Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbene-methylene-3-sydnones and their synthesis

• Kristina Butković,
• Željko Marinić,
• Krešimir Molčanov,
• Biserka Kojić-Prodić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2011, 7, 1663–1670, doi:10.3762/bjoc.7.196

• hybrids of a number of mesomeric ionic structures (Figure 1). One of the most characteristic reactions of sydnones is the intermolecular 1,3-dipolar cycloaddition. In the presence of acetylenic or ethylenic dipolarophiles, sydnones undergo cycloaddition reactions, which can be induced thermally [4][6][7

• azomethine imines. Intramolecular 1,3-dipolar cycloadditions of sydnone derivatives have not been as thoroughly investigated, and so far only a few examples are known [18][19][20]. Photochemically induced intramolecular 1,3-dipolar cycloadditions have been studied on 3,4-disubstituted sydnone derivatives [18

• such a system, where two chromophores, stilbene and sydnone, are divided by a methylene bridge, an intramolecular 1,3-dipolar cycloaddition and the formation of diverse polycyclic compounds could be expected. Herein we describe, for the first time, the synthesis of cis- and trans-3-(stilbenylmethyl

Efficient synthesis of 1,3-diaryl-4-halo-1H-pyrazoles from 3-arylsydnones and 2-aryl-1,1-dihalo-1-alkenes

• Yiwen Yang,
• Chunxiang Kuang,
• Hui Jin,
• Qing Yang and
• Zhongkui Zhang

Beilstein J. Org. Chem. 2011, 7, 1656–1662, doi:10.3762/bjoc.7.195

• based on the condensation of hydrazines with 1,3-dicarbonyl compounds or their equivalents. However, the 1,3-dipolar cycloaddition offers a more convenient synthetic route. Sydnones are easily accessible aromatic compounds and versatile synthetic intermediates. They can be used as unusual, alternative

• unknown, as is the direct formation of 4-halopyrazoles through the [3 + 2] dipolar cycloaddition of sydnones. In the present study, a convenient and efficient synthesis of a series of new 1,3-diaryl-4-halo-1H-pyrazoles 3 in moderate to excellent yields is reported. The route employed involves 1,3-dipolar

• stirred in the dark in a sealed tube maintained at 140 °C in an oil bath. After 16 h, the product 3a was isolated in 72% yield. The effects of different bases, molar ratios of 1a to 2a, solvents, and temperatures on the formation of 3a were investigated. The optimization of the 1,3-dipolar cycloaddition

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• -type cycloadditions The copper-catalyzed Huisgen-type cycloaddition (CuAAC) is a general and useful method for the synthesis of 1,4-disubstituted-1,2,3-triazoles and is based on the 1,3-dipolar cycloaddition of alkynes and azides [28]. Besides Cu(I) sources also Cu(0) sources, such as copper wire [29

Recent developments in gold-catalyzed cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2011, 7, 1075–1094, doi:10.3762/bjoc.7.124

• -catalyzed synthesis of polycyclic, fully substituted furans from 1-(1-alkynyl)cyclopropyl ketones [45]. Gold-catalyzed 1,3-dipolar cycloaddition of 2-(1-alkynyl)-2-alken-1-ones with nitrones [47]. Enantioselective 1,3-dipolar cycloaddition of 2-(1-alkynyl)-2-alken-1-ones with nitrones [48]. Gold-catalyzed

• 1,3-dipolar cycloaddition of 2-(1-alkynyl)-2-alken-1-ones with α,β-unsaturated imines [49]. Gold-catalyzed (4 + 3) cycloadditions of 1-(1-alkynyl)oxiranyl ketones [50]. (3 + 2) Cycloaddition of gold-containing azomethine ylides [52]. Gold-catalyzed generation and reaction of azomethine ylides [53

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• . Pyrazoles are also useful intermediates for many industrial products and it is, therefore, not surprising that many synthetic methods have been developed for the preparation of such heterocyclic systems, for example, through 1,3-dipolar cyclo-additions of diazo compounds and the direct condensation of 1,3

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

• María Martín-Rodríguez,
• Carmen Nájera,
• José M. Sansano,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2011, 7, 988–996, doi:10.3762/bjoc.7.111

• , Apdo. 1072, E-20018 San Sebastián, Spain 10.3762/bjoc.7.111 Abstract The synthesis of a GSK 2nd generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and

• origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial. Keywords: BINAP; 1,3-dipolar cycloaddition; gold; HCV

