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

Azobenzene-based inhibitors of human carbonic anhydrase II

• Leander Simon Runtsch,
• David Michael Barber,
• Peter Mayer,
• Michael Groll,
• Dirk Trauner and
• Johannes Broichhagen

Beilstein J. Org. Chem. 2015, 11, 1129–1135, doi:10.3762/bjoc.11.127

• -pot reaction over three steps in 25%. By diazotization of 1d and trapping the salt with TMS-azide, we obtained azido azobenzene 1e in 63% yield through a [3 + 2] and retro-[3 + 2] cycloaddition (Scheme 1b) according to the procedure of Barral et al [10]. For the Mills reaction, different nitroso

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

• the H-4a proton that resonates at 2.18 ppm as a doublet of doublet of doublets. 5’-Azido-2’-oxa-3’-aza-4’a-carbanucleosides 11 and 12 were independently engaged in a CuI-catalyzed Huisgen [3 + 2] cycloaddition reaction with a series of substituted alkynes 17, according to the procedure described by

• formation of viral plaques or virus-induced cytopathogenicity by 50% is expressed as EC50. Conclusion In summary, starting from 5’-azido-2’-oxa-3’-azanucleosides, a new series of C-5’-triazolyl-2’-oxo-3’-aza-4’a-carbanucleosides has been synthesized by using a CuI-catalyzed Huisgen [3 + 2] cycloaddition

An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• couplings [13][14], and photooxygenation reactions [15][16]. Similarly, Zheng has reported oxidatively initiated indole synthesis [17] and [3 + 2] cycloaddition [18][19] reactions using photocatalyst 2. Finally, a variety of transition metal complexes bearing bipyrazyl ligands have been prepared and

Three-component synthesis of C₂F₅-substituted pyrazoles from C₂F₅CH₂NH₂·HCl, NaNO₂ and electron-deficient alkynes

• Pavel K. Mykhailiuk

Beilstein J. Org. Chem. 2015, 11, 16–24, doi:10.3762/bjoc.11.3

• C2F5CHN2, that participates in a [3 + 2] cycloaddition with electron-deficient alkynes in dichloromethane. Keywords: cycloaddition; fluorine; pentafluoroethyl group; pentafluoroethyldiazomethane; pyrazole; Introduction Incorporation of fluorinated fragments into organic compounds might affect their

• -dicarbonyl compounds (or their synthons) with hydrazines [39][40][41][42][43][44]. In this context, novel practical methods to C2F5-pyrazoles are needed. Last year, Ma and colleagues synthesized CF3-pyrazoles by [3 + 2] cycloaddition between in situ generated CF3CHN2 and alkynes [45]. This method, however

• with C2F5CHN2 to give only 3,5-disubstituted pyrazoles. Formation of 3,4-disubstituted isomers was observed. Disubstituted alkynes behaved differently, because of controversial electronic and steric effects. According to the orbital symmetry rules, the [3 + 2] cycloaddition must lead to pyrazoles with

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

• several advantages over the classical C–C bond formation method including the stability and preparation of the starting material and the non-hazardous byproducts. In 2011, Kolarovič et al. [6] first reported the copper-catalyzed decarboxylative [3 + 2] cycloaddition reaction of 2-alkynoic acid with

• formation of 4 is described in Scheme 5. Initially alkynoic acid 2 undergoes decarboxylation to form the copper acetylide (A) in the presence of the Cu+ catalyst which is generated by the reduction of Cu2+ with sodium ascorbate. The obtained copper acetylide undergoes regioselective [3 + 2] cycloaddition

Synthesis of 2-trifluoromethylpyrazolo[5,1-a]isoquinolines via silver triflate-catalyzed or electrophile-mediated one-pot tandem reaction

• Xiaoli Zhou,
• Meiling Liu,
• Puying Luo,
• Yingjun Lai,
• Tangtao Yang and
• Qiuping Ding

