Hexacoordinate Ru-based olefin metathesis catalysts with pH-responsive N-heterocyclic carbene (NHC) and N-donor ligands for ROMP reactions in non-aqueous, aqueous and emulsion conditions

• Shawna L. Balof,
• K. Owen Nix,
• Matthew S. Olliff,
• Sarah E. Roessler,
• Arpita Saha,
• Kevin B. Müller,
• Ulrich Behrens,
• Edward J. Valente and
• Hans-Jörg Schanz

Beilstein J. Org. Chem. 2015, 11, 1960–1972, doi:10.3762/bjoc.11.212

• complexes now contain pH-responsive groups at the H2ITap ligand to afford solubility in aqueous acid and at the N-donor ligand which affords rapid metathesis initiation. It should be noted that Plenio et al. also reported a Ru–benzylidene complex similar to catalysts 11 and 12 bearing the NEt2-analogue to

• on the observed reactivity trend from the previous kinetic experiments, it is not surprising that benzylidene complex 11 exhibited a superior performance in aqueous HCl where complex 12 failed to produce noticeable amounts of ring-closed product. Interestingly however, when the aqueous solvent is

• of benzylidene(1,3-bis(2’,6’-dimethyl-4’-dimethylaminophenyl)-2-dihydroimidazolidinylidene)bis(4-dimethylaminopyridine)dichlororuthenium(II) (DMAP)2Cl2(H2ITap)Ru=CHPh (11): 4-Dimethylaminopyridine (DMAP, 315 mg, 2.58 mmol) was added to a slurry of (PCy3)Cl2(H2ITap)Ru=CHPh (10, 987 mg, 1.09 mmol) in

New aryloxybenzylidene ruthenium chelates – synthesis, reactivity and catalytic performance in ROMP

• Patrycja Żak,
• Szymon Rogalski,
• Mariusz Majchrzak,
• Maciej Kubicki and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2015, 11, 1910–1916, doi:10.3762/bjoc.11.206

• donating and electron withdrawing substituents at the benzylidene ligand in para position to the coordinating oxygen and bearing instead of a strong sigma-donor ligand – tricyclohexylphosphine a weaker sigma-donor – a triphenylphosphine ligand or its derivatives. The catalytic performance of the

• 1 h when using monomer to catalyst ratio equal to 2000. Conclusion Ruthenium–benzylidene complexes bearing a triphenylphosphine ligand or its para-substituted analogues undergo metathetic exchange with 2-(prop-1-enyl)phenol or substituted 2-vinylphenols to form phenoxybenzylidene ruthenium chelates

Profluorescent substrates for the screening of olefin metathesis catalysts

• Raphael Reuter and
• Thomas R. Ward

Beilstein J. Org. Chem. 2015, 11, 1886–1892, doi:10.3762/bjoc.11.203

• Grubbs-type catalysts with either a benzylidene ligand or an indenylidene ligand. As a model reaction, we selected ring-closing metathesis and developed two profluorescent substrates that yield a fluorescent product upon ring-closing metathesis (Scheme 1). Substrate 5 consists of a fluorescent 5

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• heterogenize catalysts, which resulted in the formation of materials with reduced activity and efficiency [23][24]. It is well recognized that the benzylidene ligand structure strongly influences initiation rates for Hoveyda-type catalysts [25]. As a consequence of the “boomerang effect”, which was recently

• strongly supported by Fogg et al. [26], the benzylidene ligand also most likely affects propagation rates. In our search for active, more robust and selective catalysts, we synthesized iodide-containing nitro-Grela type catalysts. A synergistic effect of the ligands was sought: the nitro-substituted

• benzylidene ligand was expected to ensure fast initiation, while the bulky iodides were anticipated to provide additional stabilization of the active species. Results and Discussion The new iodide-containing catalysts, nG-I2 and nG-SIPr-I2, were prepared with a 93% yield from commercially available complexes

