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

• 4i), respectively. The regio- and stereospecificity and the apparent reaction rate increase by the introduction of electron-withdrawing substituents into the benzonitrile oxide structure, allow to presume that the reaction of enamines with nitrile oxides can be described as 1,3-dipolar cycloadditions

• 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

Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

• Grzegorz Mlostoń,
• Róża Hamera-Fałdyga,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 1421–1427, doi:10.3762/bjoc.12.136

• [3 + 2]-cycloadditions. The high reactivity of ferrocenyl thioketones is demonstrated by the fact that no products of competitive reactions, such as dimerization of the intermediate 1,3-dipole or 1,3-dipolar electrocyclizations, were observed. Based on these observations one can expect that

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

Synergistic chiral iminium and palladium catalysis: Highly regio- and enantioselective [3 + 2] annulation reaction of 2-vinylcyclopropanes with enals

• Haipan Zhu,
• Peile Du,
• Jianjun Li,
• Ziyang Liao,
• Guohua Liu,
• Hao Li and
• Wei Wang

Beilstein J. Org. Chem. 2016, 12, 1340–1347, doi:10.3762/bjoc.12.127

• ; Introduction The power of “donor–acceptor” (D–A) cyclopropanes as versatile 1,3-dipolar components is fuelled by its capacity of serving a complementary approach to a wide array of 5-membered ring structures, which are difficult or impossible to access by classic [3 + 2] cycloaddition reactions [1][2][3][4][5

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

• : 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

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

• . 6 1,3-Dipolar cycloaddition-based multicomponent reactions 1,3-Dipolar cycloaddition-based multicomponent reactions usually involve the cycloaddition of in situ generated 1,3-dipoles and dipolarophiles to give five-membered heterocycles. In recent years, many heterocyclic phosphonates have been

• developed for the preparation of different 3-carbo-5-phosphonylpyrazoles 223 (Scheme 45) [83]. The corresponding phosphonylpyrazoles 223 were formed via a Claisen–Schmidt/1,3-dipolar cycloaddition/oxidation process under basic conditions in MeOH in 30–91% yields. The dual reactivity of diethyl (1-diazo-2

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• important classes of organic reactions, and [3 + 2]- cycloadditions, also known as 1,3-dipolar cycloadditions or Huisgen reactions, offer a universal tool for the preparation of five-membered heterocycles with a variable number of heteroatoms in the ring [1][2]. In addition to their practical importance

• . Only after warming up above −45/40 °C compounds 2 are expected to decompose yielding the reactive thiocarbonyl ylide 3. Under these conditions, the latter intermediates can undergo either 1,3-dipolar electrocyclization to give thiiranes 8 or dimerization leading to 1,4-dithianes 4 [20][26]. This

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• drug delivery systems and toxic compounds scavengers, and have been obtained by grafting CDs into polymeric matrices. A multi-carrier for combined diagnostic and theranostic applications was obtained via the functionalization of carbon nanotubes with CD using a MW-assisted 1,3-dipolar cycloaddition. As

Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation

• Jochen Kraft,
• Martin Golkowski and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 166–171, doi:10.3762/bjoc.12.18

• stereo-differentiating potential of carbohydrate ligands in this type of reaction where their gluco-PHOX ligand, derived from glucosamine, resulted in a high enantiomeric excess of up to 98% [14]. Recently, Vidal et al. reported on a spiro-bis(isooxazoline) ligand A (Figure 1) [15] prepared via 1,3

• -dipolar cycloaddition of 2,6-pyridinedicarbonitrile N,N-dioxide to acetyl protected exo-glucal. The performance of ligand A in asymmetric catalysis was then tested in the palladium-catalyzed allylic addition of dimethyl malonate to 1,3-diphenylallyl acetate which, however, afforded the desired allylic

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• -like macrocycle on the other side, have been easily linked by microwave azide–alkyne 1,3-dipolar cycloaddition. The preliminary relaxivity study of these heterobimetallic complexes was also investigated for potential MRI applications. Results and Discussion We first wish to report a “library” of azido

Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks

• Amit M. Jabgunde,
• Alejandro Gimenez Molina,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171

• -triazol-1-ylmethylphenyl}pentaerythritol support (3) is outlined in Scheme 1. Commercially available S-propargyl thioacetate was first conjugated to the tetrakis-O-[4-(azidomethylphenyl)pentaerythritol support (1) [7] by Cu(I) catalyzed 1,3-dipolar cycloaddition [24][25], yielding tetrakis-O-({4-[4

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

• )-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of copper(II) 2-azido-5,10,15,20-tetraphenylporphyrin or zinc(II) 2-azidomethyl-5,10,15,20-tetraphenylporphyrin with various alkyne derivatives of xanthones in DMF containing CuSO4 and ascorbic acid at 80 °C. Furthermore, these metalloporphyrins underwent

• fluorescence spectra of these porphyrin–xanthone dyads. Keywords: 1,3-dipolar cycloaddition; fluorescence; synthesis; triazoloporphyrin-xanthone dyads; UV–vis spectroscopy; Introduction In the past few decades, porphyrin macrocycles have emerged as a unique class of heterocyclic compounds and as most

• porphyrins with diverse functionalities such as quinolone [19], ferrocene [20], carbohydrate [21] and fullerene [22] through a copper(I)-catalyzed Huisgen–Sharpless–Meldal 1,3-dipolar cycloaddition reaction [23][24]. Some of these triazolo-bridged porphyrin dyads have shown an efficient intramolecular energy

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

Indolizines and pyrrolo[1,2-c]pyrimidines decorated with a pyrimidine and a pyridine unit respectively

• Marcel Mirel Popa,
• Emilian Georgescu,
• Mino R. Caira,
• Florentina Georgescu,
• Constantin Draghici,
• Raluca Stan,
• Calin Deleanu and
• Florea Dumitrascu

Beilstein J. Org. Chem. 2015, 11, 1079–1088, doi:10.3762/bjoc.11.121

• Fundulea, Calarasi, Romania 10.3762/bjoc.11.121 Abstract The three possible structural isomers of 4-(pyridyl)pyrimidine were employed for the synthesis of new pyrrolo[1,2-c]pyrimidines and new indolizines, by 1,3-dipolar cycloaddition reaction of their corresponding N-ylides generated in situ from their

• pyrimidine. Herein, we report the efficient synthesis of small libraries of structurally diverse pyrrolo-fused heterocycles starting from the 4-pyridylpyrimidine isomers via 1,3-dipolar cycloaddition of corresponding N-ylides with several activated alkynes. The biologic and luminescent properties of newly

• ]pyrimidines or pyrimidinyl-substituted indolizines. The synthetic strategy was the 1,3-dipolar cycloaddition reaction of the corresponding N-ylides [21][22][23][24][25]. The structural variety of the compounds was determined by the series of dipolarophiles employed. The new final compounds were structurally

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• support in asymmetric organocatalysis. The use of chiral imidazolidinones in organocatalysis has been extensively reported for a wide range of enantioselective reactions involving α,β-unsaturated aldehydes, such as the Diels–Alder reactions [50], 1,3-dipolar cycloadditions [51] and Friedel–Crafts

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• 1,3-dipolar cycloaddition and reduction [34] (Figure 3). (−)-Tashiromine has been accessed through the ring closure of difunctionalized acyclic chiral sulfonamide-based β-amino acids [35], the cyclization of pyrrole derivatives with a chiral side-chain [36], or the enantioselective arylation of

On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation

• Andrey S. Mereshchenko,
• Alexey V. Ivanov,
• Viktor I. Baranovskii,
• Grzegorz Mloston,
• Ludmila L. Rodina and
• Valerij A. Nikolaev

Beilstein J. Org. Chem. 2015, 11, 504–513, doi:10.3762/bjoc.11.57

• , Poland 10.3762/bjoc.11.57 Abstract The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC) and thioketones preferably occurs with Z,E-conformers and leads to the formation of transient thiocarbonyl ylides in two stages. The thermodynamically favorable further transformation of C

