Recent advances in metathesis-derived polymers containing transition metals in the side chain

• Ileana Dragutan,
• Valerian Dragutan,
• Bogdan C. Simionescu,
• Albert Demonceau and
• Helmut Fischer

Beilstein J. Org. Chem. 2015, 11, 2747–2762, doi:10.3762/bjoc.11.296

• triazolyl unit was first attached to the η4-cyclopentadiene CpCo(I) complex by click reaction of the corresponding alkyne precursor and then the triazolyl-Co scaffold was incorporated into the norbornene monomer 9 by conventional esterification. It is important to note that the cyclopentadienyl-cobalt-1,3

• and tetraethylene glycol groups. Synthesis of redox-robust triazolylbiferrocenyl polymers 4. Synthesis of cobaltocenium-containing polymers by ROMP. Cobaltocenium-appending copolymers by the ROMP approach (X = PF6, Y = BPh4 or Cl). Cobalt-containing polymers by click and ROMP approach. Synthesis of

Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

• Mohammed Salah Ayoup,
• David B. Cordes,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 2671–2676, doi:10.3762/bjoc.11.287

• illustrated in Scheme 4 [17]. Reduction of benzyl azide 21 to generate amine 27 as its hydrochloride salt was achieved by a Staudinger reduction in good yield [18]. Azide 21 was also amenable to a ‘click’ reaction, in this case with the acetylenic protected amino acid 24 [19]. This gave the 1,2,3-triazol

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• , Universidad de Sevilla, c/ Prof. García González 1, E-41012, Sevilla, Spain 10.3762/bjoc.11.282 Abstract The synthesis of new multivalent architectures based on a trihydroxypiperidine α-fucosidase inhibitor is reported herein. Tetravalent and nonavalent dendrimers were obtained by means of the click

• ). The low yield observed for the click reaction of the deprotected azido derivative 10 can be ascribed to the tricky purification of 11 that was recovered from silica gel only by eluting with 33% NH4OH due to its high basicity (see Experimental section). For this reason we decided to change the strategy

• by performing the click reaction on the protected azido derivative 4, analogously to what reported with the tetravalent scaffold 5. Reaction of 4 (9 equiv) with the nonavalent alkyne scaffold 6 gave compound 12 in excellent 92% yield (Scheme 5). After treatment in acidic methanol at room temperature

Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

• Zhan-Jiang Zheng,
• Ding Wang,
• Zheng Xu and
• Li-Wen Xu

Beilstein J. Org. Chem. 2015, 11, 2557–2576, doi:10.3762/bjoc.11.276

• Selective Oxidation, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, P. R. China 10.3762/bjoc.11.276 Abstract The Cu(I)-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles

• . Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC) for such transformations. In

• addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted. Keywords: bistriazoles; click chemistry; cycloaddition; homogeneous catalysis; oxidative

Copper catalysis in organic synthesis

• Sherry R. Chemler

Beilstein J. Org. Chem. 2015, 11, 2252–2253, doi:10.3762/bjoc.11.244

• . Some of the most highly cited papers of all time on this topic are reviews on conjugate addition, cross-coupling, and [3 + 2] “Click” reaction applied to bioconjugation. The growth in copper-catalyzed organic reactions may be driven by a couple of factors. First, copper chemistry is incredibly diverse

• field of copper-catalysis from 7 countries make up this Thematic Series, “Copper catalysis in organic synthesis”. Contributions include authoritative reviews on the latest developments in copper-catalyzed Click applications, C–N cross-coupling, C–H functionalization, trifluoromethylations, asymmetric

• synthesis, amide bond formation and photochemical Click reaction development. I am grateful to the contributors and the reviewers who participated in the production of this Thematic Series. It is clear from the impact copper catalysis has had on organic synthesis that copper should be considered a first

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

• Nicolas Desbois Sandrine Pacquelet Adrien Dubois Clement Michelin Claude P. Gros Université de Bourgogne Franche-Comté, ICMUB (UMR CNRS 6302), 9 Avenue Alain Savary, BP 47870, 21078 Dijon Cedex, France 10.3762/bjoc.11.239 Abstract The Cu(I)-catalysed Huisgen cycloaddition, known as “click

• are promising contrast agents (CA) in MRI. Keywords: click chemistry; corrole; DOTA; microwave; NOTA; porphyrin; Introduction Magnetic resonance imaging (MRI), positron emission tomography (PET) or single photon emission computed tomography (SPECT) are actually the most commonly used imaging