Cross-metathesis of polynorbornene with polyoctenamer: a kinetic study

• Yulia I. Denisova,
• Maria L. Gringolts,
• Alexander S. Peregudov,
• Liya B. Krentsel,
• Ekaterina A. Litmanovich,
• Arkadiy D. Litmanovich,
• Eugene Sh. Finkelshtein and
• Yaroslav V. Kudryavtsev

Beilstein J. Org. Chem. 2015, 11, 1796–1808, doi:10.3762/bjoc.11.195

• -stage model. At the first stage of the reaction all Ru-benzylidene carbenes are transformed into Ru-polyoctenamers within an hour, while the polymer molar mass is considerably decreased. The second stage actually including interpolymeric reactions proceeds much slower and takes one day or more to

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C–H(sp²)/C–H(sp) coupling under mild conditions

• Wei Zhu,
• Bao Wang,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 1624–1631, doi:10.3762/bjoc.11.177

• hydrazine hydrate and sodium hydroxide. Results and Discussion We initiated our investigation of the direct carbon–carbon coupling of N-(quinolin-8-yl)benzamide (1a) and phenylacetylene (2a). After extensive attempts, 3-benzylidene-2-(quinolin-8-yl)isoindolin-1-one (3a) was formed in 18% yield via the

• mixture was washed with water (3 times) and brine. The combined organic layer was dried with Na2SO4, concentrated, and purified by column chromatography on silica gel (DCM/MeOH 200:1–50:1) to give (Z)-3-benzylidene-2-(quinolin-8-yl)isoindolin-1-one (3a) as a pale yellow solid (81%). General procedure for

• the synthesis of phthalazin-1(2H)-one 4 and recovery of quinolin-8-amine (DG): The synthesis of 4a is representative. The microwave tube was charged with (Z)-3-benzylidene-2-(quinolin-8-yl)isoindolin-1-one (3a, 50 mg, 0.144 mmol), hydrazine hydrate (75 µL, 1.44 mmol), sodium hydroxide (57 mg, 1.44

Latent ruthenium–indenylidene catalysts bearing a N-heterocyclic carbene and a bidentate picolinate ligand

• Thibault E. Schmid,
• Florian Modicom,
• Adrien Dumas,
• Etienne Borré,
• Loic Toupet,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 1541–1546, doi:10.3762/bjoc.11.169

• ][19]. Nevertheless, indenylidene complexes, that have notably showed an improved stability in comparison to their benzylidene counterparts [20][21][22], have never been considered in association with picolinic ligands for the synthesis of robust latent catalysts. Moreover, this strategy would provide

Ruthenium indenylidene “1^st generation” olefin metathesis catalysts containing triisopropyl phosphite

• Stefano Guidone,
• Fady Nahra,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2015, 11, 1520–1527, doi:10.3762/bjoc.11.166

• halides. The apex of the pyramid is occupied by an alkylidene moiety, such as a benzylidene or an indenylidene. Mixed NHC/phosphine complexes (G-II and Ind-II) known as “2nd generation” pre-catalysts generally display higher catalytic activity than “1st generation” complexes (G-I and Ind-I) containing two

• -donor ligand NHC and the π-acidic triisopropyl phosphite [25][37]. Subsequently, the benzylidene analogue G-II-P(OiPr)3 was also reported. The latter displayed a typical trans-configuration, seen in other Ru pre-catalysts, and gave a similar catalytic activity to that of the phosphine-containing parent

Thermal properties of ruthenium alkylidene-polymerized dicyclopentadiene

• Yuval Vidavsky,
• Yotam Navon,
• Yakov Ginzburg,
• Moshe Gottlieb and
• N. Gabriel Lemcoff

Beilstein J. Org. Chem. 2015, 11, 1469–1474, doi:10.3762/bjoc.11.159

• resting periods the crucible was stored at room temperature under ambient conditions unless otherwise noted. DCPD (1) and ruthenium benzylidene catalyst 2. Top: DSC plot of PDCPD 24 hours after polymerization. Blue line: 1st heating–cooling cycle. Black line: 2nd cycle. Bottom: DSC of PDCPD sample after

Consequences of the electronic tuning of latent ruthenium-based olefin metathesis catalysts on their reactivity

