SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• distinguished these alcohols by selective protection of the OH-7 functionality as 2,7-anhydro-Neu5Ac, leaving position OH-4 free for glycosylation upon protection of the vicinal OH-8 and OH-9 substituents as benzylidene or acetonide rings [6]. The formation of the bicyclo[3.2.1] backbone of 2,7-anhydro-Neu5Ac

• (Scheme 5). However, the desired acetolysis products 30, 34, and 38 were not obtained. Replacing the more reactive fucose moiety and the benzylidene acetal ring of 29, i.e., using the less reactive complement 33, was also unsuccessful. The branched fucose, benzylidene, and isopropylidene rings of the

Design, synthesis and investigation of water-soluble hemi-indigo photoswitches for bioapplications

• Daria V. Berdnikova

Beilstein J. Org. Chem. 2019, 15, 2822–2829, doi:10.3762/bjoc.15.275

• insoluble precipitate of indigo side-product. After filtration, the solvent was partially removed and the pure Z-isomer of the corresponding product was crystallized at −20 °C. (Z)-2-(4-(Dimethylamino)benzylidene)indolin-3-one (Z-1a) Deep violet needles, yield 86% (259 mg, 0.98 mmol); mp 232–234 °С (lit

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• the target molecule. First, the phthalimido group was removed using ethylenediamine [26] followed by acetylation with Ac2O in the presence of pyridine [27] to furnish the desired acetamido functionality. Next, the benzylidene group was hydrolyzed using 80% AcOH at 80 ºC [28]. Further, Zemplén de-O

A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes

• Joza Schmitt and
• Scott T. Handy

Beilstein J. Org. Chem. 2019, 15, 1781–1785, doi:10.3762/bjoc.15.171

• of snapdragons and cosmos. Most studies of aurones focus on their range of biological activities, but relatively little has been reported with respect to their optical properties, unlike their aza and thio analogs. What little is known has focused entirely on the influence of the benzylidene portion

• limited in scope to the influence of the benzylidene portion. Most noteworthy is the report by Bane and co-workers examining the UV–vis and fluorescent properties of a series of amino-substituted aurones [4]. Subsequently, Liu and co-workers explored the same series of aurones using computational methods

• benzofuranone and methoxy moiety and one methoxy/bromo-substituted benzylidene group, but none in which the benzofuranone was unsubstituted (see Figure 1 for numbering) [6]. This meant that no comparison regarding the influence of substitution could realistically be made. They did observe that a methoxy group

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• [19], again with 5 equiv of reagent, afforded the cyclic boronic acid 10 in a fair yield. Benzylidene group hydrogenolysis gave the deprotected pure cyclic boronic acid 11 in quantitative yield and compound 11 proved to be stable for months. In this case the elimination reaction was not observed as

• around the boron atom. Compound 8 shows two isochronal protons at C-2 with a J2,3 = 4.9 Hz, and superposition of protons H-3 and H-5 not allowing to hypothesize a clear picture of the 6-membered ring conformation. Concerning compound 10, the molecule is rigid around the benzylidene ring, while a

• broadening of the H-2, H-3 and H-4 signals suggest a slow equilibrium between different conformations. After deprotection of the benzylidene group in addition to line broadening, signal superposition is observed, hampering any conclusion on the conformation of compound 11. In order to get more information

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• -dihydropyridine 46 fused to the androstane at positions 16 and 17 (Scheme 14). The MCR proceeds by the condensation of malononitrile with benzaldehyde to form the benzylidene malononitrile adduct, and of the ketosteroid with ammonium to form the steroidal enamine, which cyclizes with the benzylidene to furnish

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• H2O (ca. 6%) severely affects the phosphine-based catalysts Caz-I and Ind-II, while it has a less pronounced detrimental effect on the isopropyloxy-benzylidene catalyst HG-II. “On water” vs “in water” metathesis Hydrophobic catalysts are able to perform metathesis in aqueous mixtures. Blechert and

• the benzylidene moiety, such as NO2 [58], they proposed an “electron-donating to electron-withdrawing activity switch”, consisting of an in situ formation of quaternary ammonium salts by treatment with Brønsted acids (Scheme 10). Several metathesis reactions were performed in methanol/water mixtures