• and alkyne derivatives to further interconnect by microwave-assisted click reaction. Azidocorroles/porphyrins Azidocorrole 1 [9] was obtained by the condensation of the corresponding meso-mesityl-substituted dipyrromethane with 4-azidobenzaldehyde in the presence of a catalytic amount of

Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

• Redouane Beniazza,
• Natalia Bayo,
• Florian Molton,
• Carole Duboc,
• Stéphane Massip,
• Nathan McClenaghan,
• Dominique Lastécouères and
• Jean-Marc Vincent

Beilstein J. Org. Chem. 2015, 11, 1950–1959, doi:10.3762/bjoc.11.211

• , F-38000 Grenoble, France Univ. Bordeaux, IECB, UMS 3033/US 001, 2 rue Escarpit, 33607 Pessac, France CNRS, IECB, UMS 3033, 33600 Pessac, France INSERM, IECB, US 001, 33600 Pessac, France 10.3762/bjoc.11.211 Abstract The search for copper catalysts able to perform effectively click reactions in

• photoreduced in water when alkynes were present in solution. The catalytic activity of 1 for click reactions involving a range of water-soluble alkynes and azides, in particular saccharides, was tested under various illumination conditions. Complex 1 was found to exhibit a photolatent character, the

• photogenerated copper(I) being very reactive. On irradiating aqueous reaction mixtures containing 1 mol % of 1 at 365 nm (TLC lamp) for 1 h, click reactions were shown to proceed to full conversion. Keywords: benzophenone photosensitizer; bioconjugation; click chemistry; copper; photoreduction; Introduction

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

• ) were synthesized in good yields by the “click reaction” of 3,6-diethynylxanthen-9-one (11) with copper and zinc azidoporphyrins, respectively. Further, the free-base diporphyrins 12b and 13b were obtained in 81% and 84% yields, respectively after the treatment of 12a with conc. H2SO4 at 0 °C and 13a

• -diethynylxanthen-9-one. In addition, a new series of various β-triazole-linked porphyrin–xanthone conjugates and xanthone-bridged triazoloporphyrin dyads were synthesized through click chemistry in moderate to good yields. The preliminary photophysical evaluation of these π-conjugated molecules revealed a

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• -deprotection with azide–alkyne cycloaddition, producing hindered triazoles in 6 hours. This tandem reaction was optimal with a copper(II) triflate and sodium ascorbate (NaAsc) as a mild reductant. The outcome that copper(II) triflate provides the highest yields for the one-pot deprotection/click reaction was

• (blue). KA2 coupling followed by tandem silyl deprotection and triazole formation. Silyl deprotection/click conditions applied to tert-butylacetylene. An identical yield is observed without TBAF. High overall yield of 1,2,3-triazole fully-substituted at the 4-position. Optimization of silyl deprotection

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• ., after the "click" reaction) [61]. Conclusion In this work, we demonstrated the generality and the versatility of oxaphospholanes such as 4 and 5 to serve as precursors for the synthesis of γ-hydroxypropyl (±)-phosphinates and phosphine oxides, respectively, using Grignard reactions. Noteworthy is the

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

• 308 in the presence of CuSO4 and sodium ascorbate in acetonitrile/water to deliver the desired cyclophane derivative 309 (56%, Scheme 53). Similarly, a novel BINOL-based cyclophane 310 has been synthesized via click chemistry by incorporating two triazole moieties in the macrocycle [187]. Li and co

Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• literature and the data were compared with that reported [34]. The structure of the minor diastereomer (±)-4’ was assigned based on 2D NMR correlations. Secondly, the azido alcohol (±)-3 was subjected to a click reaction with phenylacetylene under standard conditions and the resulting two compounds, (±)-5

Quarternization of 3-azido-1-propyne oligomers obtained by copper(I)-catalyzed azide–alkyne cycloaddition polymerization

• Shun Nakano,
• Akihito Hashidzume and
• Takahiro Sato

Beilstein J. Org. Chem. 2015, 11, 1037–1042, doi:10.3762/bjoc.11.116

• alkynes with a copper(I) catalyst under mild conditions even in the presence of various functional groups [1][2][3]. CuAAC is thus the most important reaction in “click chemistry” [4][5][6][7]. A number of studies have been published on CuAAC, which is applied in a wide range of fields from bio-related

