings of chloro-substituted 2,2'-bipyrid-4-yl nonaflate 5g leading to compounds 11, 12 and 13. Attempted TMSOTf/DIPEA-promoted cyclocondensations of β-ketoenamides 3a

Cationic Pd(II)-catalyzed C–H activation/cross-coupling reactions at room temperature: synthetic and mechanistic studies

• Takashi Nishikata,
• Alexander R. Abela,
• Shenlin Huang and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2016, 12, 1040–1064, doi:10.3762/bjoc.12.99

• electrophilic palladation step, potentially gaining entry to C–H activation under even milder reaction conditions for selected couplings than have previously been observed (Scheme 1, bottom) [120][121][122]. Metal cations, in general, are well known to increase the reactivity of C–C and C–N double bonds due to

A convenient route to symmetrically and unsymmetrically substituted 3,5-diaryl-2,4,6-trimethylpyridines via Suzuki–Miyaura cross-coupling reaction

• Dariusz Błachut,
• Joanna Szawkało and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2016, 12, 835–845, doi:10.3762/bjoc.12.82

• ), reaction conditions (the nature of the palladium/ligand, temperature, base, solvents) and the steric interactions between both cross-coupling partners. Minard et al. [59] pointed out that if an arylboronic acid involved in sequential couplings bears substituents with electron-withdrawing and electron

• construction of unsymmetrically arylated pyrroles, thiophenes and 2,6- and 3,5-diarylpyridines. In order to test the utility of the above mentioned approach, a series of trial cross couplings were performed on a microscale according to route 3 with a variety of electron-poor and electron-rich boronic acids

• diarylpyridines 46–56, directly from 1 by two sequential cross couplings with the isolation and full characterization of the intermediates 3 and 43–45. Thus, the treatment of 1 with 1.1 equiv of phenyl-, 2-methylphenyl-, 4-methylphenyl and 2-naphthylboronic acid in dioxane in the presence of PdCl2(dppf) × CH2Cl2

Elucidation of a masked repeating structure of the O-specific polysaccharide of the halotolerant soil bacteria Azospirillum halopraeferens Au4

• Elena N. Sigida,
• Yuliya P. Fedonenko,
• Alexander S. Shashkov,
• Nikolay P. Arbatsky,
• Evelina L. Zdorovenko,
• Svetlana A. Konnova,
• Vladimir V. Ignatov and
• Yuriy A. Knirel

Beilstein J. Org. Chem. 2016, 12, 636–642, doi:10.3762/bjoc.12.62

• calibration. Two-dimensional NMR experiments were performed using standard Bruker software. Spin lock time in TOCSY experiments and mixing time in ROESY experiments were set to 60 and 200 ms, respectively. The HMBC spectrum was recorded with a 60-ms delay for evolution of long-range couplings. Samples were

cis–trans-Amide isomerism of the 3,4-dehydroproline residue, the ‘unpuckered’ proline

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2016, 12, 589–593, doi:10.3762/bjoc.12.57

• . Previously we speculated that the CF3-group in 3 should adopt an equatorial conformation, and thus stabilize the exo-pucker, based upon considerations of the vicinal J-couplings (in Ac-TfmPro-OMe, 7) [35]. Considering that the CF3-substituent should be located within the plane of the 3-pyrroline ring in 4