• Karolina Żukowska,
• Eva Pump,
• Aleksandra E. Pazio,
• Krzysztof Woźniak,
• Luigi Cavallo and
• Christian Slugovc

Beilstein J. Org. Chem. 2015, 11, 1458–1468, doi:10.3762/bjoc.11.158

• basic structure of ruthenium-based olefin metathesis catalysts led to a diversification of catalytic profiles (Figure 1) [5][6]. Perhaps the most important one was the introduction of bidentate benzylidene ligands instead of simple alkylidenes, thus giving rise to the class of Hoveyda-type complexes

• with the parent compound 2 [7]. Further modifications of such systems followed. One of the most common is tuning of the properties of the benzylidene ligand so that modified reactivity of the resulting complex is achieved [8]. Various examples of such approaches have been published over the years

• species (TS1trans) is considerably lower compared to 5a. These results go in hand with studies on electronically modified Hoveyda-type catalysts [28][29] and electronically modified ester-chelating benzylidene complexes [30]. Moreover, as already discussed, TS2 becomes energetically more demanding so that

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• , with the structure and stereochemistry confirmed by X-ray crystallography. The two others were obtained during a total synthesis of erythronolide Al [55][56], as a result of deprotection of the 3,5-benzylidene acetal of erythronolide A (with or without a triethylsilyl protecting group on 6-O). However

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• TBS group at O-4''' in 59% yield [22]. The excess amount of pyridine is necessary in order to avoid cleavage of the benzylidene acetals. Following the same concept, fully protected hexasaccharide 7 was synthesized. Therefore, thioglycoside 4 was activated with NIS and TfOH and subsequently combined

• reducing conditions (Zn, AcOH) [28] and subsequently the liberated amino groups were acetylated to furnish compound 8. Eventually, the silyl group and all benzylidene moieties were removed by treatment with Olah's reagent to give, after acetylation, derivative 9. Finally, oxidation of the terminal olefinic

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• three-component Biginelli condensation of 3-oxo esters, aldehyde and 5-AT [17][18] or its modification starting from 2-benzylidene-3-oxo esters and 5-AT [19][20]. It may be expected that the use of 5-AT as a nucleophile in the reactions with 2-ethoxymethylidene-3-oxo esters will alter the traditional

Synthesis and biological evaluation of a novel MUC1 glycopeptide conjugate vaccine candidate comprising a 4’-deoxy-4’-fluoro-Thomsen–Friedenreich epitope

• Manuel Johannes,
• Maximilian Reindl,
• Bastian Gerlitzki,
• Edgar Schmitt and
• Anja Hoffmann-Röder

Beilstein J. Org. Chem. 2015, 11, 155–161, doi:10.3762/bjoc.11.15

• ’-fluoro-TF SPPS building block 11 started by conversion of peracetylated D-glucose 1 into β-thio-glycoside 2 [45][46] under Lewis acid catalysis in 81% yield (Scheme 1). Subsequent Zemplén deacetylation [47], followed by 4,6-benzylidene acetal formation and acetylation provided fully protected precursor 3

• [48] in excellent 85% yield over three steps. Acid-catalyzed 4,6-benzylidene deprotection and 6-O-tritylation then afforded alcohol 5 (83% over two steps), which was further converted into an intermediate triflate for subsequent nucleophilic fluorination with TBAF to provide the 4-fluorothioglycoside

Synthesis and characterization of pH responsive D-glucosamine based molecular gelators

• Navneet Goyal,
• Hari P. R. Mangunuru,
• Bargav Parikh,
• Sonu Shrestha and
• Guijun Wang

Beilstein J. Org. Chem. 2014, 10, 3111–3121, doi:10.3762/bjoc.10.328

• for soft biomaterials. Low molecular weight hydrogelators are especially useful for exploring biomedical applications. Previously, we found that 4,6-O-benzylidene acetal protected D-glucose and D-glucosamine are well-suited as building blocks for the construction of low molecular weight gelators. To

