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

• imidazolium backbone and N substituents. The copper–NHC complexes tested are highly active for the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in an air atmosphere at room temperature in a CH3CN solution. Complex 4 is the most efficient catalyst among these polynuclear complexes in an air

• Inspired by the catalytic activity of Cu(I) species supported by NHC ligand in Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction under mild conditions, copper complexes 2–6 were investigated in the CuAAC reaction of azide and phenylacetylene. Firstly, we compared the catalytic activity of different

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• house is just as satisfying as that of a new molecule and often takes the same amount of time (left: Franck Boston copyright 123RF.com). Timeline of anion-binding macrocycles. Click chemistry’s copper-catalyzed azide–alkyne cycloaddition (CuAAC) forms 1,2,3-triazoles that stabilize anions by CH hydrogen

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• is the Cu(0)-catalysed azide–alkyne cycloaddition (CuAAC) that can be further enhanced by simultaneous US/MW irradiation [18]. The formation of triazole-substituted CDs has been investigated by US irradiation and products can be synthesized in 2–4 hours (Scheme 2) [19]. Scondo et al. have reported a

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• a cooper(I)-catalyzed azide–alkyne cycloaddition between the 2’-azido-β-CD 31 and the alkyne derivatives 22a,b to access the corresponding monosubstituted CD 32a,b [76]. Synthesis of 3-monosubstituted β-CD derivatives: As the facial position of the reactive groups might modify the catalytic

• partially-protected 2,6-dimethyl-β-CD (Scheme 7) [88]. Finally, CDs bearing an oxime (36 and 39a) or a hydroxamic acid (39b) group in position 3 were prepared as previously described via an azide–alkyne cycloaddition (Scheme 7) [76][80]. Synthesis of difunctionalized β-CD derivatives: As the hydrolytic

• disulfonylimidazole 42 to access a key intermediate easily converted to the corresponding di-2,3-mannoepoxido compound 43 (Scheme 8) [89]. The 3A,3B-diazido-3A,3B-dideoxy-bis(altro)-β-cyclodextrin 44 was then obtained by reaction of 43 with sodium azide and a copper(I)-catalyzed azide–alkyne cycloaddition finally

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

• Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, P. R. China 10.3762/bjoc.11.276 Abstract The Cu(I)-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles

• investigated and recognized as an epoch-making progress in organic synthesis and green chemistry [11][12][13][14][15]. After many years of research, it was proven that the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC reaction) could be performed under various conditions according to the need of click

• - and para-ethynylaniline, where both of the substrates worked well and the desired bistriazoles 34 could be obtained by a simple trituration and filtration procedure in good yield. The strain-promoted azide-alkyne cycloaddition (SPAAC) reaction could be well-performed without a Cu(І) catalyst. Such

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

• -deprotection with azide–alkyne cycloaddition, producing hindered triazoles in 6 hours. This tandem reaction was optimal with a copper(II) triflate and sodium ascorbate (NaAsc) as a mild reductant. The outcome that copper(II) triflate provides the highest yields for the one-pot deprotection/click reaction was

• unexpected as it is not known as a catalyst for azide–alkyne cycloaddition reactions [1][2]. Conclusion A tandem copper-catalyzed silyl deprotection/azide cycloaddition was developed for TIPS-protected tetrasubstituted propargylamines. These substrates are synthesized by a copper-catalyzed ketone–amine

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

• (Scheme 51). [3 + 2] Cycloaddition (1,3-dipolar cycloaddition/click reaction): In 2010, Raghunathan and co-workers [185] have synthesized a C2-symmetric triazolophane by a copper(I)-catalyzed azide-alkyne cycloaddition, involving a click reaction. The dipropargyl fluorenyl derivative 299 was prepared from

• ] have reported the synthesis of a glycotriazolophane 309 (carbohydrate–triazole–cyclophane hybrid) from a sugar amino acid via a copper-catalyzed azide-alkyne cycloaddition sequence. An aminosugar acid was identified as a useful building block to generate cyclophanes. Thus, the treatment of 304 with

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

• Carell et al. in 2007 [40]. The work of Aubé on AAC (azide–alkyne cycloaddition) chemistry also gives a good indication that equilibrating allylic azide stereoisomers can selectively participate in reactions [37][38][39][40][41][42][43][44][45]. In 2000, Aubé et al. proposed a mechanism for 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

• –alkyne cycloaddition (CuAAC) polymerization, were quarternized quantitatively with methyl iodide in sulfolane at 60 °C to obtain soluble oligomers. The conformation of the quarternized oligoAP in dilute DMSO-d6 solution was examined by pulse-field-gradient spin-echo NMR based on the touched bead model

