Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• intermolecular ring-expansion reaction of hydroxy azides with cyclic ketones. This involves the Lewis acid-promoted formation of an N-diazonium intermediate, which undergoes rearrangement to give an iminium ether intermediate that can be hydrolyzed by a base [8][41]. Along these lines we have proposed the

Quarternization of 3-azido-1-propyne oligomers obtained by copper(I)-catalyzed azide–alkyne cycloaddition polymerization

• Shun Nakano,
• Akihito Hashidzume and
• Takahiro Sato

Beilstein J. Org. Chem. 2015, 11, 1037–1042, doi:10.3762/bjoc.11.116

• . Keywords: 3-azido-1-propyne oligomer; CuAAC polymerization; hydrodynamic radius; methyl iodide; pulse-field-gradient spin-echo NMR; quarternization; Introduction The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) efficiently yields 1,4-disubstituted-1,2,3-triazole from rather stable azides and

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• solution [50], was applied in all coupling reactions and conversions were again checked by MALDI–MS, gel electrophoresis and Western Blot (Figure 1B,C, lane 4). As evidenced by MS-analysis, we could observe that both proteins Ser-TTL[Aha] (nine azides) and AhaSer-TTL[Aha] (ten azides) reacted with

• , different linker lengths should be probed to allow better binding of multiple carbohydrate units of one protein scaffold with multiple binding sites of one lectin molecule. Conclusion In conclusion, we succeeded in the incorporation of two unnatural functional groups, namely azides and aldehydes, into a

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• a one-step ring opening anionic polymerization (ROAP) [49]. The controlled mesylation on hPG 1 yielded 2a–c (95%, 57% and 30% of functionalization, respectively (for details see Supporting Information File 1)), which were converted to the corresponding azides 3a–c [63][64]. Azide 6 was prepared

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• diverse glycans could be iteratively introduced on amino acid linkers. Inspired by Shoda’s activation [40] which provides facile access to complex glycosyl azides from native carbohydrates, we subsequently applied reiterative CuAAC conjugation of glycans on propargyl glycine residues within a peptide [41

• selectivity of the lectins. More recently, we reported a combinatorial synthesis of a more diverse library of PNA-encoded glycoconjugates (10,000 members) [41]. The combinatorial synthesis was performed using two sequential CuAAC conjugations with 33 diverse glycosyl azides separated by 3 different peptide

The preparation of new functionalized [2.2]paracyclophane derivatives with N-containing functional groups

• Henning Hopf,
• Swaminathan Vijay Narayanan and
• Peter G. Jones

Beilstein J. Org. Chem. 2015, 11, 437–445, doi:10.3762/bjoc.11.50

• analysis. Keywords: azides; crownophanes; cyclophanes; isocyanates; stereochemistry; X-ray analysis; Introduction Although hundreds of mono- und disubstituted derivatives of [2.2]paracyclophane [3][4] have been described since its initial preparation [5], relatively little is known about more highly

Functionalized branched EDOT-terthiophene copolymer films by electropolymerization and post-polymerization “click”-reactions

• Miriam Goll,
• Adrian Ruff,
• Erna Muks,
• Felix Goerigk,
• Beatrice Omiecienski,
• Ines Ruff,
• Rafael C. González-Cano,
• Juan T. Lopez Navarrete,
• M. Carmen Ruiz Delgado and
• Sabine Ludwigs

Beilstein J. Org. Chem. 2015, 11, 335–347, doi:10.3762/bjoc.11.39

• pyrrole was conducted [30]. Post-polymerization processes on the other hand have to provide high yields and mild reaction conditions to keep the formed polymer backbone intact and to reach a considerable degree of conversion of functional groups. The Cu(I)-mediated 1,3-dipolar cycloaddition between azides

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• azides, 11 and 12, epimeric at C-5, in a relative ratio 2:1 with a global yield of 85%. Two azides were separated by flash chromatography (CH2Cl2/MeOH 98:2 as eluent). Compound 12 originates from 11: its formation can be rationalized by considering that the acidic medium of the reaction, linked to the

