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

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• used for tethering with a glycosyl donor using a similar tethering concept to afford compound 43. The second glycosylation reaction is conducted in the presence of iodine in methanol. These conditions allow to cleave benzylidene groups concomitantly with the activation of the leaving group. As a result

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• 83. The latter underwent a Michael cyclization reaction to afford 84. Finally, dehydratation of 84 gave the spiro bis-indane product 85 (Scheme 27). A new method to synthesize 2-benzylidene-1-indanone derivatives 88a–d has been proposed in 2014 by Álvarez-Toledano et al. [52]. These derivatives were

• tirelessly exploring for better anticancer pharmaceuticals. Negi et al. have joined these efforts and proposed a synthesis of 2-benzylidene-1-indanones, which exhibited a strong cytotoxicity against four human cancer cell lines: breast (MCF-7), colon (HCT), leukemia (THP-1) and lung (A549) with IC50 values

• -Benzylidene-1-indanones 126a–o were obtained by a Knoevenagel condensation of 1-indanone 125 with various aromatic aldehydes. Hydrogenolysis of 2-benzylidene-1-indanone 126b using Pd/C allowed to obtain 2-benzyl substituted 1-indanone 127 (Scheme 40). 2-Bromo-6-methoxy-3-phenyl-1-indanone 130, as an

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• blocks 10 and 7 [27] in a dichloromethane–ether (enables alpha selectivity) mixture in 56% yield (Scheme 4). Removal of the silyl ether and benzylidene groups of 19 yielded triol 20 before benzylation afforded disaccharide thioglycoside building block 21. Activation of disaccharide 21 resulted in the

• glycosylation of mannosazide acceptor 18 (Scheme 3) to form the corresponding α-linked trisaccharide, which, subsequent to removal of the 4,6-benzylidene group under acidic conditions, provided diol 22 that was in turn converted into reducing-end trisaccharide 3 by selective placement of a TBS ether [28] on the

• subsequently converted to the fucosyl trichloroacetimidate building block 8 (Scheme 5). Galactosyl thioglycoside 9 was prepared from D-galactose following published procedures [32]. Reductive opening of the benzylidene acetal of known galactosyl thioglycoside 29 [33] with triethylsilane [34] in TFA/CH2Cl2

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

• thioglucoside 45 was found to be much less reactive than 20 and only couples to armed donor/acceptors in low yield (Figure 4) [24]. This is analogous to the effect of the very similar benzylidene group, which is deactivating the donor partially due to locking the structure in an unreactive conformation and due

• 4,6-O-benzylidene-protected thioglucoside donor, which has been shown by Crich to be α-selective, the α-selectivity increased even more when a 2-O-benzyl was exchanged with 2-O-TBS or 2-O-TIPS [54]. The authors suggested that the silyl group had an inductive effect that favored α-formation. The 4,6-O

• and with N-phenyltrifluoroacetimidate as the leaving group [57][58]. A somewhat similar influence has been observed with the much less steric demanding 4,6-O-benzylidene protective group [59]. A related stereoselectivity is induced by the DTBS group in arabinofuranosylations. Boons and collaborators

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• aniline at room temperature under solvent-free conditions (Scheme 1). Then, the reaction of N-benzylidene(butyl)amine (1a) with four different dialkyl phosphites and diphenylphosphine oxide was investigated under MW-assisted solvent-free conditions searching for the optimum temperature and reaction time

• aminophosphine oxide 2e was obtained in a yield of 89% (Table 1, entry 11). Next N-benzylidene(cyclohexyl)amine (1b) was tried in the aza-Pudovik reaction (Table 2). Its reaction with 1.2 equivalents of DMP at 80 °C for 30 min led to aminophosphonate 4a at a conversion of 89% (Table 2, entry 1). Even at 100 °C

• reaction of N-benzylidene(cyclohexyl)amine (1b) with DBnP at 100 °C afforded the target compound 4d in a conversion of 100% that could be isolated in a yield of only 68% (Table 2, entry 7). The phosphinoylation of imine 1b was carried out at 100 °C for 10 min. The yield of ((cyclohexylamino)(phenyl)methyl

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• and 4 in selenofucoside 1. The introduction of a 3,4-O-benzylidene protecting group using benzaldehyde dimethyl acetal under standard conditions was ineffective and degradation was observed by TLC. However, the formation of the 3,4-O-benzylidene acetal could be achieved through in situ evaporation of

• the reaction byproduct methanol as previously reported by Evans [35] for methyl O-glucosides. Using the same conditions, 4,6-benzylidene protection was successfully introduced into a phenylseleno glucoside by Fairbanks et al. [36] without observed degradation at ambient pressure. The increased