• Shun Nakano Akihito Hashidzume Takahiro Sato Department of Macromolecular Science, Graduate School of Science, Osaka University, 1-1 Machikaneyama-cho, Toyonaka, Osaka 560-0043, Japan 10.3762/bjoc.11.116 Abstract 3-Azido-1-propyne oligomer (oligoAP) samples, prepared by copper(I)-catalyzed azide

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

• combines residue-specific incorporation of unnatural amino acids with chemical oxidative aldehyde formation at the N-terminus of a protein. Our approach relies on the selective introduction of two different functional moieties in a protein by mutually orthogonal copper-catalyzed azide–alkyne cycloaddition

• engineer multivalent glycoprotein conjugates, we have used the incorporation of non-canonical amino acids (NCAA) [13] by supplementation based incorporation (SPI) [14][15][16][17] in auxotroph expression systems followed by the chemoselective Cu-catalyzed azide–alkyne cycloaddition (CuAAC) to attach

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

• according to well-established protocols [65]. Consequently, we adopted the Sharpless–Fokin modification for the Huisgen azide–alkyne cycloaddition [66] to achieve the final immobilization of the modified imidazolidin-4-one onto the hyperbranched polymer and on the G1 dendron [65]. The progress of the

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

• 12) had marginal impact on the binding suggesting a saturation of binding site occupancy. For the structure with 6 units of maltose on each arm, a KD of 1 μM was measured which is 700-fold more potent (40-fold per sugar) than monovalent maltose. The advent of the copper-catalyzed azide–alkyne

• cycloaddition (CuAAC) [25][26] has naturally inspired the use of this powerful conjugation method to prepare glycan–DNA conjugates. Chevolot and co-workers used this method to conjugate glycans at the 3’-end of DNA [27]. The DNA synthesis was initiated with H-phosphonate that was converted to a phosphoramidate

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• interest of the pyrene scaffold lies in its rigidity, a property that may favourably impact inhibitory multivalent effects [9][11][16][19]. A convergent approach comprising the attachment of azide-armed iminosugars 4 [11][12] on polyalkyne “clickable” scaffolds 5 and 6 via Cu(I)-catalyzed azide–alkyne

• cycloaddition (CuAAC) was performed for achieving our synthetic goals (Figure 2) [56][57]. With the objective of increasing water solubility and chemical stability in biological medium, triyne 6b, an analogue of F-BODIPY-based scaffold 6a was prepared by replacing the fluoro groups on the boron center with

Synthesis and surface grafting of a β-cyclodextrin dimer facilitating cooperative inclusion of 2,6-ANS

• Lars W. Städe,
• Thorbjørn T. Nielsen,
• Laurent Duroux,
• Reinhard Wimmer,
• Kyoko Shimizu and
• Kim L. Larsen

Beilstein J. Org. Chem. 2015, 11, 514–523, doi:10.3762/bjoc.11.58

• −alkyne cycloaddition (CuAAC)) is very attractive [10][11]. CuAAC is known to be selective, proceed fast and produce a high yield under mild conditions. Further, the formed triazole is stable against oxidation, reduction and hydrolysis [10]. Concerning the design of β-CD dimers, it was recently

• to parent β-CD) for the inclusion of lipophilic molecules [5][9]. The extensive research on the topic has generated a vast number of different β-CD-dimer constructs and methods for the synthesis thereof. Of these methods, synthesis by click chemistry (and specifically the copper(I)-catalyzed azide

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

• methodology is more convenient to produce the complex polycyclic molecules in a simple way. Keywords: copper(II) acetate; decarboxylative CuAAC; dehydrogenative coupling; fused triazoles; one-pot synthesis; Introduction The copper-catalyzed Huisgen [3 + 2] cycloaddition (or copper-catalyzed azide–alkyne

• cycloaddition, CuAAC) between an organic azide and a terminal alkyne is a well-established strategy for the construction of 1,4-disubstituted 1,2,3-triazoles [1][2][3][4]. In a recent development, this decarboxylative coupling reaction was well documented for the generation of C–C bonds [5]. This method has

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

• )-catalyzed azide–alkyne cycloaddition (CuAAC) is often considered as the prototypical transformation [7][8][9]. Due to the mild conditions and the use of aqueous solvents it is an efficient tool for bioorthogonal chemistry even inside of living systems [10]. One application of this concept for functional

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• fact that it can be orthogonal to the azide–alkyne cycloaddition [22][26][27] which allows dual labeling of two different sugars within one experiment [19][21][23][24]. Among the dienophiles mentioned above, strained cyclopropenes have the highest reaction rates for DAinv reactions with tetrazines and