• ]. Previously we mostly focused on the modification of the C-2 position of the benzylidene acetal protected headgroups 1 and 2 (Figure 1). We obtained the general structural requirements for acyl derivatives at the 2-position. In this study, we explore the substituent effect at the benzylidene acetal protective

• of the headgroup of this class of LMWGs lays the basis for the design of organo/hydrogelators with desired functionalities. The p-methoxybenzylidene acetal is more pH responsive in comparison to the benzylidene acetal protective group. The p-methoxybenzylidene acetal can be cleaved in the presence of

Synthesis of the pentasaccharide repeating unit of the O-antigen of E. coli O117:K98:H4

• Pintu Kumar Mandal

Beilstein J. Org. Chem. 2014, 10, 2724–2728, doi:10.3762/bjoc.10.287

• center; (d) glycosylation and removal of the p-methoxybenzyl (PMB) group in one-pot. Treatment of p-methoxyphenyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-β-D-galactopyranoside (7) [24] (prepared from D-galactosamine hydrochloride in six steps) with acetic anhydride in pyridine followed by regioselective

• reductive opening of the benzylidene acetal on treatment with sodium cyanoborohydride in the presence of HCl/Et2O [25] furnished p-methoxyphenyl 3-O-acetyl-6-O-benzyl-2-deoxy-2-phthalimido-β-D-galactopyranoside (5) in 77% yield over two steps (Scheme 1). Trisaccharide acceptor 11 could be synthesized

• % yield. NMR spectroscopy confirmed the formation of compound 8 [δ 5.04 (d, J = 3.6 Hz, 1H, H-1B), 4.38 (d, J = 7.6 Hz, 1H, H-1A) in 1H NMR and at δ 103.9 (C-1A), 100.5 (C-1B) in 13C NMR spectra]. Following an earlier report [28], cleavage of the benzylidene acetal from compound 8 catalyzed by perchloric

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

• (−5.51). [5-Nitro-2-(2-phenyl-2,3-dihydro-1,4-benzoxazepin-4(5H)-yl)benzylidene]propanedinitrile (7c): To the stirred solution of rac-5 (100 mg, 0.27 mmol) in chloroform (5 mL), anhydrous MgSO4 (150 mg, 1.25 mmol) and malononitrile (130 mg, 1.97 mmol) were added and the mixture was refluxed for 10 h

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• derivative very similar to 5 but protected as a 4,6-O-benzylidene acetal also led to an anomeric mixture, suggesting that conformational factors might be also involved. In addition, the treatment of this mixture with salicylchlorophosphite produced a mixture of anomeric H-phosphonates, indicating that no

De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• . Results and Discussion The syntheses of 5 and 6 (Scheme 1) generally followed a ring closing metathesis (RCM) strategy that had been established previously [9]. C4,C6-O-Benzylidene-protected allyl glucoside 7, as a mixture of α- and β-anomers, was the starting material for the synthesis. In the first step

• remainder of the synthesis separately. Transacetalization of the C4,C6-O-benzylidene protecting group in methanol provided diols 9a and 9b, respectively in nearly quantitative yields. Chemoselective, DCC-mediated acylation of the primary alcohol group of 9a and 9b at 0 °C with pentenoic acid gave 10a (58

Chemistry of polyhalogenated nitrobutadienes, 14: Efficient synthesis of functionalized (Z)-2-allylidenethiazolidin-4-ones

• Viktor A. Zapol’skii,
• Jan C. Namyslo,
• Mimoza Gjikaj and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2014, 10, 1638–1644, doi:10.3762/bjoc.10.170

• out a Knoevenagel-type condensation with benzaldehyde and 3,4-dichlorobenzaldehyde in acetic acid at 118 °C in the presence of triethylamine. Thus, the 5-arylmethylidenethiazolidin-4-ones 22–26 were obtained in 68–94% yield. The presence of only one signal for the benzylidene proton at 7.83–7.98 ppm

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• the A-band polysaccharide of Pseudomonas aeruginosa. One of the key steps involved 6-O-deoxygenation of either partially or fully acylated 4,6-O-benzylidene-1-thiomannopyranoside by radical-mediated redox rearrangement in high yields and regioselectivity. The D-rhamno-thioglycosides so obtained