Convergent synthesis of the pentasaccharide repeating unit of the biofilms produced by Klebsiella pneumoniae

• Arin Gucchait,
• Angana Ghosh and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2019, 15, 431–436, doi:10.3762/bjoc.15.37

• -azidoethyl 4,6-O-benzylidene-β-D-glucopyranoside (8) [18], prepared from D-glucose, was selectively O-allylated at the 3-hydroxy group by treatment with dibutyltin oxide followed by allyl bromide in the presence of cesium fluoride [19] via the formation of a stannylene acetal to give 2-azidoethyl 3-O-allyl

• -4,6-O-benzylidene-β-D-glucopyranoside (9). Compound 9 was treated with benzyl bromide in the presence of sodium hydride [20] to give O-benzylated derivative 10 in 90% yield in two steps, which on de-O-allylation by treatment with palladium chloride [21] furnished 2-azidoethyl 2-O-benzyl-4,6-O

• -benzylidene-β-D-glucopyranoside (11) in 70% yield. Stereoselective glycosylation of compound 11 with D-mannose-derived ethyl 2-O-acetyl-3,4,6-tri-O-benzyl-1-thio-α-D-mannopyranoside (3) [14] in the presence of a combination of N-iodosuccinimide (NIS) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) [22

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• substituent at C1. Whereas conjugation with the phenyl group (R = Ph) provides the driving force for the base-promoted isomerization of 1-benzyl-3,3-difluorocyclopropene (A’, R = Ph) into the corresponding benzylidene(gem-difluoro-cyclopropane) (B’) [18], methylene(gem-difluorocyclopropane) (B’’, R = H) is

• or a p-anisyl group, respectively. The rearrangement of imidate 12f possessing a m-anisyl substituent afforded benzylidene cyclopropane 13f in a lower yield (47%) compared to 13d (77%). The rearrangement of imidate 12i possessing an electron-rich N-tosylpyrrol-2-yl heteroaromatic group, afforded

Application of olefin metathesis in the synthesis of functionalized polyhedral oligomeric silsesquioxanes (POSS) and POSS-containing polymeric materials

• Patrycja Żak and
• Cezary Pietraszuk

Beilstein J. Org. Chem. 2019, 15, 310–332, doi:10.3762/bjoc.15.28

• -substituted vinylsilanes with Grubbs catalyst of first or second generation (A), the active methylene complex B and the corresponding (E)-1-phenyl-2-(silyl)ethene are formed. The methylene complex B in the presence of styrene undergoes metathetic conversion to benzylidene complex A and ethene. When dichloro

Catalysis of linear alkene metathesis by Grubbs-type ruthenium alkylidene complexes containing hemilabile α,α-diphenyl-(monosubstituted-pyridin-2-yl)methanolato ligands

• Tegene T. Tole,
• Johan H. L. Jordaan and
• Hermanus C. M. Vosloo

Beilstein J. Org. Chem. 2019, 15, 194–209, doi:10.3762/bjoc.15.19

• and 5d Proton nuclear magnetic resonance spectrometry (1H NMR) is a powerful tool to study ruthenium alkylidene complexes and was used to study 1-octene metathesis in the presence of 1 and 2 [10][21][22]. The conversion of the benzylidene, [Ru]=CHPh, to the heptylidene, [Ru]=CHC6H13, and methylidene

• pyridinyl-alcoholato ligand was in the “closed” (coordinated) position; δCHPh 18.05 ppm, δCHHx 16.71 ppm and δCHH 16.08 ppm [10]. The other two was attributed to the benzylidene (δCHPh 19.48 ppm) and methylidene (δCHH 19.76 ppm) species in the “open” (uncoordinated) position with the uncoordinated

• benzylidene (δ 17.33 ppm, singlet), heptylidene (δ 16.85 ppm, triplet) and methylidene (δ 15.68 ppm) were observed. A small signal at δ 16.66 ppm appeared at 270 min and was not assigned (inter alia multiplicity not discernable). A different development of carbene signals over time is observed than what was

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation

• Łukasz Gułajski,
• Andrzej Tracz,
• Katarzyna Urbaniak,
• Stefan J. Czarnocki,
• Michał Bieniek and
• Tomasz K. Olszewski

