Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• ] cycloaddition of a ethynylstibane with organic azides in the presence of CuBr (5 mol %) under aerobic conditions. The reaction of 5-stibanotriazole with HCl, I2, and NOBF4 afforded 1-benzyl-4-phenyltriazole, 1-benzyl-5-iodo-4-phenyltriazole, and a pentavalent organoantimony compound, respectively. Keywords

• alkyne, an organic azide, and an H-phosphate in the presence of CuCl2 (10 mol %) and triethylamine (2 equiv) afforded the desired 1,2,3-triazolyl-5-phosphonates [23]. Fokin et al. carried out the reaction of ethynylbismuthane with organic azides using CuOTf (5 mol %) and isolated 5-bismuthano-1,2,3

• been no reports concerning the synthesis of 1,4,5-trisubstituted 5-stibano-1,2,3-triazoles. Herein, we report a novel CuAAC of a simple alkynylstibane, (phenylethynyl)di-p-tolylstibane, with organic azides to form fully substituted 5-organostibano-1,2,3-triazoles. Results and Discussion We initially

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• process involves the 1,3-dipolar cycloaddition of alkynes 182 with in situ generated nitrone 185 to afford isoxazolines 186 which rapidly rearrange to aziridinylphosphonates 183. An efficient method for the synthesis of 1,2,3-triazoles is the copper(I)-catalyzed Husigen cycloaddition of azides with

• alkynes. Based on this method, Li et al. have developed a copper(I)-catalyzed three-component reaction between alkynes 187, azides 188 and dialkyl phosphonates 189 to give 1,2,3-triazolyl-5-phosphonates 190 (Scheme 40) [78]. The desired products were obtained in 62–88% yield under optimized conditions

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• 2,1-benzisoxazole-3(1H)-ones is reported. The optimization and scope of this cyclization reaction is discussed. It is shown that an essential step of the ring closure of 2-azidobenzoic acids is the formation and photolysis of 2-azidobenzoate anions. Keywords: aryl azides; azepinones; 2,1

• nitro compounds [17][18][19][20][21], two other routes are available: the annulation of nitroso compounds [22][23] and the thermal [24], catalytic [25][26][27] or photochemical cyclization of aryl azides [28][29][30][31]. However, the presence of electron-withdrawing substituents in the 3-, 5- and 7

• -azepines 3 as products of the photolysis or thermolysis of aromatic azides [34][35]. The proposed mechanism for their formation was confirmed by identification of the reaction intermediates using low-temperature and time-resolved spectroscopy [36][37][38][39][40][41][42][43]. It is currently believed that

Bi- and trinuclear copper(I) complexes of 1,2,3-triazole-tethered NHC ligands: synthesis, structure, and catalytic properties

• Shaojin Gu,
• Jiehao Du,
• Jingjing Huang,
• Huan Xia,
• Ling Yang,
• Weilin Xu and
• Chunxin Lu

Beilstein J. Org. Chem. 2016, 12, 863–873, doi:10.3762/bjoc.12.85

• yield (Table 1, entry 4). However, only a moderate yield was obtained when a CH3CN/H2O solvent mixture was used (Table 1, entry 6). Thus, CH3CN was selected as the optimal solvent. Having optimized the reaction conditions, we extended the CuAAC reaction to other azides and alkynes at room temperature in

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• blocks in synthetic organic chemistry. Recently, they have attracted also strong interest for applications in materials science and chemical biology [1]. One of the most important transformations of alkynes is the copper-catalyzed [3 + 2] cycloaddition with azides, which can be performed under mild

• modified reaction conditions (10 mol % AuCl(SMe2), three equivalents TIPS-EBX (1a) and 2 mol % trifluoroacetic acid as co-catalyst) [39]. They also demonstrated that the obtained silylalkyne products can be easily deprotected with fluoride sources to allow bioconjugation via cycloaddition with azides

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

• coupling; Introduction Since its discovery by Huigsen and co-workers fifty years ago [1][2][3][4], the Huisgen cycloaddition of azides to alkynes has gained much attention due to its potential to yield a wide variety of triazoles with structurally diverse and functionalized groups, especially with respect

• from a double CuAAC reaction between various sources of 1,3-butadiynes with the substituted azides. In general, two different methods have been developed for the construction of the 4,4'-bitriazoles: (1) The one-pot double CuAAC reaction of 1,3-butadiyne with azides. (2) Two successive CuAAC reactions