Carboxylated dithiafulvenes and tetrathiafulvalene vinylogues: synthesis, electronic properties, and complexation with zinc ions

• Yunfei Wang and
• Yuming Zhao

Beilstein J. Org. Chem. 2015, 11, 957–965, doi:10.3762/bjoc.11.107

• and Cu-catalysed alkyne–azide cycloaddition (i.e., click) reactions [22][23][24][25][26]. In this work, we continued to explore the class of carboxylated diphenyl-TTFVs, in view of the synthetic versatility of the carboxyl group towards various commonly used linkage groups (e.g., amides, esters). The

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• alkyne by oxidative amidation using carbon tetrachloride with propargylamine. The microwave-assisted click-conjugation was performed on a solid phase upon completion of the DNA synthesis (Scheme 4). Lönnberg and co-workers prepared a thymidine modified at the 4’-position with an azidomethyl group to

Synthesis of carbohydrate-scaffolded thymine glycoconjugates to organize multivalency

• Anna K. Ciuk and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2015, 11, 668–674, doi:10.3762/bjoc.11.75

• )-catalyzed click reaction [21][22]. Before, the acid-labile isopropylidene protecting group was removed using 10% TFA in dichloromethane leading to mannoside 4, and then the azide function in 4 was converted in a Staudinger reduction [23] with simultaneous Boc-protection giving rise to mannoside 5 in high

• for eventual immobilisation of the final thymine glycoconjugate on a surface or for conjugation to another multivalent compound. For the click reaction of 5 with the thymine derivative 6, copper sulfate and sodium ascorbate were used. The conjugation product 7 was obtained in 71% yield and showed good

• (Scheme 2). Staudinger reduction of the azide group and Boc-protection in the same pot gave 9 and subsequent click reaction with the thymine derivative 6 the isopropylidene-protected dimeric thymine glycoconjugate 10 in good yield. This could be alkylated employing the bromoethyl mannoside 11 [11] in an

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors

• Joana Salta,
• Jens Dernedde and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2015, 11, 638–646, doi:10.3762/bjoc.11.72

• . Unfortunately, only a few of our prepared compounds were sufficiently soluble in water to be suitable for the SPR test. However, a series of other multivalent conjugates was synthesized by using click chemistry with the azide derived from aminopyran 1 and results will be published in due time [40]. Conclusion

Synthesis of a hexasaccharide partial sequence of hyaluronan for click chemistry and more

• Marina Bantzi,
• Stephan Rigol and
• Athanassios Giannis

Beilstein J. Org. Chem. 2015, 11, 604–607, doi:10.3762/bjoc.11.67

• Abstract In the present work, the synthesis of a hexasaccharide partial sequence of hyaluronan equipped with a terminal azido moiety is reported. This hexasaccharide can be used for the attachment on surfaces by means of click chemistry and after suitable deprotection for biophysical studies. Keywords

• : azide; click chemistry; extracellular matrix; hexasaccharide; hyaluronan; multivalency; Introduction Much effort has been exerted during the last years to refine current knowledge about the biology of the extracellular matrix (ECM) [1]. While in the past, it was only regarded as a “space filler” among

• , allowing it to be used for surface modification via click chemistry. After suitable deprotection it can be used for biophysical studies by interaction with an alkyne group of suitably prepared proteins or proteoglycans giving the opportunity to gain deeper insights into ECM processes. Eventually, this

Synthesis and surface grafting of a β-cyclodextrin dimer facilitating cooperative inclusion of 2,6-ANS

• Lars W. Städe,
• Thorbjørn T. Nielsen,
• Laurent Duroux,
• Reinhard Wimmer,
• Kyoko Shimizu and
• Kim L. Larsen

Beilstein J. Org. Chem. 2015, 11, 514–523, doi:10.3762/bjoc.11.58

• 140, DK-8000 Aarhus, Denmark 10.3762/bjoc.11.58 Abstract A novel β-cyclodextrin (β-CD) dimer was synthesized and surface-grafted by click chemistry onto azide-functionalized quartz surfaces in order to introduce the cooperative features of the β-CD dimer to solid surfaces. Using NMR and fluorescence