Beilstein J. Org. Chem. 2019, 15, 160–166, doi:10.3762/bjoc.15.16

• ionic tag attached to the benzylidene ligand, with that of catalyst 1a, bearing an ionic tag placed on the N-heterocyclic carbene (NHC) fragment. As model reactions we have selected the ring-closing metathesis (RCM) of the water-soluble substrate 6, the homometathesis of alcohol 8, and more challenging

• metathesis transformations in water catalysed by ammonium-tagged Ru-based catalysts. It was noted that placing the water solubilising ionic tag on the NHC ligand gives catalysts with improved catalytic activity and more suitable for reactions in water than those having an ionic tag on the benzylidene part

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• % of TMSOTf with respect to the donor, 0 ºC, CH2Cl2 as solvent). As mentioned before, it has been reported that cyclic protecting groups like 4,6-O-benzylidene acetals in GalNAc trichloroacetimidates lead to the formation of α/β mixtures in glycosylations involving GlcA acceptors [43][47]. However

• , excellent β-stereoselectivity is observed when the benzylidene group is replaced by two acyl groups [43][47]. In the condensation of 1 and 2, an α/β mixture was obtained despite the presence of two acetyls at positions 4 and 6 of the donor. In order to access to final CS sequences ready for biological

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• converted completely within a few hours into complex 2 due to the formation of an intramolecular carbene–arene bond between the benzylidene carbon atom and the ortho position of the N-phenyl ligand (Figure 3). According to the authors, the mechanism of the reaction that occurs only in the presence of oxygen

• improve E/Z selectivity in CM reactions and diastereoselectivity in RCM reactions altering the environment of key metathesis intermediates. Complexes 24 and 25 were found to exist in solution as a single rotational isomer having the benzylidene moiety located under the mesityl group, and for complexes 24b

• to IndII-SIMes. Indeed, besides its faster initiation, complex 41 offers a less encumbered NHC for the approach of substrates to the metal center during the metathesis process. The performance of complex 41 also was compared with that of the benzylidene analogue GII-SIMes in the RCM of 7 (Scheme 1

A tutorial review of stereoretentive olefin metathesis based on ruthenium dithiolate catalysts

• Daniel S. Müller,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2018, 14, 2999–3010, doi:10.3762/bjoc.14.279

• . Therefore, trisubstituted alkenes work best with the same catalysts used for E-alkenes (e.g., Ru-7, Ru-8 and Ru-9). 3 Kinetic studies Grubbs studied the kinetic behavior of several Ru-dithiolate catalysts [6][14][15]. In a typical study the disappearance of the benzylidene proton of the ruthenium complex

• probably catalytically inactive. This assumption is supported by the isolation of ruthenium complex Ru-13 which was formed by nucleophilic attack of a sulfide ligand onto the electron-poor benzylidene ligand [4]. Hoveyda reasoned that replacing the thiocatecholate ligand (Ru-2) by an electron-deficient

• electronically modified ruthenium dithiolate complexes. Model for stereoretentive metathesis proposed by Pederson and Grubbs [3]. Decrease in the benzylidene signal over time upon reaction with (E)-2-hexenyl acetate. Catalyst loading required for different types of metathesis reactions. Examples of biologically

The activity of indenylidene derivatives in olefin metathesis catalysts

• Maria Voccia,
• Steven P. Nolan,
• Luigi Cavallo and
• Albert Poater

Beilstein J. Org. Chem. 2018, 14, 2956–2963, doi:10.3762/bjoc.14.275

• substitution, being 4.2 and 3.4 kcal/mol relatively more stable for systems 3 and 5, respectively, with respect to 1. This effect of reducing steric hindrance between the ylidene and the NHC ligands was examined previously, with the exchange of benzylidene by indenylidene [51]; and with larger NHC ligands [52

Synthesis of α-D-GalpN₃-(1-3)-D-GalpN₃: α- and 3-O-selectivity using 3,4-diol acceptors

• Emil Glibstrup and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2018, 14, 2805–2811, doi:10.3762/bjoc.14.258