• ). Due to the unsuccessful removal of the benzylidene group in 6, unprotected selenofucoside 1 was directly methylated with MeI (Scheme 1). However, only a slow conversion was observed and various products were detected on TLC lacking predominant formation of only one regioisomer. To overcome the

Catalytic Wittig and aza-Wittig reactions

• Zhiqi Lao and
• Patrick H. Toy

Beilstein J. Org. Chem. 2016, 12, 2577–2587, doi:10.3762/bjoc.12.253

• as the catalyst for phosphine oxide reduction. Using similar conditions the corresponding reactions of carboxylic acids 74 with aromatic acid chlorides 72 produced 4-benzylidene-2-aryloxazol-5(4H)-ones 75. Lastly, the research group of Piet Herdewijn extended this general concept and reported

An effective one-pot access to polynuclear dispiroheterocyclic structures comprising pyrrolidinyloxindole and imidazothiazolotriazine moieties via a 1,3-dipolar cycloaddition strategy

• Alexei N. Izmest’ev,
• Galina A. Gazieva,
• Natalya V. Sigay,
• Sergei A. Serkov,
• Valentina A. Karnoukhova,
• Vadim V. Kachala,
• Alexander S. Shashkov,
• Igor E. Zanin,
• Angelina N. Kravchenko and
• Nina N. Makhova

Beilstein J. Org. Chem. 2016, 12, 2240–2249, doi:10.3762/bjoc.12.216

• generated from isatins and sarcosine to benzylidene derivatives of the same imidazothiazolotriazine will proceed from the less sterically hindered side [41] (anti attack). Herein, we report a regio- and diastereoselective one-pot method for the synthesis of a novel class of polynuclear dispiroheterocyclic

• cycloaddition with compound 1a (Scheme 3, Figure 2). It was found that apart from model substrate 3a, N-alkyl- (3b,c), N-allyl- (3d) and N-methyl-5-bromoisatins (3e) reacted with sarcosine and dipolarophile 1a to afford the desired products 4a–e in 54–78% yields. Next, the nitrobenzylidene and benzylidene

• for the generation of the azomethine ylide as well as for nitrobenzylidene derivative 1b as dipolarophile. To further extend the substrate scope of this reaction, we used benzylidene derivatives of other imidazothiazolotriazines 1d–f without substituents at the bridge carbon atoms C(3a) and C(9a). The

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• with a similar substitution pattern. In the myxobacterial metabolites an E-configuration was found at the benzylidene unit, whereas the nostoclides and cyanobacterin have a Z-configuration. Only the anhydro form of cyanobacterin was found to isomerize from the Z- to the E-configured isomer in organic

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• ] of 14 followed by azidolysis [41] furnished 15. 2-Azido-3,4-epoxide 18 was prepared from readily available [42] 2,3-isopropylidene-D-mannosan (16) in five steps (Scheme 2). Tosylation of 16 [43], followed by hydrolysis of the benzylidene acetal [44] and oxirane ring closure [45] at C-4 delivered 1,6

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• the reaction conditions the yields of products 231 were 71–91%. Barbas and co-workers reported the synthesis of carbazole spiro-oxindole derivatives, in a Diels–Alder reaction in very short reaction time (10 min). The reagents were the substituted indoles 233, benzylidene oxindolinones 234 and the

Simple activation by acid of latent Ru-NHC-based metathesis initiators bearing 8-quinolinolate co-ligands

• Julia Wappel,
• Roland C. Fischer,
• Luigi Cavallo,
• Christian Slugovc and
• Albert Poater

Beilstein J. Org. Chem. 2016, 12, 154–165, doi:10.3762/bjoc.12.17

• ). The minor isomer 2a (28% yield) was identified as the OC-6-14 diastereomer featuring the two oxygen atoms in trans disposition (and the nitrogen atom trans to the benzylidene ligand). The major isomer 2b (57% yield) is the OC-6-32 diastereomer bearing the two oxygen ligands in cis disposition (and one

• oxygen atom is coordinated trans to the benzylidene ligand). Elemental analysis confirmed the proposed stoichiometry of the complexes. Characteristic 1H NMR signals comprise the protons in position 2 of the quinolinolate moieties. These protons resonate in the low-field (between 9.00 ppm in 2b and 7.90

• readily evident from the benzylidene proton chemical shifts of 19.10 and 18.24 ppm, which are distinctly low-field shifted in comparison to the same signal in HovII (16.56 ppm). From single crystal X-ray structure analyses of 2a and 2b it became evident that, in general, bond lengths and angles are very

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• backbone is a much better approach than the previously used ones (e.g., via phosphine or benzylidene ligands). An early example of a non-covalent attachment is complex 4, an activated catalyst deposited on glass polymer Raschig rings, which was tested in various metathesis reactions carried out in batch