Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• .14.246 Abstract A new metal-free one-pot three-component procedure towards fully substituted triazolochromenes has been developed, starting from commercially available materials. Salicylaldehydes and nitroalkenes were reacted under solvent-free conditions, followed by a 1,3-dipolar cycloaddition of the

• prove the plausibility of the one-pot three-component reaction, we commenced our trials with the synthesis and isolation of 3-nitro-2H-chromene (3) as reported in the literature [15], followed by the 1,3-dipolar cycloaddition of the nitroalkene moiety with organic azides. We based the 1,3-dipolar

• -nitrochromenes. Because our first step is best performed solvent-free, we opted to try our own optimized solvent-free conditions for the in situ syntheses of 3-nitro-2H-chromenes, followed by the 1,3-dipolar cycloaddition in a reaction vial. Despite being a two-pot procedure, purification of the intermediate 3

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing 100050, China 10.3762/bjoc.14.75 Abstract A straightforward and one-pot synthesis of pyrrolo[3,4-c]pyrrole-1,3-diones via Ag(I)-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with N-alkyl maleimide, followed by readily

• substrates. It is conceivable that this efficient construction method for privileged pyrrole scaffolds could deliver more active compounds for medicinal chemistry research. Keywords: azomethine ylides; 1,3-dipolar cycloaddition; one-pot synthesis; polysubstituted pyrroles; pyrrolo[3,4-c]pyrrole-1,3-diones

• methods have been reported till now to synthesize pyrroles and pyrrole containing analogs [6]. In the past decade, 1,3-dipolar cycloaddition has become a fundamental synthetic method for the construction of nitrogen-containing five-membered heterocycles including pyrroles. It is worth to note that

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• azide–alkyne Huisgen cycloaddition AuNP surface modification using NCAAC The azide–alkyne Huisgen cycloaddition (AAC) is a 1,3-dipolar cycloaddition between an organic azide and an alkyne that gives triazole products [37][38]. The non-catalysed azide–alkyne Huisgen cycloaddition (NCAAC) is very slow

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• reacted easily in a SN2 reaction to give a more functionalized molecule. For example, treatment of the chlorinated monofluoroalkene with NaN3 provided the corresponding N3-containing monofluoroalkene. The azide group underwent a 1,3-dipolar cycloaddition to give a 1,2,3-triazole, which is also a peptide

Rh(II)-mediated domino [4 + 1]-annulation of α-cyanothioacetamides using diazoesters: A new entry for the synthesis of multisubstituted thiophenes

• Jury J. Medvedev,
• Ilya V. Efimov,
• Yuri M. Shafran,
• Vitaliy V. Suslonov,
• Vasiliy A. Bakulev and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2017, 13, 2569–2576, doi:10.3762/bjoc.13.253

• reaction with N-phenyl maleimide, gives rise to formation of S-containing heterocycles by 1,3-dipolar cycloaddition [35]. However, to the best of our knowledge, there are no literature data on analogous intramolecular reactions of C=S ylides involving thiocarbonyl and any other nucleophilic group within

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• reactions were planned between phenylacetylene and compounds 6a–c. The 1,2,3-triazole synthesis from the 1,3-dipolar cycloaddition reaction between 6a–c and terminal alkynes catalyzed by copper salts (CuAAC) [41][42][43] confirms that the reaction passes through an azide intermediate. In addition to mild

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• methine C-3 protons displayed in a 1H,1H-NOESY spectrum of 4 (Figure S10 in Supporting Information File 1). Compound 4 was then submitted to Cu(I)-catalyzed 1,3-dipolar cycloaddition with selected halogen-substituted and non-substituted aromatic azides to yield target N-heterocyclic hybrids 5–8 containing

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• -Triazoles have important applications in pharmaceutical chemistry [150] and traditionally they are prepared by 1,3-dipolar cycloaddition reactions at high temperature, long reaction times and produce low yield with multiple products [151]. In 2013, Ranu and co-workers reported mechanochemical synthesis of

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• support (Scheme 3) [42]. Owing to the symmetrical structure of the support, NMR and mass spectroscopic characterization is possible at any stage of the chain assembly. The 3´-terminal nucleoside was immobilized to this support as a 3´-O-(4-pentynoyl) derivative by Cu(I)-catalyzed 1,3-dipolar cycloaddition

