Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• of 1,2,3-triazoles can connect several components in one molecule [25][26]. CuAAC belongs to the class of chemical processes called “click-chemistry” and it is also a biorthogonal reaction because functional groups of natural biopolymers are not affected and do not participate in chemical

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

• University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan 10.3762/bjoc.12.123 Abstract Trisubstituted 5-stibano-1H-1,2,3-triazoles were synthesized in moderate to excellent yields by the Cu-catalyzed [3 + 2

• : cycloaddition; copper catalyst; ethynylstibane; organic azide; 1,2,3-triazole; Introduction The 1,3-dipolar azide–alkyne cycloaddition (AAC) has been effective for the synthesis of a wide variety of 1,2,3-triazoles [1]. However, this reaction has some limitations such as the requirement of high temperature and

• -disubstituted 1,2,3-triazoles. Since then, the CuAAC has been widely applied in organic synthesis [4][5][6][7][8][9][10][11][12], molecular biology [13][14][15][16][17], and materials science [18][19][20]. There are many reports of CuAACs by using terminal alkynes (including metal acetylides) [4][5][6][7][8][9

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

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

• , the easy synthesis and versatile coordination ability of 1,2,3-triazoles have led to an explosion of interest in coordination chemistry [21] and homogeneous catalysis [22][23][24][25][26]. Although a number of metal complexes containing 1,4-disubstituted-1,2,3-triazole ligands were well studied

• , reports concerning their preparation and use of 1,4-disubstituted-1,2,3-triazoles bearing NHC ligands are rare [22][23]. Elsevier et al. [23] reported several of palladium(II) complexes containing a heterobidentate N-heterocyclic carbene-triazolyl ligand. These palladium(II) complexes are active

• via reacting methyl propiolate with (azidomethyl)benzene. This promising catalytic behavior of complex 4 prompted us to extend our studies toward a one-pot synthesis of 1,2,3-triazoles from alkyl halides, sodium azide, and alkynes. The three-component version has already been successfully performed

Creating molecular macrocycles for anion recognition

• Amar H. Flood

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

• activity surrounding 1,2,3-triazoles made using click chemistry; and the same triazoles are responsible for anion capture. Mistakes made and lessons learnt in anion recognition provide deeper understanding that, together with theory, now provides for computer-aided receptor design. The lessons are acted

• microscopy (STM) imaging. Their shape persistence makes them ideal for the study of structure–property relationships to enable deep understanding of anion recognition phenomena. The identification of 1,2,3-triazoles as linkers, ligands and building blocks. The synthetic creation of macrocycles sets the scene

• it was an old reaction, the Huisgen cycloaddition, made good (regioselective) with the aid of copper catalysis. Taking that idea on face value, I reasoned that click chemistry was a new and extremely effective way to make 1,2,3-triazoles. It is not often that either new or newly refined reactions

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

• . Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC) for such transformations. In

• 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

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

• 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

• flasks (Scheme 5). The hydrogenated triazoles 18 and 19 were obtained in 86% (0.450 g) and 82% (0.644 g) isolated yields, respectively, showing that the procedure is practical for laboratory-scale applications. Conclusion The copper(II) precatalyst 1 incorporating a benzophenone chromophore is easily

• . Proposed mechanism for the photoreduction process. Structures, conversions and isolated yields for triazoles 9–17 conducted in D2O in NMR tubes. Preparative scale synthesis of 18 and 19. Supporting Information Supporting Information File 494: Experimental and analytical data. Supporting Information File

Synthesis, antimicrobial and cytotoxicity evaluation of new cholesterol congeners

• Mohamed Ramadan El Sayed Aly,
• Hosam Ali Saad and
• Shams Hashim Abdel-Hafez

Beilstein J. Org. Chem. 2015, 11, 1922–1932, doi:10.3762/bjoc.11.208

• , hydroxyalkyl-1,2,3-triazoles were reported as valuable pharmacophores [36]. The products were isolated in good yields and the H-5 signal of triazole (1H NMR) could be observed as a singlet at δ ≈ 7.5 ppm. Compound 11a was further converted into the corresponding bromo derivative 12 in good yield under the same