• allowed efficient access to the trisaccharide target via stepwise glycosylation as well as a one-pot glycosylation protocol. In a different approach, a 4,6-O-benzylidene D-manno-trisaccharide derivative was synthesized, which upon global 6-O-deoxygenation followed by deprotection generated the target D

• -rhamno-trisaccharide. The application of the reported regioselective radical-mediated deoxygenation on 4,6-O-benzylidene D-manno thioglycoside (hitherto unexplored) has potential for ramification in the field of synthesis of oligosaccharides based on 6-deoxy hexoses. Keywords: A-band polysaccharide; D

Design, automated synthesis and immunological evaluation of NOD2-ligand–antigen conjugates

• Marian M. J. H. P. Willems,
• Gijs G. Zom,
• Nico Meeuwenoord,
• Ferry A. Ossendorp,
• Herman S. Overkleeft,
• Gijsbert A. van der Marel,
• Jeroen D. C. Codée and
• Dmitri V. Filippov

Beilstein J. Org. Chem. 2014, 10, 1445–1453, doi:10.3762/bjoc.10.148

• attached to the anomeric center of the glucosamine moiety using oxazoline 6 [37][38][39]. Deacetylation and subsequent installation of the benzylidene protective group then gave alcohol 9. Coupling of 9 with (S)-2-chloropropanoic acid in the presence of sodium hydride resulted in the formation of protected

• was removed with Bu3SnH and Pd(PPh3)4 under acidic conditions yielding compound 16 in 72% [42]. For the immunological evaluation of conjugates 2–5 relevant reference compounds are needed, and to this end we assembled MDP derivative 20. On paper, acidic removal of the Boc and benzylidene protecting

• groups in 14 could lead to reference compound 20 in a single step. However, treatment of 14 with a solution of 20% TFA in DCM was accompanied by hydrolysis of the glycosidic linkage. To suppress acid-mediated hydrolysis a stepwise deprotection procedure was followed in which the benzylidene group was

Olefin cross metathesis based de novo synthesis of a partially protected L-amicetose and a fully protected L-cinerulose derivative

• Bernd Schmidt and
• Sylvia Hauke

Beilstein J. Org. Chem. 2014, 10, 1023–1031, doi:10.3762/bjoc.10.102

• better results were obtained with two different phosphine free catalysts comprising a hemilabile alkoxy substituted benzylidene ligand, even at only moderately elevated temperatures. The acrolein cross metathesis product can be converted into the 4-benzoate of L-amicetose via benzoylation, Pd-catalyzed

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• study the course of this cycloaddition the two low molecular model nitrones methyl 3-[benzylidene(oxido)amino]propanoate (3a) and methyl 3-[benzylidene(oxido)amino]butanoate (3b), were prepared from methyl acrylate (2a) and methyl crotonate (2b) with E-benzaldoxime (1) (Scheme 1), respectively. The

• methyl 3-[benzylidene(oxido)amino]propanoate (3a): Methyl acrylate (2a, 0.86 g, 10 mmol) and benzaldoxime (1, 2.42 g, 20 mmol) were placed in a 100 mL round bottom flask and dissolved in 20 mL toluene. Zinc iodide (0.32 g, 1 mmol) and boron triflouride diethyl etherate (0.30 g, 1 mmol) were added. The

• ]. Synthesis of methyl 3-[benzylidene(oxido)amino]butanoate (3b): Methyl crotonate (2b, 1 g, 10 mmol) and benzaldoxime (1, 2.42 g, 20 mmol) were placed in a 100 mL round bottom flask and dissolved in 40 mL toluene. Zinc iodide (0.48 g, 1.5 mmol) and boron triflouride diethyl etherate (0.44 g, 1.5 mmol) were

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• same reaction with benzylidene or isopropylidene glucals resulted in a complex mixture of products and the desired product was not isolated. Furthermore, the scope of this reaction was extended by subjecting glycals to reactions with other nucleophiles. Thus, glycals 1a and 1b subjected to treatment