• to parent β-CD) for the inclusion of lipophilic molecules [5][9]. The extensive research on the topic has generated a vast number of different β-CD-dimer constructs and methods for the synthesis thereof. Of these methods, synthesis by click chemistry (and specifically the copper(I)-catalyzed azide

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

• films from water contact angles of 140° down to 40°. Keywords: band-gap engineering; “click”-chemistry; conducting polymers; electropolymerization; Raman spectroscopy; surface functionalization; Introduction The many different applications of conducting polymers demand for tailored properties

• and alkynes (“click”-reaction) is a commonly used reaction in post-polymerization processes [39][40]. In the case of the azidomethyl-modified EDOT (EDOT-N3) building block different approaches of modifying the corresponding polymer PEDOT-N3 have been conducted so far, including the modification of

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

• by exploiting a click chemistry reaction of 5’-azido-2’-oxa-3’-aza-4’a-carbanucleosides with substituted alkynes. Biological tests indicate an antitumor activity for the synthesized compounds: most of them inhibit cell proliferation of Vero, BS-C-1, HEp-2, MDCK, and HFF cells with a CC50 in the range

• 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

• Sharpless [46] (Scheme 1 and Table 1). The click chemistry process, carried out with equimolar amounts of the respective dipolarophiles, afforded in all the cases the corresponding C-5’-triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides 13 and 14 in good yields (79–89%). According to other copper-catalyzed azide

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• , ICMPE, CNRS and University Paris Est, 2 rue Henri Dunant, 94320 Thiais, France 10.3762/bjoc.11.14 Abstract Novel (S)-camptothecin–dextran polymers were obtained by “click” grafting of azide-modified (S)-camptothecin and alkyne-modified dextrans. Two series based on 10 kDa and 70 kDa dextrans were

• were based on a 10 kDa and 70 kDa dextran backbone, respectively, which had been modified with alkynes by reaction with glycidyl propargyl ether (GP) as previously described [15]. The subsequent CuAACs with the alkyne-modified dextrans were made in DMSO using standard “click” conditions with 5 mol % Cu

• (I) compared to alkynes, stabilized with TBTA (Scheme 2). In order to maintain a reductive environment 15 mol % sodium ascorbate was added. The “click” conjugation was achieved within 24 hours at ambient temperature. The complete conversion of terminal alkyne protons with corresponding appearance of

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• functionalizations in terminal positions. First applications were presented with pyrene, cinnamoyl and anthracenyl labelled ARs. Keywords: articulated rods; click chemistry; molecular rods; oligospiroketals; pyrene excimer; Introduction One of the basic principles in living nature is based on shape-persistent and

• defined a 1,2,3-triazole containing linkage between two piperidine rings as the flexible joint F, which should be easily accessible by copper-catalyzed cycloaddition between an azide G and a terminal alkyne H (CuAAC, “Click” reaction) [16]. Primary alcohols I serve as “protected” azides accessible by

• Et3N (Scheme 2). With the first articulated rod 11 in hands we investigated whether it is possible to selectively activate the “click-functionalities” again. To our delight 11 could be converted in good yields both to the unprotected alkyne 12 and to the azide 13. Coupling of these articulated rods

Efficient deprotection of F-BODIPY derivatives: removal of BF₂ using Brønsted acids

• Mingfeng Yu,
• Joseph K.-H. Wong,
• Cyril Tang,
• Peter Turner,
• Matthew H. Todd and
• Peter J. Rutledge

Beilstein J. Org. Chem. 2015, 11, 37–41, doi:10.3762/bjoc.11.6

• ) effects this conversion in near-quantitative yields. Compared to existing methods, these conditions are relatively mild and operationally simple, requiring only reaction at room temperature for six hours (TFA) or overnight (HCl). Keywords: Brønsted acids; click chemistry; deboration; dipyrrins; F-BODIPYs

• reacted respectively with the complementary propargyl-tri-Boc cyclam 12 [23][32] and 2-azidoethyl-tri-Boc cyclam 13 [24][25] under the modified click conditions we have reported previously [24] to generate the Boc-protected triazolyl-cyclam/F-BODIPY conjugates 3 and 4 in excellent yields. In attempting to

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• linking reactions like, e.g., click reactions or amide bonds, the Glaser coupling allows the use of truly identical monomers. This decreases the number of steps for appropriate starting materials, and allows access to true homodimers in sensu strictu. Results and Discussion To achieve the synthesis of