Deproto-metallation of N-arylated pyrroles and indoles using a mixed lithium–zinc base and regioselectivity-computed CH acidity relationship

• Mohamed Yacine Ameur Messaoud,
• Ghenia Bentabed-Ababsa,
• Madani Hedidi,
• Aïcha Derdour,
• Floris Chevallier,
• Yury S. Halauko,
• Oleg A. Ivashkevich,
• Vadim E. Matulis,
• Laurent Picot,
• Valérie Thiéry,
• Thierry Roisnel,
• Vincent Dorcet and
• Florence Mongin

Beilstein J. Org. Chem. 2015, 11, 1475–1485, doi:10.3762/bjoc.11.160

• antiproliferative activity, with no significant difference between the pyrrole and indole derivatives. Conclusion Unlike other azoles such as pyrazole and triazoles [37][38][40], pyrrole and indole do not possess any atom capable of coordinating metals. As a consequence, the corresponding CH acidities in THF

• solution, which were calculated using a continuum solvation model, better help in rationalizing the outcome of the deproto-metallation reactions. In addition, whereas N-(4-substituted phenyl)pyrazoles and -triazoles (e.g., with methoxy as substituent, Figure 7) can be deprotonated at C2’ for the same

Synthesis and spectroscopic properties of β-triazoloporphyrin–xanthone dyads

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2015, 11, 1434–1440, doi:10.3762/bjoc.11.155

• transfer between the porphyrin part and the attached subunit. Moreover, the 1,4-disubstituted triazoles are found to be very useful for various applications including modification of cell surfaces [25], synthesis of new glycoproteins [26], specific labeling of virus particles [27] and synthesis of

• ] including anti-oxidative [35], antihypertensive [36], anti-inflammatory [37] and antiplatelet agents [38]. They have also been used as fluorophores and exhibited good fluorescence properties when attached to a triazole ring [39][40]. Owing to the biological significance of porphyrins, 1,2,3-triazoles and

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

• triazoles. A streamlined two-step approach to this uncommon class of hindered triazoles will accelerate exploration of their therapeutic potential. The superior activity of copper(II) triflate in the formation of triazoles from sensitive alkyne substrates extends to simple terminal alkynes. Keywords: azide

• ; copper catalysis; multicomponent reactions; tetrasubstituted carbon; triazole; Introduction 1,2,3-Triazoles demonstrate wide spread application in biological systems and drug development [1][2][3][4][5][6][7][8][9][10][11][12]. Copper-catalyzed azide–alkyne cycloadditions (CuAAC) regioselectively

• introduce a wide variety of substituents on 1,4-disubstituted 1,2,3-triazoles from the organic azide or terminal alkyne starting materials [1][2]. These Huisgen reactions [13] facilitate rapid drug screening by allowing for tracking in biological systems and the exploration of structure-activity

The reactions of 2-ethoxymethylidene-3-oxo esters and their analogues with 5-aminotetrazole as a way to novel azaheterocycles

• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess and
• Viktor I. Saloutin

Beilstein J. Org. Chem. 2015, 11, 385–391, doi:10.3762/bjoc.11.44

• preparation of compound 11 in the reaction of ester 1f with 5-AT was unexpected, because it is known that ester 1f interacts with 3-amino-1,2,4-triazole in refluxing ethanol [8] and with substituted 5-amino-1,2,4-triazoles in acetic acid [34] to afford triazolo[1,5-a]pyrimidines. However, we did not observe

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

• Natalia A. Danilkina,
• Petr S. Vlasov,
• Semen M. Vodianik,
• Andrey A. Kruchinin,
• Yuri G. Vlasov and
• Irina A. Balova

Beilstein J. Org. Chem. 2015, 11, 373–384, doi:10.3762/bjoc.11.43

• ][17][18]. Moreover, various species of` PAEs with quinoline [19][20], quinoxaline [21][22], thiadiazole [17][23], carbazole [18][24], 1,2,4-triazoles [25], thiazole [26] and azametallocyclic [27] units incorporated into a polymer chain have been described. Since ligands based on pyridazine rings can

