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

New metathesis catalyst bearing chromanyl moieties at the N-heterocyclic carbene ligand

• Agnieszka Hryniewicka,
• Szymon Suchodolski,
• Agnieszka Wojtkielewicz,
• Jacek W. Morzycki and
• Stanisław Witkowski

Beilstein J. Org. Chem. 2015, 11, 2795–2804, doi:10.3762/bjoc.11.300

• catalysts 1 and 2 [23]. The introduction of a nitro group into the 6-position of the chromene moiety in catalyst 8 led to a decrease in the stability of the complex [22]. The aforementioned modifications concerned the benzylidene moiety of the catalysts and affected the initiation rate of the metathesis

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• highest activity. In 2010, Nandurdikar et al. linked the two (or four) molecules of NO donor prodrugs together through the triazole spacers [22], which has potential application as NO-releasing materials. They first prepared the benzylidene-protected 2,2-di(azidomethyl)propane-1,3-diol containing the

Beyond catalyst deactivation: cross-metathesis involving olefins containing N-heteroaromatics

• Kevin Lafaye,
• Cyril Bosset,
• Lionel Nicolas,
• Amandine Guérinot and
• Janine Cossy

Beilstein J. Org. Chem. 2015, 11, 2223–2241, doi:10.3762/bjoc.11.241

• ligand present in 8 could prevent this side reaction. However, in the presence of diethyl diallylmalonate and n-butylamine, GII decomposed readily probably due to an increased instability of the less hindered methylidene 9 compared to benzylidene 8 (Scheme 3, reaction 3). Fogg et al. completed this study

• on the hindered benzylidene. With more sterically hindered amines b–d, the ruthenium complexes 11b–d, resulting from phosphine displacement, proved to be stable even after 24 h at 60 °C (Scheme 4). The half-life of methylidene 2 derived from GII in the presence of the amines were then evaluated using

• , several pathways are involved in the amine-induced catalyst decomposition depending on the nature of the amine and of the ruthenium complex. Non-bulky primary amines can attack directly benzylidene species and are responsible for the fast degradation of the catalyst. In the case of a phosphine-containing

Investigation on the reactivity of α-azidochalcones with carboxylic acids: Formation of α-amido-1,3-diketones and highly substituted 2-(trifluoromethyl)oxazoles

• Kandasamy Rajaguru,
• Arumugam Mariappan,
• Rajendran Suresh,
• Periasamy Manivannan and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2015, 11, 2021–2028, doi:10.3762/bjoc.11.219

• (Figure 2) [10][24]. In this article, we intend to demonstrate the reactivity of 2H-azirine A1 towards carboxylic acids [28]. α-Azidochalcones have been chosen to generate 2H-azirines via vinyl nitrene intermediates. α-Azidochalcones can be synthesized from the corresponding benzylidene acetophenones in

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