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• defined a 1,2,3-triazole containing linkage between two piperidine rings as the flexible joint F, which should be easily accessible by copper-catalyzed cycloaddition between an azide G and a terminal alkyne H (CuAAC, “Click” reaction) [16]. Primary alcohols I serve as “protected” azides accessible by

• with arbitrary functionalities in the terminal positions we used trimethylsilyl alkynes and primary alcohols as protected alkynes and azides, respectively. Pursuing this approach we prepared a variety of ARs with different groups in terminal positions. The AR 32a, bearing pyrene moieties turned out to

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• /bjoc.10.325 Abstract The mono-6-deoxy-6-azides of 2,6-di-O-methyl-β-cyclodextrin (DIMEB) and randomly methylated-β-cyclodextrin (RAMEB) were conjugated to propargylated hydroxyethyl starch (HES) by Cu+-catalysed [2 + 3] cycloaddition. The resulting water soluble polymers showed lower critical solution

• like chitosane [29], alginate [24] and dextrane [28] is advantageous for the design of drug delivery systems because of the low toxicities and biodegradabilities of those polymers. Among the various coupling reactions, the [2 + 3] cycloaddition of alkynes and azides, the so-called Huisgen reaction [30

• propargyl ether leading to a highly water soluble polymer 3 with DSHES(propargyl) = 0.55. Coupling of the CD azides 1a and 1b to the propargylated HES was performed by Cu+-catalyzed [2 + 3] cycloaddition, the so-called click reaction, leading to the corresponding triazol groups (Scheme 3). The standard

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• organic azides. This kind of decarboxylative CuAAC reaction has not been further investigated. Transition metal-mediated C–H bond activation has become a hot topic in recent years [7][8][9][10][11]. Formally, it requires insertion of a transition metal (usually Pd, Ru, Rh or Ir) across a strong C–H bond

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• bioactive metabolites and selective labeling of proteins and other biomacromolecules. A common structural motif for such probes consists of a reporter that can be attached by copper(I)-catalyzed 1,2,3-triazole formation between terminal alkynes and azides to a reactive headgroup. Here we introduce the

• compatibility with widely applicable CuAAC approaches, that are, for instance, used in the field of ABPP where fluorescent reporter azides act as part of protein probes. To avoid the need for expensive detection systems for in-gel fluorescence we adjusted the excitation and emission wavelengths of the reporter

• with the four azides BPT (1), DNS (8), NBD (9) and BNS (6). After one hour of incubation with lysine the respective reporter, the ligand 1-(1-benzyltriazol-4-yl)-N,N-bis[(1-benzyltriazol-4-yl)methyl]methanamine (TBTA), sodium ascorbate and a copper sulfate solution were added and incubated for another

Indium-mediated allylation in carbohydrate synthesis: A short and efficient approach towards higher 2-acetamido-2-deoxy sugars

• Christopher Albler,
• Ralph Hollaus,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2014, 10, 2230–2234, doi:10.3762/bjoc.10.231

• . Deacetylation in a methanolic HCl solution proved to be most efficient and the subsequent ozonolysis generated sugar azides 6a–c (Scheme 2). It turned out to be essential to perform the acidic acetate cleavage of compounds 5a–c under strictly dry conditions, since even small amounts of water promoted an

Organophosphorus chemistry

• Paul R. Hanson

Beilstein J. Org. Chem. 2014, 10, 2087–2088, doi:10.3762/bjoc.10.217

• phosphanylidenecarbenes and phosphoryl azides, and bisphosphonate ethers as promising inhibitors of geranylgeranyl diphosphate synthase (GGDPS). The articles and reviews capture the emerging potential of organophosphorus compounds and exciting opportunities in the field, and hopefully, will inspire and motivate