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

• assumes particular interest according to its easily access and the well-known biological activity of many derivatives. In these last years, in fact, triazoles have gained considerable attention in medicinal chemistry, bioconjugation, drug-delivery, and materials science [33][34][35][36][37][38]. Moreover

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

• describe a one-pot protocol for the synthesis of a novel series of polycyclic triazole derivatives. Transition metal-catalyzed decarboxylative CuAAC and dehydrogenative cross coupling reactions are combined in a single flask and achieved good yields of the respective triazoles (up to 97% yield). This

• 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

The unexpected influence of aryl substituents in N-aryl-3-oxobutanamides on the behavior of their multicomponent reactions with 5-amino-3-methylisoxazole and salicylaldehyde

• Volodymyr V. Tkachenko,
• Elena A. Muravyova,
• Sergey M. Desenko,
• Oleg V. Shishkin,
• Svetlana V. Shishkina,
• Dmytro O. Sysoiev,
• Thomas J. J. Müller and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2014, 10, 3019–3030, doi:10.3762/bjoc.10.320

• spectrum of biological activity [5][6], which led to choose acetoacetamides as perspective methylene-active compounds for further studies of multicomponent reactions. The interactions of 3-oxobutanamides with aldehydes and a number of aminoazoles, namely 3-amino-1,2,4-triazoles [7][8][9][10][11], 5

• azoloazine with high chemo- and regioselectivity [11][13][14][15]. In particular, three-component heterocyclizations involving 3-amino-1,2,4-triazoles or 4-substituted 5-aminopyrazoles yielded either 4,5,6,7-tetrahydroazolo[1,5-a]pyrimidine-6-carboxamides under ultrasonication at room temperature (kinetic

Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

• Anxo Fernández-Ferreiro,
• Noelia Fernández Bargiela,
• María Santiago Varela,
• Maria Gil Martínez,
• Maria Pardo,
• Antonio Piñeiro Ces,
• José Blanco Méndez,
• Miguel González Barcia,
• Maria Jesus Lamas and
• Francisco.J. Otero-Espinar

Beilstein J. Org. Chem. 2014, 10, 2903–2911, doi:10.3762/bjoc.10.308

• ]. Specifically, azole-based medications, which include imidazoles (e.g., miconazole, clotrimazole, and ketoconazole) and triazoles (e.g., fluconazole, itraconazole, posaconazole, and voriconazole), inhibit ergosterol synthesis in the cell wall [4]. Fluconazole is considered to be a good therapeutic option for

Synthesis of aromatic glycoconjugates. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2014, 10, 2453–2460, doi:10.3762/bjoc.10.256

• focus was on glycosylated amino acid building blocks derived from aspartic acid and from the PNA-like N-(2-aminoethyl)glycine (AEG) backbone to which the sugar moieties were attached through either simple alkyl chains [5][6], amino alcohols [7][8] or 1,2,3-triazoles [9][10][11]. These building blocks

Derivatives of the triaminoguanidinium ion, 3. Multiple N-functionalization of the triaminoguanidinium ion with isocyanates and isothiocyanates

• Jan Szabo,
• Kerstin Karger,
• Nicolas Bucher and
• Gerhard Maas

Beilstein J. Org. Chem. 2014, 10, 2255–2262, doi:10.3762/bjoc.10.234

• (arylideneamino)- and tris(alkylideneamino)guanidinium salts [7][8][9]; these were the first examples of a threefold symmetrical functionalization of the triaminoguanidinium ion. On the other hand, reactions of triaminoguanidinium salts with carboxylic acids generated 4-amino-3-hydrazinyl-1,2,4-triazoles [10][11

• ]. Diversely substituted 1,2,4-triazoles were also obtained from reactions with cyanogen bromide [12], CS2/NaOH [12] and isothiocyanates [13]. In all these cases, cyclization took place after one or two of the three branches of the triaminoguanidinium ion had been functionalized. Reactions of TAG-Cl (1) with