• , carbocyclic diazodiketones are much less reactive under similar conditions due to the locked cyclic structure and are unfavorable for the 1,3-dipolar cycloaddition due to the Z,Z-conformation of the diazo molecule. This structure results in high, positive values of the Gibbs free energy change for the first

• stage of the cycloaddition process. Keywords: diazocarbonyl compounds; 1,3-dipolar cycloaddition; 1,3-oxathioles; thiiranes; thiocarbonyl ylides; thioketones; Introduction Dipolar cycloadditions of diazo compounds have been of great interest for a long time as they provide a means for the preparation

Functionalized branched EDOT-terthiophene copolymer films by electropolymerization and post-polymerization “click”-reactions

• Miriam Goll,
• Adrian Ruff,
• Erna Muks,
• Felix Goerigk,
• Beatrice Omiecienski,
• Ines Ruff,
• Rafael C. González-Cano,
• Juan T. Lopez Navarrete,
• M. Carmen Ruiz Delgado and
• Sabine Ludwigs

Beilstein J. Org. Chem. 2015, 11, 335–347, doi:10.3762/bjoc.11.39

• levels. The use of EDOT-N3 as co-monomer furthermore allows modifications of the films by polymer analogous reactions. Here, we exemplarily describe the post-functionalization with ionic moieties by 1,3-dipolar cycloaddition (“click”-chemistry) which allows to tune the surface polarity of the copolymer

• pyrrole was conducted [30]. Post-polymerization processes on the other hand have to provide high yields and mild reaction conditions to keep the formed polymer backbone intact and to reach a considerable degree of conversion of functional groups. The Cu(I)-mediated 1,3-dipolar cycloaddition between azides

• during the polymerization process. In a next step we further transferred the copolymerization approach to the azidomethyl-substituted EDOT-N3 monomer which allows for the straightforward modification with various alkynes by Cu(I)-catalyzed 1,3-dipolar cycloaddition (“click”-reaction) [57]. For the

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

• of 5.0–40 μM. The synthesized compounds do not show any antiviral activity. Keywords: antitumor activity; click chemistry; 1,3-dipolar cycloaddition; nucleic acids; 2’-oxa-3’-aza-4’a-carbanucleoside analogs; Introduction Synthetic modified nucleosides are of great interest as potential new lead

• 13 and 14 is described in Scheme 1 (and Table 1). (3′RS,5′SR)-2′-N-methyl-3′-hydroxymethyl-1′,2′-isoxazolidin-5′-ylthymine 8, obtained as the main compound, in a two-step process, by 1,3-dipolar cycloaddition of vinyl acetate to C-[(tert-butyldiphenylsilyl)oxy]-N-methylnitrone, followed by Hilbert

Novel biphenyl-substituted 1,2,4-oxadiazole ferroelectric liquid crystals: synthesis and characterization

• Mahabaleshwara Subrao,
• Dakshina Murthy Potukuchi,
• Girish Sharada Ramachandra,
• Poornima Bhagavath,
• Sangeetha G. Bhat and
• Srinivasulu Maddasani

Beilstein J. Org. Chem. 2015, 11, 233–241, doi:10.3762/bjoc.11.26

• The synthesis of 1,2,4-oxadiazoles involves [30] a single stage dehydration of O-acylated amidoximes via a reaction between amidoximes and derivatives of carbonyl compounds (esters, amides, acids, acid chlorides, aldehydes, etc.). Otherwise, the reaction is based on the 1,3-dipolar cycloaddition of N

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

• hydrogenation of the latter with Lindlar catalyst afforded 7 almost quantitatively. Likewise, copper(I)-catalyzed 1,3-dipolar cycloaddition (Click reaction) [15][16][17][18] of 5 with Fmoc-protected propargylamine afforded first t-butyl benzoate 8 in 87% yield. Hydrogenation of the latter with Pd on charcoal