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• compound is shown in Scheme 1, part B. Propargyl-ChL [35] was introduced into Huisgen copper-catalyzed 1,3-dipolar cycloaddition [36] (CuAAC) with BODIPY 3. This microwave-assisted reaction catalyzed by CuSO4·5H2O, sodium ascorbate and a catalytic amount of TBTA (tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• blocks were coupled via 1,3-dipolar cycloaddition (click reaction) iteratively through the development of a greener base-free Cu(I)-catalyzed azide–alkyne cycloaddition reaction. The cycloadducts were then converted to macrocycles by Ru-catalyzed cyclization reaction using greener and non-hazards

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• and a high degree of deuterium incorporation were achieved. The procedure was applied for several 4-R-1-aminopyridinium cations (R = H, Me, OMe). Keywords: deuteration; 1,3-dipolar cycloaddition; pyrazolo[1,5-a]pyridine; 1,2,4-triazolo[1,5-a]pyridine; Introduction Isotopically labeled compounds find

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• as for the non-methylated derivative [21]. Then, the 1,3-dipolar cycloaddition reaction of 6 with benzyl azide in toluene at 70 °C led to a mixture of regioisomeric triazoles 7 in a 42:58 ratio. The removal of all protecting groups was achieved by treatment of compounds 7 with ammonia followed by

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• most attractive way for their preparation is the thermal 1,3-dipolar cycloaddition of alkynes and azides, introduced by Huisgen which usually gives rise to a mixture of 1,4 and 1,5-isomers [16][17][18][19]. More recently, transition metal catalysts based on copper, ruthenium, silver and iridium salts

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• were obtained in good yields by regiospecific 1,3-dipolar cycloaddition reactions between aromatic nitrile oxides, generated in situ from the corresponding hydroxyimidoyl chlorides, with non-symmetrical activated alkynes in the presence of catalytic amounts of copper(I) iodide. Effects of 3,5

• -disubstituted isoxazoles on nitric oxide and reactive oxygen species generation in Arabidopsis tissues was studied using specific diaminofluoresceine dyes as fluorescence indicators. Keywords: chemical elicitor; 1,3-dipolar cycloaddition; isoxazole; nitric oxide; nitrile oxide; reactive oxygen species

• synthetic approaches towards the isoxazole core include the reactions of hydroxylamine with aryl-β-diketones [20], α,β-unsaturated carbonyl compounds [21], or α,β-unsaturated nitriles [22], and 1,3-dipolar cycloaddition reactions between alkenes or alkynes and nitrile oxides [23][24][25]. Nitrile oxides are

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• cells. Keywords: dyes; fluorescence; nucleic acid; oligonucleotide; Introduction The “click”-type reactions [1], in particular the 1,3-dipolar cycloaddition between alkynes and azides (CuAAC) is a broadly applied strategy for postsynthetic oligonucleotide modification since both reactive groups are

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• -pot multicomponent synthesis. The method uses the 1,3-dipolar cycloaddition reaction between N-alkylvinylindole/indazole and azomethine ylides, prepared in situ from cyclic/acyclic amino acids. The 1,3-dipolar cycloaddition proceeds efficiently under thermal conditions to afford the regio- and

• of biological importance [1][2]. The regio- and stereoselective construction of spiro compounds by utilizing the 1,3-dipolar cycloaddition reaction of azomethine ylides has been reported [3][4][5][6]. However, unlike the previous reports, the present method is concise and facilitates the one-pot

• synthesis of multifunctionalized spiranes. The earlier works reveal the use of different reaction conditions to prepare functionalized spiroindane, spiropyrolidine, spiropyrrolizidine and spirooxindole derivatives. Among them, the 1,3-dipolar cycloaddition based route is preferred due to multiple advantages

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• Farmaco, Università di Catania, Viale A. Doria, 95100 Catania, Italy Dipartimento di Chimica, Università di Pavia, Via Taramelli 12, 27100 Pavia, Italy 10.3762/bjoc.12.278 Abstract A series of spiro[isoindole-1,5-isoxazolidin]-3(2H)-ones has been synthesized by 1,3-dipolar cycloaddition of N