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• synthesis of 1-alkoxy-1H-benzo[d][1,2,3]triazoles. Three possible mechanisms for the reaction of BOP with oxygen nucleophiles. Possible products in the [18O]-labeling experiments. Two possible products from the reaction of At-OTs with MeOH. Synthesis of acyclic nucleoside-like compounds. Formation of Bt-OR

Synthesis of new, highly luminescent bis(2,2’-bithiophen-5-yl) substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole

• Anastasia S. Kostyuchenko,
• Vyacheslav L.Yurpalov,
• Aleksandra Kurowska,
• Wojciech Domagala,
• Adam Pron and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2014, 10, 1596–1602, doi:10.3762/bjoc.10.165

• that 1,3,4-oxadiazoles [26], 1,3,4-thiadiazole [27] and 1,2,4-triazoles [28][29][30] can be obtained from diacylhydrazines. Thus, 11 and 12 were converted to 2,5-bis(3-decyl-2,2'-bithiophen-5-yl)-1,3,4-oxadiazole (13) and 2,5-bis[4-(hexyloxy)-2,2'-bithiophen-5-yl]-1,3,4-oxadiazole (14) by the reaction

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

• the ease of purification, 1,4-disubstituted-1,2,3-triazoles, the regiospecific product of this reaction, exhibit similarities to the ubiquitous amide moiety found in nature. However, unlike amides, the triazole moiety proved to be robust and resistant to chemical and enzymatic cleavage [17][18][19][20

• parent precursors [33][34][35][36][37][38][39]. Over the years, many structural analogues of this class of antibiotics have been synthesized. In addition, triazoles are considered as peptidic linkage surrogates. Surprisingly, despite the enormous research interests associated with their synthesis, only a

Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

• Zong Guan,
• Jan C. Namyslo,
• Martin H. H. Drafz,
• Martin Nieger and
• Andreas Schmidt

Beilstein J. Org. Chem. 2014, 10, 832–840, doi:10.3762/bjoc.10.79

• NHCs of indazole which have been generated and applied in heterocyclic synthesis (vide infra) as well as in complex chemistry [13]. Undoubtedly the N-heterocyclic carbenes of imidazole, imidazoline and the triazoles play the most important roles as ligands in metal-organic chemistry [14] or as

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• , oxazoles, thiazoles and triazoles incorporated into peptide structures will be described. Pyrrolidines 2-substituted pyrrolidine-based dipeptide mimics were obtained from an Ugi-4CR followed by a Pd-catalyzed Sn2 cyclization as described by Banfi et al. [51] . Herein, the Ugi reaction provided a small

• lactams (81, 46% over the two steps, Scheme 24). In addition, an even shorter route by utilizing three olefinic Ugi-substrates was also reported. Herein, the ring closing step included a double RCM and resulted in an equal amount of both products 83a and 83b (ratio 1:1) [75][76]. Triazoles The replacement

• of amide bonds by 1,2,3-triazoles, especially the 1,4-disubstituted isomer, provided a wide variety of biological active peptidomimetics. Peptidomimetics containing these triazole cores can serve as blood components [77], anticancer medications [78], inhibitors of cysteine [79] and HIV-1 proteases

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• but-2-ynedioate and phenyl azide at 100 °C in a sealed tube and suggested that regioisomeric triazoles were formed [1]. However, it was only in the 1960s that Huisgen recognized this type of reaction for its generality, scope and mechanism [2][3][4][5], and coined the term 1,3-dipolar cycloaddition

• . The classical thermal Huisgen cycloaddition of organoazides and alkynes proceeds very slowly even at high temperatures, and gives a mixture of 1,4- and 1,5-disubstituted 1,2,3-triazoles (Scheme 1). In 2002, the groups of Meldal and Sharpless independently discovered a copper-catalyzed variant of

• Huisgen’s azide–alkyne cycloaddition (CuAAC reaction). In fact, the catalytic effect of copper ions had first been mentioned by L’Abbé in 1984 [7], but had henceforth been overlooked until Meldal presented a copper(I)-catalyzed solid-phase synthesis of 1,2,3-triazoles. In this procedure, the terminal alkyne