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• -triazine (2) as a key precursor [37]. The glycosyl units were incorporated via Cu(I)-catalyzed Huisgen cycloaddition with protected or unprotected glycosyl azides. We first investigated the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) of acetyl protected β-D-galactopyranosyl azide 3 [38], to tris

• unprotected azidosugars were obtained by straightforward deprotection of the corresponding acetyl-protected azides [38]. The trivalent glycoclusters decorated with D-galactose, 1, D-glucose, 13, and L-fucose, 14, epitopes were thus obtained directly in 53%, 50%, and 44% yields, respectively, after reversed

• 34% yield. A second [3 + 2] cycloaddition with a different glycoside, such as D-glycopyranosyl azide 8, under the same conditions, provided for example the mixed Gal2-Glc triazine cluster 17 (Scheme 2). The efficient conjugation of unprotected glycosyl azides to trithiotriazine 2 thus provides

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• active complexes allows the identification of structural features essential for biological activity. Keywords: azides; click-chemistry; cycloadditions; cytotoxicity; titanocenes; Introduction Group 4 metallocenes and derivatives of Cp2TiCl2, in particular, continue to be in the focus of contemporary

• A–D shown in Figure 2 were used as amino-substituted azides. They are readily obtained from the corresponding diazides through a Staudinger reaction (see Supporting Information File 1 for details) [45][46]. As for the carboxylates the different tether lengths and substitution patterns of the arene

• allow to study the effect of substitution on the activity of the complexes. The ether tether in B serves as a model for PEG. The titanocene carboxylates 1–3 were transformed into the corresponding acid chlorides and then reacted with amino azides A–D in the presence of NaH without purification of the

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• steps, the oligomeric backbone was formed on the solid support. In the next step, the sugar ligands were introduced to the oligomeric backbone via CuAAC. To this end, two sugar azides (2-azidoethyl galactoside and 2-azidoethyl mannoside) were previously synthesized following literature protocols [26]. 8

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• protocol and the results are summarized in Table 2. Different azides 1a–j with electron-donating groups (Table 2, entries 2–8, 12–17, 20–23), electron-withdrawing groups (Table 2, entries 9, 10, 18 and 19), two different 4-(prop-2-yn-1-yloxy)benzaldehydes 2a,b, and two different 1,2-diaminobenzenes 3a,b

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• onto polymers from a single monomer via convenient ‘click’ chemistry with organic azides. The incorporation of various pendant functional groups could effectively tailor the physicochemical properties of polylactide. The reported synthesis of 1 started from propargyl bromide and ethyl glyoxylate

• groups onto polymers via convenient ‘click’ reaction with organic azido molecules without PLA backbone degradation [17]. ‘Click’ chemistry [20], which is copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and alkynes, has been developed and utilized in recent years as a powerful synthetic strategy

• family of water-soluble and temperature responsive biodegradable PLA material with tunable lower critical solution temperature (LCST) in a range from 25 to 65 °C was obtained after ‘click’ grafting with a mixture of alkyl and PEG azides. Starting from the same precursor 1 [18], Yu and coworkers have

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• both alcohols showed a diastereomeric purity of >99% by 1H NMR. Mitsunobu reaction on the secondary alcohols using DEAD or DIAD did not provide the desired azides [42][43] nor did a one-pot Appel reaction/nucleophilic substitution/Staudinger reaction protocol involving a double inversion of

Design and synthesis of multivalent neoglycoconjugates by click conjugations

• Feiqing Ding,
• Li Ji,
• Ronny William,
• Hua Chai and
• Xue-Wei Liu

Beilstein J. Org. Chem. 2014, 10, 1325–1332, doi:10.3762/bjoc.10.134

• -dideoxysugars and azides with various substituent groups (R2) were screened and the summarized results are shown in Table 3. Overall, the yields obtained were from good to excellent while preserving the anomeric selectivity and regioselectivity. In general, the analogous reaction of a set of azides with

• conjugations to microwave irradiation. All the reactions were completed in considerably shorter reaction times of less than 30 min for the Huisgen cycloaddition of alkenes and azides catalyzed by copper sulfate and sodium ascorbate, affording the corresponding products in good to excellent yields in each case

