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

• –alkyne cycloadditions, no traces of 1,5-regioisomers were observed [47][48]. The structure of the obtained compounds was assessed according to 1H NMR, 13C NMR and MS data. In particular, the 1H NMR spectra of 5-methyl-1-[(3RS,5SR)-2-methyl-3-(1H-1,2,3-triazol-1-ylmethyl)isoxazolidin-5-yl]pyrimidine-2,4

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

• is an effective photocatalyst in oxidatively induced photoredox transformations where less strongly oxidizing complexes (e.g., 1) are not successful. For instance, we have reported that 2 is uniquely capable of promoting radical cation mediated Diels–Alder cycloadditions [12], radical thiol–ene

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

• 14 failed. These results suggest that the reaction between C2F5CHN2 and alkynes belongs to type I of [3 + 2] cycloadditions [49]: It is accelerated by the alkyne`s EWGs and decelerated by EDGs. Next diverse disubstituted alkynes 15–22 (Table 3) with at least one strong EWG (–CO2Alk or –COAlk) were

• C2F5CHN2 vs CF3CHN2 To compare the reactivities of C2F5CHN2 and CF3CHN2 in [3 + 2] cycloadditions with alkynes, one must take into account two factors: steric and electronic [49]. On one hand, the C2F5 substituent is bulkier than the CF3 one, decreasing thereby the reactivity of C2F5CHN2 compared with

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• known to have a much lower toxic potential compared to CD monomers [20]. Native β-CD was already conjugated by esterification [21], reductive amination [22][23][24][25], amide coupling [26][27] and [2 + 3] cycloadditions [28] to both biogenic and synthetic polymers. Conjugation of CDs to polysaccharides

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• including azide–alkyne cycloadditions [9][10], Diels–Alder reactions [11][12], maleimide–thiol reactions [13], thiol–ene additions [14], and imine/oxime conjugations [15]. In this article we demonstrate that dihalocarbenes can be used to generate dihalocyclopropanes on olefin terminated SAMs. We recently

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• , recent efforts in electrochemical heterocycle synthesis can mostly be differentiated into anodic olefin coupling (section 1.1), radical cyclization (section 1.2), and trapping of anodically generated iminium/alkoxycarbenium ions (section 1.3). On the other hand, cycloadditions (section 2.1), sequential

• solution and dichloromethane is employed as electrolyte. The method features attractive yields (70–95%) and a broad scope with regard to substitution on the phenylene moiety (R1 and R2) and on the oxazole unit (R3). 2 Intermolecular cyclizations 2.1 Cycloadditions with anodically generated intermediates A

• well-established strategy for the construction of certain six-membered heterocycles is the electrochemical generation of heterodienes for Diels–Alder cycloadditions [65][66]. In this context, electrosynthesis provides a significant advantage over conventional methods: Instable diene precursors which

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• ] cycloadditions of azido-ketenimines and azido-carbodiimides (Scheme 1) [29]. The available starting materials for the synthesis of these compounds, however, are limited. Very recently, Perumal [30] reported an efficient method for the synthesis of indolo[1,2-a]quinazoline through a Cu(I)-catalyzed intramolecular

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• . Keywords: 1,3-dipolar cycloadditions; multicomponent; one-pot three-component reactions; pyrrolo[1,2-a]benzimidazole; pyrrolo[1,2-a]quinoxalin-4-one; Introduction The pyrrolo[1,2-a]quinoxaline system has significant biological activities and is a subject fo constant interest. This skeleton is a

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• ][23][24][25]. There are examples of oxazole photochemical intermolecular cycloadditions [26][27][28][29][30][31][32], but to the best of our knowledge, there are no examples of intramolecular photocycloaddition. We describe herein, the synthesis of new 4- and 5-(2-vinylstyryl)oxazoles (1, 2) and their

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• synthesized a series of ferrocene-modified planar chiral phosphines featuring a new skeleton (Figure 3) [44][45]. Among these compounds, the P-cyclohexyl phosphine C1 proved to be the most efficient catalyst for [3 + 2] cycloadditions of ethyl 2,3-butadienoate with activated enones, fumarate esters, and

• methylenebenzofuranone derivatives, constructing a variety of complex polysubstituted spirocyclopentenebenzofuranones in high yields with good to excellent enantioselectivities [75]. Using the amino acid-derived chiral phosphine H2, Lu and co-workers explored asymmetric [3 + 2] cycloadditions between MBH carbonates and

