Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• = 6,300 M−1) which is embedded in an axle molecule with two azide residues. The second station, the dihydroxynaphthalene moiety (green), displays a lower association constant of Ka = 5,800 M−1. The pseudorotaxane precursor was end-capped by a double copper-catalyzed azide–alkyne click reaction in CH2Cl2

• arrangement. Starting from the pre-assembled catenane, the axle molecule is threaded through the wheel and end-capped by a copper-catalyzed click reaction. A variety of different spectroscopic and electrochemical methods was applied to reveal the switching behavior of 24 and its stable co-conformations in

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• amide reaction between compound 6 and 6-azidohexan-1-amine in the presence of 2-chloro-4,6-dimethoxy-1,3,5-triazine and N-methylmorpholine. Finally, the classical and effective “Click” reaction was used to produce the target compound [2]rotaxane R1. The crown ether 9 and dibenzylammonium ion (R2NH2

An amphiphilic pseudo[1]catenane: neutral guest-induced clouding point change

• Tomoki Ogoshi,
• Tomohiro Akutsu and
• Tada-aki Yamagishi

Beilstein J. Org. Chem. 2018, 14, 1937–1943, doi:10.3762/bjoc.14.167

• (CuAAC) ‘‘click’’ reaction (see details in the experimental section). In addition, model compound 4 was also synthesized as a reference (Figure 1d). Compound 3 is soluble in various organic and aqueous solvents as it comprises eight amphiphilic tri(ethylene oxide) chains. We investigated the

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• -triazine dendrimers exhibiting mesogenic behaviour. The first cases known so far refer to N-substituted G-0-3 dendritic melamines [19][20][21] with n-octyl peripheral groups as unconventional columnar liquid crystals and G-0 tris(triazolyl)triazines (available via the “click” reaction between 2,4,6-tris

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• reaction conditions together with very high and reverse regioselectivity and efficiency (in most cases 85–99% yields) makes the CuSAC reaction a very good alternative to the well-established azide–alkyne click-reaction [117] useful not only in classical organic synthesis but also in bioconjugation

• reaction conditions (aqueous t-BuOH solution at 60 °C) and can be considered as a good illustration of the click-reaction. Another important example of sydnone cycloaddition involves a very fast reaction with strained seven- or eight-membered cycloalkynes (strain-promoted sydnone alkyne cycloaddition

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• betulinic acid analogs were synthesized by using azide–alkyne click reaction and their anticancer activities against different cancer cell lines and normal human PBMC cell line were evaluated by MTT assay. Conjugate 42 was found to be extremely potent against HT-29 cell line with an IC50 value of 14.9 μM

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• (Scheme 5) [42]. In the absence of light, azobenzene derivatives were isolated as the pure E-isomers. In their original report, Sharpless and co-workers described the use of copper turnings to promote a regioselective azide–alkyne [3 + 2]-cycloaddition ("click") reaction over 24 hours [43]. High-speed

• ) Crude solid ball mill click reaction mixture after removal from copper vessel (left) and during extraction of pure product with DMSO (right). Early low temperature mechanised ball mill as described by Mudd et al. – adapted from reference [78]. Materials used to prepare a smectic phase. Structures of 5

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• further stabilizes the complex, and this structure is energetically more favorable. These results prompted us towards the synthesis and evaluation of this promising molecule. Synthesis The synthesis of UHF is depicted in Scheme 1. UHF was synthesized by the CuAAC (click) reaction of 7-propargyloxy-3

• , DMSO-d6) δ 11.29 (s, 1H, 3-uracil NH), 10.99 (s, 1H, 1-uracil NH), 7.64 (s, 1H, 6-uracil CH), 4.02 (s, 2H, CH2); 13C NMR (75 MHz, DMSO-d6) δ 163.97 (C=O6-uracil), 151.23, 141.94 (CH4-uracil), 106.72 (C5-uracil), 46.56 (CH2). Uracil-hydroxyflavone probe (UHF): The click reaction of 3 and 4 was performed

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• 1,4-disubstituted triazoles 8 through click reaction between 2-azidomethyl-4,5-diaryloxazoles and alkynes in the presence of a copper(I) catalyst (Scheme 2). The authors were able to synthesize an array of small-molecule peptidomimetics that inhibited Porphyromonas gingivalis biofilm formation [34

