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

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

• -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

• 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

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

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

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

• quinoxalines [6] have been recently reviewed. Among other synthetic routes, the 1,3-dipolar cycloaddition of heterocyclic N-ylides with various activated alkynes or alkenes is an important method for constructing fused heterocyclic systems such as pyrrolo[1,2-a]quinoxaline and pyrrolo[1,2-a]benzimidazole [7][8

• cycloadducts 8. In order to explain the above mentioned results, we investigated the influence of reaction conditions on the ratio of the final reaction products 4 and 5 in 1,3-dipolar cycloaddition reactions of the 1-benzyl-3-(ethoxycarbonylmethyl)benzimidazolium bromide 6 (R = H, R1 = benzyl) with ethyl

• demonstrated that 1,3-dipolar cycloaddition reactions of 1-benzyl-3-(alkoxycarbonylmethyl)benzimidazolium ylides with activated alkynes led to a mixture of pyrrolo[1,2-a]quinoxalin-4-ones and pyrrolo[1,2-a]benzimidazoles. Pyrrolo[1,2-a]quinoxalin-4-ones are always the major reaction product and the ratio of

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

• annulation of N’-(2-alkynylbenzylidene)hydrazides followed by an 1,3-dipolar cycloaddition. Results and Discussion Based on Wu’s work on the silver triflate-catalyzed tandem reaction of N’-(2-alkynylbenzylidene)hydrazides with dimethyl acetylenedicarboxylate [28], we started our research by examining the

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

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

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• '-UUGCA-5', has been prepared on a precipitative tetrapodal tetrakis(4-azidomethylphenyl)pentaerythritol support. The 3'-terminal nucleoside was coupled to the support as a 3'-O-(4-pentynoyl) derivative by Cu(I) promoted 1,3-dipolar cycloaddition. Couplings were carried out with 1.5 equiv of the building

• reported [16] pentaerythritol-derived tetraazido support 7 was used to assemble a pentameric oligoribonucleotide, 5'-UUGCA-3', from the building blocks described above. The 3'-terminal block 6a was first attached to the support by Cu(I) promoted 1,3-dipolar cycloaddition [25][26] (Scheme 2). The procedure

End group functionalization of poly(ethylene glycol) with phenolphthalein: towards star-shaped polymers based on supramolecular interactions

• Carolin Fleischmann,
• Hendrik Wöhlk and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 2263–2269, doi:10.3762/bjoc.10.235

• and Discussion We herein describe the synthesis of the host and guest compound, which were further utilized for the preparation of star shaped polymers based on supramolecular interactions. The preparation of both, the host and the guest compound, occurred via 1,3-dipolar cycloaddition, in which the

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• these compounds (17, 18 and 19) was prepared in our laboratories by a combination of Diels–Alder cycloaddition and 1,3-dipolar cycloaddition reactions [21]. We found that the Raney nickel-mediated cleavage took place readily on 17 to yield a β-hydroxyketo-functionalized 7-oxanorbornane 20 (Scheme 3

Multicomponent reactions in nucleoside chemistry

• Mariola Koszytkowska-Stawińska and
• Włodzimierz Buchowicz

Beilstein J. Org. Chem. 2014, 10, 1706–1732, doi:10.3762/bjoc.10.179

• polyoxin C hydrochloride 105*HCl (Scheme 44) [121]. The reaction cascade involved thermal formation of the corresponding azomethine ylide from substrate 105*HCl and benzaldehyde, followed by 1,3-dipolar cycloaddition of the ylide to N-methylmaleimide. The formation of compound 107 as the only product was

Clicked and long spaced galactosyl- and lactosylcalix[4]arenes: new multivalent galectin-3 ligands

• Silvia Bernardi,
• Paola Fezzardi,
• Gabriele Rispoli,
• Stefania E. Sestito,
• Francesco Peri,
• Francesco Sansone and
• Alessandro Casnati

Beilstein J. Org. Chem. 2014, 10, 1672–1680, doi:10.3762/bjoc.10.175

• glycocalixarenes “Click Chemistry” [23] reactions are extensively used to conjugate (oligo)saccharides to macrocyclic structures due to the mild conditions and the high yields [24]. For the synthesis of glycocalixarenes the amino–isothiocyanate condensation [25][26][27][28][29][30] or the 1,3-dipolar cycloaddition

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

• molecules. Since no metal complexes are required to catalyze the 1,3-dipolar cycloaddition [41][42][43], the reaction can be even used for the functionalization of biomolecules in living systems and has therefore been called bioorthogonal [34][35]. To the best of our knowledge, no examples of the Ti

• cycloaddition with an alkyne-functionalized titanocene has been described [44]. Therefore, the properties of triazol-substituted titanocenes, the products of the 1,3-dipolar cycloaddition, are also largely unexplored. Results and Discussion Synthesis of the titanocenes Preparation of the starting materials We

• functionalization through the strain-driven 1,3-dipolar cycloaddition with cyclooctyne. The original conditions of Wittig [36], the reaction of cyclooctyne with phenyl azide, and the numerous applications pioneered by Bertozzi suggest that the reaction proceeds under mild conditions [34][35][37][38][39][40

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

• others, free radical polymerization of C-6 of the glucosamine residues with poly(ethylenglycol) acrylate [58]; free-radical polymerization of C-1 of glucosamine with mPEG [59] and 1,3-dipolar cycloaddition between the azide of an N-azidated chitosan and mPEG derivatives containing a triazolyl moiety [60

A complete series of 6-deoxy-monosubstituted tetraalkylammonium derivatives of α-, β-, and γ-cyclodextrin with 1, 2, and 3 permanent positive charges

• Martin Popr,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2014, 10, 1390–1396, doi:10.3762/bjoc.10.142

• Huisgen 1,3-dipolar cycloaddition [30] (most popular ‘click reaction’) or the reduction to the amine. Our strategy involved the synthesis of the alkylation agent 1-azido-2-iodoethane (24) (Scheme 5) which would be used for the quaternization of the tertiary amine intermediate. The reaction sequence for

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• groups onto polymers via convenient ‘click’ reaction with organic azido molecules without PLA backbone degradation [17]. ‘Click’ chemistry [20], which is copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and alkynes, has been developed and utilized in recent years as a powerful synthetic strategy