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• the synthesis of triazole-substituted titanocenes via strain-driven 1,3-dipolar cycloadditions between azide-functionalized titanocenes and cyclooctyne has been developed. It features the first synthesis of titanocenes containing azide groups. These compounds constitute ‘second-generation

• active complexes allows the identification of structural features essential for biological activity. Keywords: azides; click-chemistry; cycloadditions; cytotoxicity; titanocenes; Introduction Group 4 metallocenes and derivatives of Cp2TiCl2, in particular, continue to be in the focus of contemporary

• nucleophiles. We decided to address these issues by employing cationic amide-substituted titanocenes as building blocks and strain-driven 1,3-dipolar cycloadditions [34][35][36][37][38][39][40] as synthetic methodology for the preparation of such ‘second-generation’ functional titanocenes. This line of action

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

• with different valency and alkyl spacer lengths by means of Cu(I)-catalysed azide–alkyne cycloadditions. Evaluation of these compounds as α-mannosidase inhibitors led to significant multivalent effects and further demonstrated the decisive influence of scaffold rigidity on binding affinity enhancements

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• -terminated SAMs [33], by Diels–Alder reaction of cyclopentadienes and furans on maleimide-terminated SAMs [34], by thiol–ene click reaction of functionalized thiols on alkene-terminated SAMs [35] as well as by strain promoted cycloadditions on azide- and nitriloxide-terminated SAMs [36] using μCP. Homogenous

Cyclization–endoperoxidation cascade reactions of dienes mediated by a pyrylium photoredox catalyst

• Nathan J. Gesmundo and
• David A. Nicewicz

Beilstein J. Org. Chem. 2014, 10, 1272–1281, doi:10.3762/bjoc.10.128

• challenges. Classical approaches to the introduction of cyclic peroxides typically rely on cycloadditions of alkenes and dienes with singlet oxygen. However, ene processes can often compete, leading to complex mixtures of hydroperoxide adducts [1][6][7][8]. More recently, cyclization reactions of

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

• side electronically more favorable for a nucleophilic attack. Prato reaction Cycloadditions to the π-system constitute another major family of fullerene reactions. In particular, 1,3-dipolar reagents readily add to the 6:6-bond of fullerene C60, which acts as a good dipolarophile. Among such [3 + 2

• ] cycloadditions, the reaction with azomethine ylides has found great popularity, because it leads to versatile pyrrolidine derivatives of C60. The sources of the ylide can be iminium salts, aziridines, oxazolidines or silylated iminium compounds. In 1993, Prato and coworkers developed the protocol that is now

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• electron spin traps [1] and in cycloaddition reactions [2]. As nitrones undergo 1,3-dipolar cycloadditions under mild conditions with a variety of unsaturated substances with a catalyst [3][4] or without a catalyst [5] they are important for the synthetic accessibility of five-membered heterocycles

• isoxazolidines 5a/b (Scheme 3). From the NMR spectra it could be determined that only the 5-substituted isoxazolidine was formed with a ratio of 60/40 of Z/E. Although 1,3-dipolar cycloadditions of nitrones with alkenes are controlled by molecular orbital interactions, the steric character of the molecular

• . 1,3-dipolar cycloadditions of model nitrones with dimethyl itaconate confirmed the proposed mechanism of cross-linking. Experimental Materials Acryloyl chloride (97%), crotonic acid (98%), itaconic acid (IA, 97%), methyl acrylate (99%), methyl crotonate (98%), succinic acid (SA, 99%), p

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• isoindolo[2,1-a]quinolone derivatives involves N-acyliminium ions or appropriate electron-deficient Schiff bases and subsequent [4 + 2] inverse-demand hetero-Diels–Alder cycloadditions with alkenes [11][12][13][14][15][16][17]. Vinylic systems from isoeugenol [11], cyclopentadiene [12], enones [13], vinyl

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

• betaines by inter- or intramolecular cycloadditions are typical reactions [18][19]. To prove the initial formation of an N-heterocyclic carbene in this reaction we tried trapping reactions starting from 12a and 12e with carbonylbis(triphenylphosphine)rhodium(I) chloride under otherwise unchanged reaction