• synthesis of the endo-pyrrolidine core of 5 is the key step for the preparation of these antiviral agents, and can be efficiently achieved by a 1,3-dipolar cycloaddition (1,3-DC) between the corresponding azomethine ylide and an alkyl acrylate [14][15][16][17][18] (Scheme 1). The first synthesis of racemic

High chemoselectivity in the phenol synthesis

• Matthias Rudolph,
• Melissa Q. McCreery,
• Wolfgang Frey and
• A. Stephen K. Hashmi

Beilstein J. Org. Chem. 2011, 7, 794–801, doi:10.3762/bjoc.7.90

• intermediates A or B. Apart from intermolecular trapping [26][27][28][29][30][31][32][33], intramolecular trapping of such carbenoids has also been reported [34]. One option would be to offer a competing carbonyl group, to produce a carbonyl ylide, which could then undergo a 1,3-dipolar cycloaddition [35]. The

• b). The latter would form intermediate H, which could then either afford product 17 via intramolecular 1,3-dipolar cycloaddition with the olefin, or could form the diene 19 by proton migration. The synthesis of 16 was only possible by a 9-step sequence (Scheme 8). The starting point was a Claisen

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• activation of the cyclopropene, cation 55 is formed. C–C bond cleavage of the cyclopropyl ring followed by a Friedel–Crafts reaction affords, after recovery of aromaticity, the observed products [47]. 4 Ring expansions involving annulation reactions Diels–Alder, [1,3]-dipolar-, [2 + 2]- and [4 + 3

• formation of the 1,4-furan dipole (Scheme 21). In fact, a resonance structure of 60 can be envisaged entailing a gold–carbene and a carbonyl ylide 63. Upon 1,3-dipolar cycloaddition with the alkoxy vinyl ether, bridged bicycle 64 is formed. 1,2-Alkyl migration and bridge opening produces a spiro cation 66

Advances in synthetic approach to and antifungal activity of triazoles

• Kumari Shalini,
• Nitin Kumar,
• Sushma Drabu and
• Pramod Kumar Sharma

Beilstein J. Org. Chem. 2011, 7, 668–677, doi:10.3762/bjoc.7.79

• which an azide and an alkyne undergo a 1,3-dipolar cycloaddition reaction in the presence of a catalyst such as copper (Scheme 1) or ruthemium (Scheme 2) [27]. Some new synthetic methods for 1,2,3-triazoles are given below (Scheme 3, Scheme 4) [28][29]. Structure activity relationships have revealed

• occupies the most important place in the treatment of fungal diseases. The triazole derivatives noted below were synthesized by various groups and show antifungal activity. Novel 1,2,3-triazole-linked with β-lactam–bile acid conjugates were prepared via 1,3-dipolar cycloaddition reactions of azido β

• ]. Holla et al. synthesized triazole derivatives by the 1,3-dipolar cycloaddition reaction of 4-azido-8-trifluoromethylquinoline with ethyl acetoacetate and acetylacetone, respectively, and tested for antifungal activity against Candida albicans. Among the various synthesized compounds, 1-(1-(8

Unusual behavior in the reactivity of 5-substituted-1H-tetrazoles in a resistively heated microreactor

• Bernhard Gutmann,
• Toma N. Glasnov,
• Tahseen Razzaq,
• Walter Goessler,
• Dominique M. Roberge and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2011, 7, 503–517, doi:10.3762/bjoc.7.59

• source and acetic acid (AcOH) as the reagent/catalyst in a NMP/H2O solvent mixture [25]. These 1,3-dipolar cycloadditions which involve in situ generated free hydrazoic acid (HN3) were performed on small scale (≈1 mL) at 220 °C in a microwave batch reactor with reaction times of 4–15 min, depending on

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• pyrazole [74]. However, preparation of the alkyne intermediates involves a number of steps and often requires extensive column chromatography, which makes it an unattractive method for synthesis on a larger scale (Scheme 48). A novel 1,3-dipolar cycloaddition between a nitrile imide 244 and an

Rh-Catalyzed rearrangement of vinylcyclopropane to 1,3-diene units attached to N-heterocycles

• Franca M. Cordero,
• Carolina Vurchio,
• Stefano Cicchi,
• Armin de Meijere and
• Alberto Brandi

Beilstein J. Org. Chem. 2011, 7, 298–303, doi:10.3762/bjoc.7.39

• domino 1,3-dipolar cycloaddition/thermal rearrangement sequence, were converted by Wittig methylenation to the corresponding vinylcyclopropanes (VCPs), which underwent rearrangement to 1,3-dienes in the presence of the Wilkinson Rh(I) complex under microwave heating. The previously unexplored Rh(I