• has been established that the construction of well-defined multivalent, anomerically pure 3-amino-2,3-dideoxyneoglycoconjugate architectures was successfully achieved by using cycloaddition reactions of alkynes and azides. It is expected that this strategy will find extensive applications in

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• , polymers, supramolecules and other smart materials [2][3][4][5][6][7][8]. In order to explore more applications of triptycenes, there is a need to design newer derivatives of triptycene having specific functional groups. It is well established that aromatic azides are an important class of compounds having

• various interesting applications in organic chemistry [9][10][11] as well as material science [12][13][14][15] and drug discovery [16][17][18]. Organic azides in general are popular in recent times because of their use as synthons in Cu(I)-catalyzed “click chemistry” [19]. It is also well known that

• : 3.58 × 104 M−1 cm−1). The absorption spectra of 3 and 4 have a broad shoulder at around 300 nm, and this is due to n–π* transitions in the azides. Triptycene based tricarboxylic acids 5 and 6 exhibited two broad absorption bands centered at 280 nm (ε: 1.94 × 104 M−1 cm−1 for 5 and 3.06 × 104 M−1 cm−1

Synthesis of chiral N-phosphoryl aziridines through enantioselective aziridination of alkenes with phosphoryl azide via Co(II)-based metalloradical catalysis

• Jingran Tao,
• Li-Mei Jin and
• X. Peter Zhang

Beilstein J. Org. Chem. 2014, 10, 1282–1289, doi:10.3762/bjoc.10.129

• chiral catalysts, such as Mn, Fe, Cu, Rh, Ru and Co complexes, have been demonstrated as effective catalysts in asymmetric olefin aziridination with various nitrene sources, including the widely used iminoiodanes and their in situ variants, chloramine-T, bromamine-T, tosyloxycarbamates and organic azides

• [9][10][11][12][13][14][15]. Among them, the organic azides have recently emerged as attractive alternative nitrene sources for metal-catalyzed aziridination because of many advantages such as ease of preparation, structural diversity, and N2 gas as the only byproduct [13][14][15]. While sulfonyl and

• aryl azides have been effectively employed for metal-catalyzed asymmetric aziridination [16][17][18][19], the catalytic system based on other types of azides, such as phosphoryl azides, remains underdeveloped. Phosphoryl azides, a family of common organic azides that can be directly synthesized from

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

• alcohols with various sulfonyl azides is found to undergo a concomitant intramolecular nucleophile attack to generate 1,2-dihydro-2-iminoquinolines after aromatization (via elimination of acetyl and hydroxy groups) and tautomerization. The reaction produces 4-substituted and 3,4-unsubstituted title

• compounds in moderate to good yields under mild reaction conditions. Keywords: alkyne; azide; cycloaddition; cyclization; quinoline; Introduction The synthesis of N-sulfonylketenimines via CuAAC (copper-catalyzed azide–alkyne cycloaddition) between terminal alkynes and sulfonyl azides has staged for a

• herein report a synthesis of 1,2-dihydro-2-iminoquinolines (tauromerized form of 2-sulfonylaminoquinolines) from 1-(o-acetamidophenyl)propargyl alcohols via copper-catalyzed ketenimine formation with various sulfonyl azides. 2-Aminoquinolines and their derivatives have been found to be important

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• ) satisfactory aqueous solubility and independent binding capacity of the cavities. Keywords: calculations; conformations; cyclodextrin; dimer; inclusion; PM3; Staudinger ligation; Introduction The Staudinger reaction [1] is a classical method for the preparation of amines from phosphines and azides [2][3

• preference for the self-inclusion configurations. The method can be clearly utilized for dimer formation using other cyclodextrin azides, provided that there is a long enough spacer connecting the azido group with the CD macrocycle. 1H NMR chemical shift change (Δδ) of CD cavity Η3 signal of compounds