Beilstein J. Org. Chem. 2014, 10, 2286–2292, doi:10.3762/bjoc.10.238

• Gynecology, Jiangxi Provincial people's Hospital, Nanchang, Jiangxi 330006, P. R. China 10.3762/bjoc.10.238 Abstract An efficient one-pot tandem cyclization/[3 + 2] cycloaddition reaction of N’-(2-alkynylbenzylidene)hydrazides with ethyl 4,4,4-trifluorobut-2-ynoate under silver triflate-catalyzed or

• electrophile-mediated conditions is described. Various trifluoromethylated pyrazolo[5,1-a]isoquinolines were afforded in moderate to excellent yield by this developed method. Keywords: [3 + 2] cycloaddition; electrophile; N’-(2-alkynylbenzylidene)hydrazide; silver triflate; tandem; Introduction Isoquinolines

• reaction of N’-(2-alkynylbenzylidene)hydrazides 1a (0.3 mmol) and ethyl 4,4,4-trifluorobut-2-ynoate (2, 0.6 mmol) using NaOAc (0.45 mmol) as base, in the presence of AgOTf (5 mol %) and 4 Å MS (75 mg) in CH2Cl2 (3 mL) at room temperature overnight. Surprisingly, the unexpected [3 + 2] cycloaddition product

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

• bioorthogonal labeling reactions that allow visualization [5][6]. Whereas in the first report on glycan labeling by this approach the ketone–hydrazide ligation was employed [7], later investigations mainly relied on the Staudinger ligation [8] and azide–alkyne [3 + 2] cycloaddition (copper-catalyzed [9][10] or

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

• 34% yield. A second [3 + 2] cycloaddition with a different glycoside, such as D-glycopyranosyl azide 8, under the same conditions, provided for example the mixed Gal2-Glc triazine cluster 17 (Scheme 2). The efficient conjugation of unprotected glycosyl azides to trithiotriazine 2 thus provides

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

• , palmitoleic and oleic tails. However the mannose reactions of chains longer than C11 and oleic were unable to reach completion, which was attributed to the α-linkage of the azide at the anomeric centre, creating steric hindrance for the [3 + 2] cycloaddition. The yields for triple-chain amphiphiles are

Bis(β-lactosyl)-[60]fullerene as novel class of glycolipids useful for the detection and the decontamination of biological toxins of the Ricinus communis family

• Hirofumi Dohi,
• Takeru Kanazawa,
• Akihiro Saito,
• Keita Sato,
• Hirotaka Uzawa,
• Yasuo Seto and
• Yoshihiro Nishida

Beilstein J. Org. Chem. 2014, 10, 1504–1512, doi:10.3762/bjoc.10.155

• , Tsukuba, 305-8565, Japan 10.3762/bjoc.10.155 Abstract Glycosyl-[60]fullerenes were first used as decontaminants against ricin, a lactose recognition proteotoxin in the Ricinus communis family. A fullerene glycoconjugate carrying two lactose units was synthesized by a [3 + 2] cycloaddition reaction

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• by the use of a [3 + 2] cycloaddition reaction of an alkyne-bearing PEG reagent and an azide-functionalized tyrosine residue genetically incorporated on human superoxide dismutase-1 [30]. GlycoPEGylation, targeting carbohydrate sites, was conceived to produce a more homogeneous product with lower

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• reacts with azidobenzene 1a affording intermediate 6 by a [3 + 2] cycloaddition reaction. The intermediate 6 yields 4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde intermediate 7 after protonolysis of the C–Cu bond. This intermediate reacts with 1,2-diaminobenzene (3a) under the formation of the

Visible-light photoredox catalyzed synthesis of pyrroloisoquinolines via organocatalytic oxidation/[3 + 2] cycloaddition/oxidative aromatization reaction cascade with Rose Bengal

• Carlos Vila,
• Jonathan Lau and
• Magnus Rueping

Beilstein J. Org. Chem. 2014, 10, 1233–1238, doi:10.3762/bjoc.10.122

• Carlos Vila Jonathan Lau Magnus Rueping Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D-52074 Aachen, Germany 10.3762/bjoc.10.122 Abstract Pyrrolo[2,1-a]isoquinoline alkaloids have been prepared via a visible light photoredox catalyzed oxidation/[3 + 2] cycloaddition