• so that the various specific cyclopropane transformations can be used as a synthetic tool. In recent years we have shown that 1,3-dipolar cycloadditions of nitrones 1 to the highly strained alkene bicyclopropylidene (BCP, 2) [5][6][7] afford spirocyclopropanated isoxazolidines 3 [8][9] which, on

• shift in the cyclopropanated 1,6-diradical intermediate, which in this case is probably facilitated by the enhanced mobility of the benzylic hydrogen and by the formation of the conjugationally stabilized imine 9 [11]. The 1,3-dipolar cycloaddition/thermal rearrangement domino reaction of BCP (2) with

Total synthesis of (±)-coerulescine and (±)-horsfiline

• Mukund G. Kulkarni,
• Attrimuni P. Dhondge,
• Sanjay W. Chavhan,
• Ajit S. Borhade,
• Yunnus B. Shaikh,
• Deekshaputra R. Birhade,
• Mayur P. Desai and
• Nagorao R. Dhatrak

Beilstein J. Org. Chem. 2010, 6, 876–879, doi:10.3762/bjoc.6.103

• include the following oxidative rearrangements: lead tetraacetate [3], sodium tungstate [11], tert-butyl hypochlorite [12] and N-bromosuccinimide [13]. Other approaches involve the Mannich reaction [14], ring expansion reactions [15][16], 1,3-dipolar [3 + 2] cycloadditions [17][18][19], intramolecular

Calix[4]arene-click-cyclodextrin and supramolecular structures with watersoluble NIPAAM-copolymers bearing adamantyl units: “Rings on ring on chain”

• Bernd Garska,
• Monir Tabatabai and
• Helmut Ritter

Beilstein J. Org. Chem. 2010, 6, 784–788, doi:10.3762/bjoc.6.83

• -cyclodextrin combi-receptor (4) was synthesized via copper-catalyzed Huisgen 1,3-dipolar cycloaddition. Investigations of the interactions with an adamantyl moiety containing copolymer have been carried out, showing the existence of a supramolecular structure. Due to deprotonation of the calixarene moieties at

Addition of lithiated enol ethers to nitrones and subsequent Lewis acid induced cyclizations to enantiopure 3,6-dihydro-2H-pyrans – an approach to carbohydrate mimetics

• Fabian Pfrengle and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2010, 6, No. 75, doi:10.3762/bjoc.6.75

• further diversification of our pyran derivatives, e.g., by 1,3-dipolar cycloaddition leading to isoxazole derivatives [22] or, by addition of nucleophiles to this electrophilic unit [9]. Compounds 8 and 21 proved to be excellent precursors for the stereoselective preparation of enantiopure aminopyrans

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• surface of the nanoparticles Results and Discussion Synthesis and characterization of the polymer surfactants Besides well-known functionalization of anhydride-based copolymers, the grafting of carbohydrate moieties on a polymer backbone by Huisgen [2 + 3] cycloaddition (CuI-catalyzed 1,3-dipolar

An expedient and new synthesis of pyrrolo[1,2-b]pyridazine derivatives

• Rajeshwar Reddy Sagyam,
• Ravinder Buchikonda,
• Jaya Prakash Pitta,
• Himabindu Vurimidi,
• Pratap Reddy Padi and
• Mahesh Reddy Ghanta

Beilstein J. Org. Chem. 2009, 5, No. 66, doi:10.3762/bjoc.5.66

• cycloaddition of dimethyl acetylenedicarboxylate to the Reissert compound of pyridazine [20], the 1,3-dipolar cycloaddition of pyridazinium dichloromethylide generated by the carbene method [21], and the cycloaddition of alkylidene cyclopropane derivatives to pyridazine in the presence of Pd(PPh3)4 [22

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• the planned construction of the aziridine by tandem SN2 displacement. Exploiting the facial selectivity of compound 38, the direct introduction of an aziridine equivalent was attempted by 1,3-dipolar cycloaddition of an alkyl azide. As Frank noted, cycloaddition of azides to 3H-pyrrolo [1,2-a]indoles

Dimerization of propargyl and homopropargyl 6-azido- 6-deoxy- glycosides upon 1,3-dipolar cycloaddition

• Nikolas Pietrzik,
• Daniel Schmollinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2008, 4, No. 30, doi:10.3762/bjoc.4.30

• Nikolas Pietrzik Daniel Schmollinger Thomas Ziegler Institute of Organic Chemistry, University of Tuebingen, Auf der Morgenstelle 18, 72076 Tuebingen, Germany. 10.3762/bjoc.4.30 Abstract Copper-catalyzed, thermal or microwave promoted 1,3-dipolar cycloaddition (Click Reaction) of 2-propynyl and 3