• be linked to the inhibition of the protein–protein p53-MDM2 interaction. Docking measurements support the biological data. Keywords: antitumor agents; DFT studies; 1,3-dipolar cycloaddition; docking studies; spiro-compounds; Introduction The p53 tumor suppressor protein is a transcriptional factor

• construction of the spiro[isoxazolidin-isoindolinone] system. The synthetic scheme (Figure 2) exploits the strategy of the 1,3-dipolar cycloaddition of nitrones on the substrate isoindolin-3-methylene-1-one 2, obtained by a recent methodology of a PdI2 catalyzed aminocarbonylation-N-heterocyclization of 2

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• Huisgen 1,3-dipolar cycloaddition between N-(2-azidoethyl)phthalimide and the alkyne terminal of pyEDOT under ultrasound conditions in 73% yield. Detailed synthetic routes are presented in Supporting Information File 1. Figure 1a shows the cyclic voltammograms (CVs) for electrochemical polymerization of

Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis

• Florin Albota,
• Mino R. Caira,
• Constantin Draghici,
• Florea Dumitrascu and
• Denisa E. Dumitrescu

Beilstein J. Org. Chem. 2016, 12, 2503–2510, doi:10.3762/bjoc.12.245

• other metals and represent a versatile tool for obtaining hybrid heterocycles with properties that are useful for the development of new advanced materials and for medicinal purposes [1][2][3][4]. Recently, we obtained, by 1,3-dipolar cycloaddition reactions of sydnone-ylides as bis(1,3-dipoles) with

• interesting chemical reactions of sydnones are their electrophilic substitution at C-4 and their participation in 1,3-dipolar cycloaddition reactions with olefinic and acetylenic dipolarophiles to form pyrazoles and functional transformation at C-4 [20][21][22][23][24][25][26]. Herein we present the synthesis

• of indolizines 4 (Figure 1) with the indolizine directly attached to C-4 of a sydnone ring by the indolizine Chichibabin approach. In addition, the new indolizine structures 5, connected through a keto group to a sydnone ring, were prepared by 1,3-dipolar cycloaddition reaction starting from the same

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• to demonstrate the Cu-catalyzed azide–alkyne click reaction (Huisgen 1,3-dipolar cycloaddition) and the traceless Staudinger ligation, a proof of concept study was performed for the site-selective labeling of a pharmacologically active peptide and a small organic compound. These compounds provide the

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• nitrile oxides as inverse electron-demand 1,3-dipolar cycloaddition. The found stereoselectivity of the cycloaddition is driven by the higher stability of the E-isomer of the starting enamine, whereas the regioselectivity is controlled by better orbital overlap in the transition state leading to the

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

• -triazine moieties has been developed. The method relies on a 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatin derivatives and sarcosine to 6-benzylideneimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7-diones. Keywords: azomethine ylides; cycloaddition; diastereoselectivity

• constructing complex N-heterocyclic systems in a regio and stereocontrolled fashion is the 1,3-dipolar cycloaddition of azomethine ylides to electron-deficient alkenes as dipolarophiles [2][3][4][5][6][7][8]. The in situ preparation of azomethine ylides from different carbonyl and amino components makes the

• cycloaddition one of the most valuable means of combinatorial chemistry. Such multicomponent reactions are characterized by productivity, operational simplicity, and efficiency [9][10][11][12][13]. A highly interesting class of heterocycles which is accessible through 1,3-dipolar cycloaddition reactions are

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• synthesis of 1,2,3-triazolonucleotides (1a–o, Figure 1) was envisaged using the Huisgen 1,3-dipolar cycloaddition of the azido-sugar-phosphonate key-intermediate 2 (Scheme 1) and selected commercially available alkynes. Thus, (1-azido-2,5-di-O-acetyl-3-O-benzoyl-6-deoxy-6-diethylphosphono)-β-ribo-(5S

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

• experience, these reactions are not suitable for TINA-TFO derivatives due to excessive formation of side products. Copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) as a variation of the Huisgen 1,3-dipolar cycloaddition has become a widely used conjugation method in which the stereoselective formation