• by simultaneous DAinv reaction and strain-promoted azide–alkyne cycloaddition in a single step [24]. The potential of Ac4ManNCyoc (3) for labeling of sialoglycoconjugates was also recognized by others [30]. Sialic acids are prominently positioned at the outer end of membrane glycoproteins which makes

• biological events, 1 represents a promising probe for future glycomics studies. Of special interest is the fact that cyclopropene tags can be combined with azide–alkyne cycloaddition to achieve dual labeling of two different (sugar) moieties as was shown earlier [19][21][23][24][30]. Experimental General

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

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• have been widely studied in their scope and limitations [10][31]. In particular, the Huisgen cycloaddition reaction was first applied to a calixarene in 2000 by Santoyo-González [32]. Later on, Marra et al. [33] demonstrated that the copper-catalyzed azide–alkyne cycloaddition (CuAAC) [34][35] at room

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

• block AZO. TDS allows for the conjugation of sugar azide ligands via the copper-catalyzed azide–alkyne cycloaddition (CuAAC). The synthesis and coupling on solid support of TDS and EDS has been previously described [7][10]. AZO was synthesized via Mills coupling adapting literature protocols [20][21][22

The search for new amphiphiles: synthesis of a modular, high-throughput library

• George C. Feast,
• Thomas Lepitre,
• Xavier Mulet,
• Charlotte E. Conn,
• Oliver E. Hutt,
• G. Paul Savage and
• Calum J. Drummond

Beilstein J. Org. Chem. 2014, 10, 1578–1588, doi:10.3762/bjoc.10.163

• delivery. Many other fields have utilised the copper-catalysed azide–alkyne cycloaddition (CuAAC) ‘click’ reaction [16][17] to generate libraries of compounds, including enzyme inhibitors [18][19][20], catalysis ligands [21][22][23] and metal frameworks [24][25]. We have recently demonstrated that a

• organic amphiphilic compounds was synthesised consisting of glucose, galactose, lactose, xylose and mannose head groups and double and triple-chain hydrophobic tails. A modular, high-throughput approach was developed, whereby head and tail components were conjugated using the copper-catalysed azide–alkyne

• cycloaddition (CuAAC) reaction. The tails were synthesised from two core alkyne-tethered intermediates, which were subsequently functionalised with hydrocarbon chains varying in length and degree of unsaturation and branching, while the five sugar head groups were selected with ranging substitution patterns and

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• separating the anomeric and the core carbons, were synthesized using azide–alkyne cycloaddition (CuAAc). Compound 23 was prepared by an efficient convergent strategy. The sugar precursors consisted of either a 2-azidoethyl (3) or a prop-2-ynyl α-D-mannopyranoside (7) derivative. The solvodynamic diameters of

• above with 3-azido-1-propanamine to provide 6 in 87% yield. Azide–alkyne cycloaddition of 6 with prop-2-ynyl α-D-mannopyranoside 7 [35] gave 8 (79%) which was de-O-acetylated under Zemplén conditions (NaOMe, MeOH, 95%) to give 9. The syntheses of 9-mers 12, 17 and 21 are illustrated in Schemes 2–5 and

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• iminosugars 5 onto polyalkyne “clickable” scaffolds 2–4 by Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reactions [40][41] (Figure 1). N-alkyl derivatives of DNJ were logically chosen as the peripheral ligands because of the therapeutic relevance of these compounds [42]. In addition, most of the

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

• construction of a 1,4-disubstituted-1,2,3-triazole unit via a copper(I)-catalyzed modern version of the Huisgen-type azide–alkyne cycloaddition [6][7][8][9][10] has been considered to be a powerful ligation method for glycoconjugation [11][12][13][14][15][16]. In addition to the simplicity of this reaction and

Human dendritic cell activation induced by a permannosylated dendron containing an antigenic GM₃-lactone mimetic

• Renato Ribeiro-Viana,
• Elena Bonechi,
• Javier Rojo,
• Clara Ballerini,
• Giuseppina Comito,
• Barbara Richichi and
• Cristina Nativi

Beilstein J. Org. Chem. 2014, 10, 1317–1324, doi:10.3762/bjoc.10.133

• functionalized with an alkyne group by a Cu(I) azide–alkyne cycloaddition (CuAAC) reaction. Then, the mimetic 6 with a butyne group at the anomeric position, which is required for the conjugation to the glycodendron 7 (Scheme 1), was also prepared as already reported [33]. The synthesis of the tricyclic spiro