• -triazoles which are known to be easily generated through a copper-catalyzed 1,3-dipolar cycloaddition of an organic azide and an alkynyl derivative (Click Reaction) [5][6][7]. For review articles on copper-catalyzed Click Reactions see references [8][9][10][11]. Recently, we applied this approach to a

• series of 1,2,3-triazole containing per-O-acetyl-glycosides which were prepared by copper-catalyzed 1,3-dipolar cycloaddition either between fully acetylated propargyl 1-thio-glycosides and t-butyl (S)-4-azido-3-fluorenylmethyloxycarbamido-butyrate or between Fmoc-L-Asp(OtBu)-propargyl amide and 2,3,4,6

Synthesis of 2-substituted 9-oxa-guanines {5-aminooxazolo[5,4-d]pyrimidin- 7(6H)-ones} and 9-oxa-2-thio- xanthines {5-mercaptooxazolo[5,4-d]pyrimidin- 7(6H)-ones}

• Subrata Mandal,
• Wen Tai Li,
• Yan Bai,
• Jon D. Robertus and
• Sean M. Kerwin

Beilstein J. Org. Chem. 2008, 4, No. 26, doi:10.3762/bjoc.4.26

• preparation of a series of 2-substituted 5-aminooxazolo[5,4-d]pyrimidin-7(6H)-ones and related 5-thio-oxazolo[5,4-d]pyrimidines is described, including analogs suitable for further elaboration employing “click” chemistry utilizing copper-catalyzed Huisgen 1,3-dipolar cycloadditions. Two of the compounds

• preparation of analogs suitable for further elaboration, for example by “click” chemistry employing copper-catalyzed Huisgen 1,3-dipolar cycloadditions [18]. Results and Discussion Our previous route [5] to 8-methyl-9-oxa-guanine (2a) involved the thermal cyclodehydration of 5-(acetylamino)-2-amino-4,6

Synthesis of new triazole- based trifluoromethyl scaffolds

• Michela Martinelli,
• Thierry Milcent,
• Sandrine Ongeri and
• Benoit Crousse

Beilstein J. Org. Chem. 2008, 4, No. 19, doi:10.3762/bjoc.4.19

• derivatives to afford 1,4-disubstituted 1,2,3-triazoles through a Huisgen 1,3-dipolar cycloaddition. The reaction is catalyzed by a Cu(I) species in acetonitrile, and the corresponding products are obtained in good yields. This process thus offers an entry to new trifluoromethyl peptidomimetics as interesting

• trifluoromethyl groups on the conformation of peptidomimetics, we decided to explore the preparation of trifluoromethyl triazole derivatives. Herein we turn our attention to the synthesis of new triazoles from trifluoromethyl propargylamines using the Huisgen 1,3-dipolar cycloaddition [27][28][29]. Results and

• Discussion The synthetic approach depicted in Scheme 1 shows that the desired compounds could be easily obtained via a 1,3-dipolar cycloaddition from the corresponding propargylamines which are obtained using an efficient procedure from the trifluoromethyl imines previously described by our group [30][31][32

Synthesis of densely functionalized enantiopure indolizidines by ring- closing metathesis (RCM) of hydroxylamines from carbohydrate- derived nitrones

• Marco Bonanni,
• Marco Marradi,
• Francesca Cardona,
• Stefano Cicchi and
• Andrea Goti

Beilstein J. Org. Chem. 2007, 3, No. 44, doi:10.1186/1860-5397-3-44

• . [5][6][7][8][9][10][11][12][13][14][15][16][17][18] We accomplished the total syntheses of some indolizidine alkaloids and of several non-natural analogues employing chiral nitrones as key intermediates, either as dipolarophiles in 1,3-dipolar cycloaddition chemistry [19][20] or as electrophiles in

Aroylketene dithioacetal chemistry: facile synthesis of 4-aroyl- 3-methylsulfanyl- 2-tosylpyrroles from aroylketene dithioacetals and TosMIC

• H. Surya Prakash Rao and
• S. Sivakumar

Beilstein J. Org. Chem. 2007, 3, No. 31, doi:10.1186/1860-5397-3-31

• heterocyclic systems, examples of their participation in the cycloaddition reactions are rare. In continuation of our interest on ketene acetals [5][6][7] we considered that 1,3-dipolar cycloaddition of the anion generated from the von Leusen's reagent (p-tolylsulfonyl)methyl isocyanide (TosMIC) 2 to AKDTAs 1