• /oxidative aromatization cascade using Rose Bengal as an organo-photocatalyst. A variety of pyrroloisoquinolines have been obtained in good yields under mild and metal-free reaction conditions. Keywords: alkaloids; [3 + 2] cycloaddition; organocatalysis; oxidation; photochemistry; photoredox catalysis; Rose

• organic synthesis [10][11][12][13][14][15][16][17][18][19][20]. For example, dipolar [3 + 2] cycloaddition using azomethine ylides [21] is a powerful class of reactions that permits the synthesis of structural complex molecules in a straightforward way and has been used for the efficient synthesis of this

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• unit. Representative synthetic reactions of fullerene C60 (2) include cyclopropanation [29][30], [3 + 2] cycloaddition [31][32], [4 + 2] cycloaddition [33], nucleophilic addition [34], and radical addition reactions [35]. Two of the earliest and most widely used reactions, the Bingel–Hirsch reaction

• [29][30] and the Prato reaction [31][32] are illustrated in Scheme 1. The Bingel–Hirsch reaction affords a cyclopropanated fullerene 7, and the Prato reaction gives a [3 + 2] cycloaddition adduct 8. Concurrent with the development of covalent functionalization, numerous noncovalent functionalization

• the great electrophilicity of circumtrindene in the Bingel–Hirsch reaction, it came as no surprise that circumtrindene can act as a good dipolarophile in a [3 + 2] cycloaddition reaction as well. Accordingly, the azomethine ylide 23 generated in situ from N-methylglycine and formaldehyde adds to

Copper–phenanthroline catalysts for regioselective synthesis of pyrrolo[3′,4′:3,4]pyrrolo[1,2-a]furoquinolines/phenanthrolines and of pyrrolo[1,2-a]phenanthrolines under mild conditions

• Rupankar Paira,
• Tarique Anwar,
• Maitreyee Banerjee,
• Yogesh P. Bharitkar,
• Shyamal Mondal,
• Sandip Kundu,
• Abhijit Hazra,
• Prakas R. Maulik and
• Nirup B. Mondal

Beilstein J. Org. Chem. 2014, 10, 692–700, doi:10.3762/bjoc.10.62

• cycloaddition is presented in Scheme 3. The base (DBU) abstracts the acidic proton of furo[3,2-h]quinolinium 9a to generate the 1,3-dipole I. The Cu(II)–phenanthroline system activates the maleimide dipolarophile via coordination with the carbonyl group to undergo a [3 + 2] cycloaddition with the 1,3-dipole to

• synthesized (Scheme 5) from phenanthroline (11) and 2′-bromoacetophenones 8a and 8d, under basic alumina/microwave (180 W) conditions. These were then subjected to the optimized [3 + 2] cycloaddition protocol with different N-phenylmaleimide dipolarophiles 4a–c, which eventually produced similar cycloadducts

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

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• transformation, i.e., [3 + 2] cycloaddition (Scheme 9). Another application of an A3-MCR for the improvement of molecular complexity was published by Kokezu and Srinivas [39]. The authors suggested a straightforward AuBr3-catalyzed route to 2-, 3-, or 5-propargylamine substituted indoles 9. The reactions were

• reaction involving nitriles 52 as pro-nucleophiles (Scheme 28) [71]. Wu and co-workers successfully employed the isoquinolinium-2-ylamides 43 as an ylidic species in two-component tandem [3 + 2]-cycloaddition reactions with a series of substrates including dimethyl acetylenedicarboxylate [72

• isoquinolinium-2-ylamide 43 undergoes a [3 + 2]-cycloaddition reaction with carbodiimide 54. Further intramolecular rearrangement yields the desired 1-(isoquinolin-1-yl)guanidine 55. Moreover, isoquinolinium-2-ylamides 43 can participate as 1,3-dipoles in [3 + 2]-cycloaddition reactions with in situ generated