Domino reactions of 2H-azirines with acylketenes from furan-2,3-diones: Competition between the formation of ortho-fused and bridged heterocyclic systems

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Viktoriia V. Pakalnis,
• Roman O. Iakovenko and
• Dmitry S. Yufit

Beilstein J. Org. Chem. 2014, 10, 784–793, doi:10.3762/bjoc.10.74

• ]. In particular, unsubstituted acylketenes, the reactivity of which towards azirines is until now unknown, cannot be generated from diazo compounds. An alternative source of acylketenes can be furan-2,3-diones, which have been used in reactions with nucleophiles and various cycloadditions [30][31][32

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

• subsequent transformations [19][22][26]. Examples of IMCR orthogonal species or functionalities are alkenes, alkynes and azides which may give the cyclic analogues via subsequent ring closing metathesis (RCM) or 1,3-dipolar cycloadditions. In contrast, protected functional groups first require a deprotection

Preparation of new alkyne-modified ansamitocins by mutasynthesis

• Kirsten Harmrolfs,
• Lena Mancuso,
• Binia Drung,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2014, 10, 535–543, doi:10.3762/bjoc.10.49

• cycloadditions better known as “copper mediated Click-chemistry” while alkenes, especially vinyl- and allylbenzoic systems, are predestined for being utilized in cross metathesis reactions. Therefore a series of aminobenzoic acids 9–20 (Figure 1) were prepared (see Supporting Information File 1). We expected

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

• -type reactions, hetero Diels–Alder reactions, 1,3-dipolar cycloadditions and nitroso aldol reactions [93]. The process was firstly accomplished with preformed aryl-substituted aldimines [94] and then developed as a MCR for less stable alkyl-substituted aldimines, which were prepared in situ from

Additive-assisted regioselective 1,3-dipolar cycloaddition of azomethine ylides with benzylideneacetone

• Chuqin Peng,
• Jiwei Ren,
• Jun-An Xiao,
• Honggang Zhang,
• Hua Yang and
• Yiming Luo

Beilstein J. Org. Chem. 2014, 10, 352–360, doi:10.3762/bjoc.10.33

• Chuqin Peng Jiwei Ren Jun-An Xiao Honggang Zhang Hua Yang Yiming Luo School of Chemistry and Chemical Engineering, Central South University,Changsha, Hunan 410083, P. R. China 10.3762/bjoc.10.33 Abstract 1,3-Dipolar cycloadditions of isatins, benzylamine and benzylideneacetones were studied to

• employed as starting materials to conduct 1,3-dipolar cycloadditions to yield spirooxindole core structures [16][17][18][19][20]. Owing to the ease of preparation, the azomethine ylides generated from isatin with α-amino acids or amines were frequently chosen as important 1,3-dipolar intermediates to react

• -constructed pyrrolidine. However, unsaturated ketones with α-hydrogens such as benzylideneacetone, which have attracted great interest due to their synthetic potential [40][41][42], have not been exhaustively studied as suitable dipolarophiles for 1,3-dipolar cycloadditions of azomethine ylides to prepare

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• studies on the synthesis of 2-boron-substituted 1,3-dienes and their reactivity in tandem reactions, concentrating mainly upon [4 + 2]-cycloadditions followed by cross-coupling reactions. Potassium and tetra-n-butylammonium buta-1,3-dienyl-2-trifluoroborates 15 were synthesized in good yields from

• /palladium cross-coupling sequences of a 2-diethanolaminoboron-substituted 1,3-diene 16 were investigated [52]. This diene has proved to be significantly more reactive and more regioselective in [4 + 2]-cycloadditions compared to the corresponding trifluoroborate. The cycloadducts were then efficiently cross

• ]-cycloadditons, can further be engaged in an allylation reaction that significantly increased the structural diversity of the final products (Scheme 24). As 3-boronoacrolein esters which have been used in metal-catalyzed inverse electron demand [4 + 2]-cycloadditions, 32 reacted with ethyl vinyl ether in the

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• reduction of the carbonyl group [43] and TBS cleavage, propargylic ether 18 was obtained (88% yield over two steps) [44]. The alkyne moiety provides options for further transformations, e.g. Sonogashira reactions, Glaser couplings or 1,3-dipolar cycloadditions (click reactions) [45]. We were also interested