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

A unified approach to the important protein kinase inhibitor balanol and a proposed analogue

• Tapan Saha,
• Ratnava Maitra and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2013, 9, 2910–2915, doi:10.3762/bjoc.9.327

• generation catalyst, benzylidene[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro-(tricyclohexylphosphine)ruthenium (25). Pleasingly, the desired cycloalkene 26 was obtained in a gratifying yield of 89%. The sequential removal of the O-acetyl group leading to 27 followed by removal of the N-Boc

IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• synthesis of novel [1,2,4]triazolo[1,5-a]pyrimidine derivatives by iodobenzenediacetate (IBD)-mediated oxidative cyclization of suitable N-benzylidene-N′-pyrimidin-2-yl hydrazine precursors, followed by a Dimroth rearrangement [20]. We envisioned that our aldehyde chloropyrimidinylhydrazones 4 would undergo

The total synthesis of D-chalcose and its C-3 epimer

• Jun Sun,
• Song Fan,
• Zhan Wang,
• Guoning Zhang,
• Kai Bao and
• Weige Zhang

Beilstein J. Org. Chem. 2013, 9, 2620–2624, doi:10.3762/bjoc.9.296

• deprotected and oxidized to yield the corresponding aldehyde. Our first step toward this goal was to select appropriate protective groups. Diol 6 was initially converted into benzylidene derivative 8 (α,α-dimethoxytoluene/PPTS/CH2Cl2); 8 was subjected to a regioselective reductive ring-opening reaction [23

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• crude material in the subsequent Knoevenagel condensation with thiazolidinedione 1.68. In order to reduce the intermediate benzylidene double bond in this example sodium borohydride is used in the presence of cobalt chloride efficiently delivering pioglitazone in high purity. Other syntheses of

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• 25); Si: SiMe2Ph, SiMe2Bn (2.0 equiv of 25). Silyl ether synthesis and domino carbopalladation reaction. R,R (Glc): isopropylidene. R,R (Gal): benzylidene. aThe respective equivalents of alkynes 16, glycals 15 and bromine as well as reaction times are given in the Experimental. bThe reaction was

• performed according to entry 5 of Table 1. Derivatisation of anthracycline derivatives. aR,R (Glc): isopropylidene. R,R (Gal): benzylidene. Reactions times: b1.5 h (Glc), 3.5 h (Gal). c1.0 h (Glc), 4.0 h (Gal). d38 h (Glc), 86 h (Gal). e4.0 h (Glc), 3.0 h (Gal). f14 h (Glc), 17 h (Gal). Optimization study

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• %) to yield final targets 2 and 3 in 60% and 70% yield, respectively (Scheme 1). Access to branched core 2 trisaccharide 4 was accomplished by 4,6-O-benzylidene acetal cleavage from disaccharide 15 using a modified procedure from Chang et al. [21] whereby reaction with p-TsOH in MeOH under sonication

• peracetylated trichloroacetimidate donor 13 in the presence of catalytic TMSOTf. Disaccharide 24 was obtained in 62% yield and without any further protecting-group manipulations, the thioglycoside disaccharide was subsequently activated as a glycosyl donor using NIS/TMSOTf and coupled to 4,6-O-benzylidene

• cleavage of the 4,6-O-benzylidene acetals using p-TsOH in MeOH under sonication followed by removal of the N-Troc groups in the presence of LiOH and subsequent acetylation with pyridine and acetic anhydride formed the desired acetamido functionalities, removal of the ester groups under basic conditions was

Raman spectroscopy as a tool for monitoring mesoscale continuous-flow organic synthesis: Equipment interface and assessment in four medicinally-relevant reactions

• Trevor A. Hamlin and
• Nicholas E. Leadbeater

Beilstein J. Org. Chem. 2013, 9, 1843–1852, doi:10.3762/bjoc.9.215

• )-ethyl 2-benzylidene-3-oxobutanoate (2a, 1.3095 g, 60%) as a clear yellow oil. 1H NMR (CDCl3, 400 MHz) δ ppm 1.26 (t, J = 7.21 Hz, 3H), 2.41 (s, 3H), 4.32 (q, J = 7.09 Hz, 2H), 7.33–7.41 (m, 3H), 7.42–7.47 (m, 2H), 7.56 (s, 1H); 13C NMR (CDCl3, 100 MHz) δ ppm 14.08 (CH3), 26.74 (CH3), 61.92 (CH2), 129.06

• 1608 cm-1 vs concentration of 3-acetyl coumarin (1), yielding a straight line, y = mx + b; m = Raman intensity·M−1 of 1. Monitoring the conversion of benzaldehyde and ethyl acetoacetate to (Z)-ethyl 2-benzylidene-3-oxobutanoate (2a) across a range of reaction conditions (scan time = 15 s, integration

• )-one (4a) across a range of reaction conditions (scan time = 15 s, integration = 10 s). The reaction between salicylaldehyde and ethyl acetoacetate to form 3-acetyl coumarin (1). The Knoevenagel condensation of benzaldehyde and ethyl acetoacetate to yield (Z)-ethyl 2-benzylidene-3-oxobutanoate (2a