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• compounds. Preliminary experiments, however, showed that under standard conditions, a cycloaddition of diazodimedone and dimethyl diazomalonate with thiobenzophenone did not occur [5][6]. On the other hand, recent studies showed that the [3 + 2]-cycloaddition of this thioketone with many diazodicarbonyl

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• carbolactonization of terminal alkenes with arylboronic acids. Synthesis of tricyclic indolines via gold-catalyzed formal [3 + 2] cycloaddition. Gold(I) catalyzed aminoarylation of terminal alkenes in presence of Selectfluor [dppm = bis(diphenylphosphino)methane]. Mechanistic investigation on the aminoarylation of

Synthesis and characterization of novel bioactive 1,2,4-oxadiazole natural product analogs bearing the N-phenylmaleimide and N-phenylsuccinimide moieties

• Catalin V. Maftei,
• Elena Fodor,
• Peter G. Jones,
• M. Heiko Franz,
• Gerhard Kelter,
• Heiner Fiebig and
• Ion Neda

Beilstein J. Org. Chem. 2013, 9, 2202–2215, doi:10.3762/bjoc.9.259

• catalyzed [3 + 2] cycloaddition reaction. Unfortunately, the yield for this reaction was very low (<20%). In order to obtain compound 1 by the 1,3 dipolar cycloaddition route we changed the protocol. We synthesized the nitro derivative 2 (3-tert-butyl-5-(4-nitrophenyl)-1,2,4-oxadiazole) in situ by using the

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• with thermal formation of 2H-azirines. Photochemically, the ring of the 2H-azirines was opened to yield the nitrile ylides, which underwent a [3 + 2]-cycloaddition with 1,3-dipolarophiles. When diisopropyl azodicarboxylate serves as the dipolarophile, 1,3,4-triazoles become directly accessible starting

Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

• Leandro Lara de Carvalho,
• Robert Alan Burrow and
• Vera Lúcia Patrocinio Pereira

Beilstein J. Org. Chem. 2013, 9, 838–845, doi:10.3762/bjoc.9.96

• -diamines [19]. Herein, we report the reactivity and diastereoselectivity of 5a–c as heterodienes in a multicomponent [4 + 2]/[3 + 2] cycloaddition with ethyl vinyl ether (EVE) and selected electron-deficient alkenes in the presence of LiCl or LiClO4 as promoters. A study on the solvent effect was also

• route led to the obtainment of a great number of new chiral aminated nitroso acetals (7, 9–13) and the feasible synthesis of the pyrrolizidin-3-one scaffold. The good reactivity and diastereoselectivity of the new chiral-γ-aminated nitroalkenes 5a–c in multicomponent [4 + 2]/[3 + 2] cycloaddition

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• the other hand, the azide anion reacted with 2a, in acetonitrile, via a [3 + 2]-cycloaddition in which HNO2 was lost, providing the corresponding 1,2,3-triazole derivative. Direct reduction of 1,3-nitroamine derivatives 9a,b produced the corresponding 1,3-diamines in good yields. Keywords: amino

• -derivatives 10b,c (Table 1, entries 11 and 12) or the triazole derivative 11a (Table 1, entry 13) when THF or CH3CN were used as solvents, respectively. The formation of chiral 1,2,3-triazole derivative 11a was proposed to be by way of a [3 + 2]-cycloaddition with the azide group acting as 1,3-dipolarophile

One-pot tandem cyclization of enantiopure asymmetric cis-2,5-disubstituted pyrrolidines: Facile access to chiral 10-heteroazatriquinanes

• Ping-An Wang,
• Sheng-Yong Zhang and
• Henri B. Kagan

Beilstein J. Org. Chem. 2013, 9, 265–269, doi:10.3762/bjoc.9.32

• (Figure 5), and they have investigated their catalytic activities in asymmetric alkylation reactions for producing enantiomerically enriched amino acids. The synthesis of these quaternary ammonium ions follows a diversity-oriented approach wherein the tandem inter-[4 + 2]/intra-[3 + 2] cycloaddition of