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• [22]. There are not many transformations of aliphatic SF5 compounds described in the literature. Among them are the preparation and derivatization of SF5-aldehydes [23], Diels–Alder reactions [24][25][26], the “click reaction” of SF5-acetylenes with azides to form triazoles [27], and 1,3-dipolar

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• acetylene-functionalized Thermomyces lanuginosus lipase was then attached to these azide-functionalized water-soluble AuNPs by CuAAC (Scheme 7). It was found that the enzyme retained its activity after the click reaction. However, the vast excesses of both Cu (a one million-fold excess relative to the azide

• [62]. They reasoned that one important consideration that needed to be addressed to enable an efficient click reaction was the solubility of the reagents; in particular alkanethiol-functionalized AuNPs are generally only soluble in organic solvents, whereas water is required to dissolve the CuSO4

• of ascorbic acid and Cu(I) was also increased to a stoichiometric amount with respect to the alkyne and azide. Finally the click reaction was performed under an inert atmosphere. The authors reported that if any of the above-mentioned conditions were not met, then the reaction gave a very poor yield

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• bond bioisosteres made the click reaction a valuable synthetic methodology for conjugation of bioactive molecules [7][8][9] aiming to improve their biological activities [4][10][11]. Discovery of copper(I) ion catalysis in azide–alkyne cycloadditions was decisive for applications of this reaction, as

• click reaction to provide the target 6-phenyl-2-(trifluoromethyl)quinolines containing p-halogen-substituted and non-substituted phenyl-1,2,3-triazole unit attached at the O-4 position of the quinoline fragment. All triazole products have almost identical conformations in the solid state, with no

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• ] or trifluoroethoxy (12) [82] group have been reported. These dimers were synthesized from A3B type phthalocyanines containing an ethynyl group and 1,4-bis(azidomethyl)benzene via a so-called “double-click reaction” [83] catalyzed by CuI. The examination of the spectroscopic properties of these dimers

• the repulsive effect of the trifluoroethoxy group. More interestingly, similar aggregation behaviors were also suggested for trinuclear phthalocyanines that can aggregate more easily [84]. These trinuclear phthalocyanines were synthesized by a triple click reaction. The tert-butyl-substituted trimer

• TFEO-ZnPc 4 and fluorinated polymer 22 were condensed by a click reaction between azide and alkyne groups (Scheme 8). The graft ratio of the TFEO-ZnPc-supported fluoropolymer was calculated from the area ratio of 19F NMR, and the resulting fluorinated copolymers showed different grafting ratios (from

Curcuminoid–BF₂ complexes: Synthesis, fluorescence and optimization of BF₂ group cleavage

• Henning Weiss,
• Jeannine Reichel,
• Helmar Görls,
• Kilian Rolf Anton Schneider,
• Mathias Micheel,
• Michael Pröhl,
• Michael Gottschaldt,
• Benjamin Dietzek and
• Wolfgang Weigand

Beilstein J. Org. Chem. 2017, 13, 2264–2272, doi:10.3762/bjoc.13.223

• decided to synthesise a range of curcuminoids bearing propargyl and pent-1-yn-5-yl ether groups as partners for “click” reactions [26]. We already observed that for the BF2 complex of bispropargyl functionalised bisdemethoxycurcumin, the BF2 group was hydrolysed under regular “click” reaction conditions

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• magnetic resonance imaging (MRI) [22]. Well-defined fluorescent polyrotaxanes with alternating, threaded cucurbit[6]uril and CD rings were assembled by Fraser Stoddart’s group via an alkyne–azide click reaction exploiting supramolecular catalysis [23][24]. The concurrent radical copolymerization of 1,3

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• size of the macrocycle formed during the glycosylation (Scheme 12) [80][81]. Thioglycoside donor 45 containing a 2-O-propargyl group and acceptor 46 with an azide-containing protecting group were connected using a click reaction to afford the tethered intermediate 47. Upon treatment with NIS/TfOH