• with different or same azides that require the deprotection of the second reactive site to liberate another alkyne moiety. In 2007, Monkowius et al. reported that the 4,4'-bitriazoles 3 could be synthesized by the two-fold click reaction between 1,3-butadiyne and substituted organic azides [17], and

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides

• Madhuri Vangala and
• Ganesh P. Shinde

Beilstein J. Org. Chem. 2015, 11, 2289–2296, doi:10.3762/bjoc.11.249

• glycosyl azides via intramolecular condensation with a vicinal ester group in the presence of triphenylphosphine [27] or from the reaction of D-glucals with N-iodosuccinimide and amides [28][29]. Alternatively, 5 can be derived by a Ritter-like [30][31] transformation, involving trapping of the

Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

• Redouane Beniazza,
• Natalia Bayo,
• Florian Molton,
• Carole Duboc,
• Stéphane Massip,
• Nathan McClenaghan,
• Dominique Lastécouères and
• Jean-Marc Vincent

Beilstein J. Org. Chem. 2015, 11, 1950–1959, doi:10.3762/bjoc.11.211

• photoreduced in water when alkynes were present in solution. The catalytic activity of 1 for click reactions involving a range of water-soluble alkynes and azides, in particular saccharides, was tested under various illumination conditions. Complex 1 was found to exhibit a photolatent character, the

• when exposed to TLC lamp. Having established the most efficient illumination conditions, reactions were conducted on a range of water-soluble alkynes and azides by irradiating the NMR tubes with the TLC lamp for 1 h and then leaving it under ambient light. As seen in Scheme 4, a variety of triazoles 9

• spectroscopy, that the alkynes can serve as effective and practical electron source to allow the reduction in a light-dependent process photosensitized by the benzophenone. Complex 1 proved to be an effective photolatent catalyst for reactions conducted in water involving water-soluble alkynes and azides

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• -caboxylates we obtained by using our method (Table 1) compares favorably with three recently published methods where arylmethyl azides [22], arylallyl azides [23] and o-nitrobenzaldehydes [24] were used as starting materials. The mechanism of heterocyclic ring expansions has briefly been studied for thermal

Reaction of allene esters with Selectfluor/TMSX (X = I, Br, Cl) and Selectfluor/NH₄SCN: Competing oxidative/electrophilic dihalogenation and nucleophilic/conjugate addition

• A. Srinivas Reddy and
• Kenneth K. Laali

Beilstein J. Org. Chem. 2015, 11, 1641–1648, doi:10.3762/bjoc.11.180

• presence of phosphane catalysts an umpolung addition takes place, whereby the nucleophilic addition occurs inversely at the beta-gamma double bond [22][23]. Vinyl azides have been prepared by hydroazidation of allenyl esters through a Michael-type addition with high regio- and stereoselectivity [24

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• second portion of the sequence in Scheme 1: a tandem deprotection–cycloaddition of tetrasubstituted TIPS-protected propargylamines 4 that would allow them to react in situ with various azides 5 to give hindered triazoles 6. As a copper(I) catalyst is required for azide–alkyne cycloaddition, the

• . Alternate organic azides were synthesized according to known methods [39][40][41]. 4-Methylbenzyl azide forms triazole 6g in a comparable yield to 6a, but electron-poor 4-(trifluoromethyl)benzyl azide forms triazole 6h in lower yield. Aryl and alkyl azides display parallel reactivity in the formation of

• /cycloaddition. Tetrasubstituted silylpropargylamines form hindered triazole products. Assorted azides for formation of alpha-tetrasubstituted triazoles. Supporting Information The Supporting Information features experimental details, compound characterization, and copies of 1H and 13C NMR spectra of triazoles

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• 9H-fluorene (298) and propargyl bromide, which on further treatment with 1,4-diazidobutane (300) and xylyl azides 302a–c in the presence of CuSO4·5H2O and sodium ascorbate in THF/water (1:1) gave the corresponding macrocycles (301, 42%) and (303a–c, 60–70% yield, Scheme 52). Murphy and Leyden [186

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• inventory of the reactive intermediate reduced the safety concerns associated with the use of the azide. The choice of flow when handling hazardous materials like azides is a very frequently encountered driver and several publications detailing the associated benefits have emerged over the years [88][89][90

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