• from the common 2-azidoglucose precursor 7, the 4,6-O-benzylidene group was removed with TsOH to give the 4,6-diol in 95% yield, followed by selective 6-O-protection using TBDPS-Cl and imidazole (IM) in 90% yield. The 4,6-O-benzylidene motif could also be regioselectively opened using triethylsilane

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• is a facile route to imines, which may be used for further functionalization. Our study began by examining a host of bases to convert N-chloramine 5 to benzylidene(methyl)amine (19) as a model reaction system (Table 4). To achieve a complete conversion, NEt3 was required in large excess (5 equiv

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• results outlined in Scheme 16 are consistent with early findings of Guthrie et al. exploring the Mitsunobu benzoylation of 4,6-O-benzylidene-D-allal [73]. Reactions with alcohols to yield alkyl glycosides In contrast to aryl ethers, the formation of alkyl ethers is not observed under Mitsunobu conditions

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• the central gluco-rhamno disaccharide the benzylidene protected glucosyl donor (Figure 2) was selected, because the induction of the 1,2-cis selectivity in benzylidene-protected substrates via torsional/electronic effects have already been recognized [28]. The galactosyl trichloroacetimidate donor 2

• was prepared following literature procedures [26]. On the other hand the D-glucosyl thioglycoside 8 was converted to the known benzylidene derivative 9 [29][30] according to our previously reported procedure. Benzylation of 9 under phase-transfer conditions led to 10 [31] in 49% yield (Scheme 1

• from NMR). We presume that this near exclusivity in α-selection may be due to the synergistic effect from the 4,6-O-benzylidene group, which is a good promoter for 1,2-cis glycosylation in galactose-based systems [38], as well as the steric crowding caused by the bulky 3-O-naphthylmethyl group at the β

Synthetic and semi-synthetic approaches to unprotected N-glycan oxazolines

• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 416–429, doi:10.3762/bjoc.14.30

• of the 3-branched arm. Subsequent removal (or regioselective reductive ring-opening) of the 4,6-benzylidene protecting group allowed a second glycosylation at position 6. Conversion of all OH-protecting groups to acetate and the phthalamide to acetamide was followed by oxazoline formation using TMSBr

• residues. Acid catalysed hydrolysis of the 4,6-benzylidene was followed by regioselective glycosylation of the primary 6-OH with a different pentasaccharide, this time comprised of five mannoses. Conversion of the azide to acetamide and removal of all benzyl groups by hydrogenolysis produced a completely

• ring opening of the less stable 5-ring benzylidene with DIBAL, led to a key disaccharide intermediate in which OH-3 of the mannose unit was unprotected and in which the 4- and 6-positions were protected as a benzylidene. Extension of this core disaccharide should be straightforward by traditional

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• -diazopyrazole derivative 158 with 4-substituted benzylidene-3-methyl-1H-pyrazol-5(4H)-one 159 in PEG-400. The reaction resulted in the synthesis of 6,7-dihydropyrazolo[1,5-a]pyrimidine derivatives 160 (Scheme 45). Selected compounds were studied for their interaction with calf thymus DNA using various

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• starting from azide 1 by first protecting the 3-OH group with an allyloxycarbonyl (Alloc) protecting group followed by regioselective reductive opening of the 4,6-O-benzylidene acetal using NaCNBH3 and HCl in diethyl ether, and successive phosphitylation of the liberated 4’-OH functionality with N,N

• reductive opening of benzylidene acetal using the borane−THF complex in the presence of Bu2BOTf. Regioselective TMSOTf-catalysed glycosylation of the diol 4 by the imidate donor 3 resulted in the formation of a single product, the β(1→6)-linked disaccharide 5. After the 2’-N-Fmoc group in 5 was removed with

• in AcOH which reductively cleaved the N-Troc group (Scheme 3). After N-acylation by (R)-3 acyloxyacyl fatty acid and hydrolytic cleavage of 4’,6’-O-benzylidene acetal group with 90% aqueous TFA, the liberated 6’-hydroxy group was regioselectively protected as TBDMS ether to furnish 20. 1H-Tetrazole

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• reactions was attributed to the formation of orthoester and oxazolidine side products due to the basic reaction conditions, which were needed to neutralize the acid formed during glycosylation and to avoid the cleavage of the acid-labile benzylidene protective group. The van der Marel group further applied