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• synthesize the triazole rings with additional 1 equiv of K2CO3 which resulted in >85% of product (Scheme 37b). Mack and co-workers reported another mechanochemical variation of “click” reaction [153][154] where they could isolate 33–90% of triazole derivatives using copper reaction vial in ball mill for 16 h

• particles [146]. Mechanochemical synthesis of 1,2-di-substituted benzimidazoles [149]. Mechanochemical click reaction using an alumina-supported Cu-catalyst [152]. Mechanochemical click reaction using copper vial [155]. Mechanochemical indole synthesis [157]. Mechanochemical synthesis of chromene [158

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• blocks were coupled via 1,3-dipolar cycloaddition (click reaction) iteratively through the development of a greener base-free Cu(I)-catalyzed azide–alkyne cycloaddition reaction. The cycloadducts were then converted to macrocycles by Ru-catalyzed cyclization reaction using greener and non-hazards

• ratio of integration of the terminal alkyne proton in the propargyl building block and the characteristic triazole–alkene proton in the cyclo-adducts. The click reaction proceeds under various conditions with a plenty of sources of Cu(I) [19]. We have selected copper iodide (CuI) as Cu(I) source for the

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• employed for this purpose (i.e., click reaction, amidation, conjugation via carbonyldiimidazol and perfluorophenyl azide (PFPA) photo-coupling) have to be compatible with water, the common medium for AuNP preparation [25][26][27][28][29]. One example of the three-step approach was described by Tian and co

Automating multistep flow synthesis: approach and challenges in integrating chemistry, machines and logic

• Chinmay A. Shukla and
• Amol A. Kulkarni

Beilstein J. Org. Chem. 2017, 13, 960–987, doi:10.3762/bjoc.13.97

• the multistep synthesis of rufinamide, an antiepileptic agent [14] (Scheme 3). The process involves three steps namely azide synthesis, amide synthesis and click reaction or azide–alkyne cycloaddition. For the azide synthesis, the aryl bromide (1 equiv) and sodium azide (1.3 equiv) are reacted in a

Fast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction

• Qi An,
• Youssef Hassan,
• Xiaotong Yan,
• Peter Krolla-Sidenstein,
• Tawheed Mohammed,
• Mathias Lang,
• Stefan Bräse and
• Manuel Tsotsalas

Beilstein J. Org. Chem. 2017, 13, 558–563, doi:10.3762/bjoc.13.54

• induced thiol–yne click reaction. Using this reaction, we could greatly enhance the CMP nanomembrane synthesis and further broaden the variability of the LbL approach. Keywords: click chemistry; conjugated microporous polymers (CMPs); microporous materials; nanomembranes; thin films; thiol–yne coupling

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• introducing small, terminal alkyne functionalities at common sites of the adenine base. Upon successful incorporation into PAR, these alkynes serve as handles for copper(I) catalysed azide–alkyne click reaction (CuAAC) [22] with fluorescent dyes. Terminal alkynes are the smallest possible reporter group that

• + analogue or a 1:1 mixture. Then, copper(I)-catalysed azide–alkyne click reaction (CuAAC) is performed and mixture is resolved by SDS PAGE. SDS PAGE analysis of ADP-ribosylation of histone H1.2 with ARTD1, ARTD2, ARTD5 and ARTD6 using NAD+ analogue 1. Upper panel shows Coomassie Blue staining; lower panel

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

• from the resin and deprotected with conc. NH4OH at 45 °C for 16 h. Click reaction with modified oligonucleotides. To the lyophilized alkyne-modified DNA sample were added water (100 µL), sodium ascorbate (25 µL of 0.4 M in water), tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (34 µL of 0.1 M in

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• . This was exemplarily demonstrated by the hydrogenation of syn-21 and anti-24 and by a click reaction of a 5-alkynyl-substituted precursor. Keywords: amino alcohol; click reaction; cross-coupling reactions; hydrogenation; iodination; 1,2-oxazines; Introduction Over the last decade, we have intensively

• -oxazines bearing the newly installed alkynyl group at C-5 are ideal candidates for efficient subsequent transformations. A very popular and widely applied reaction of terminal alkynes is the copper-catalyzed azide–alkyne cycloaddition, also termed as click reaction, efficiently leading to 1,4-disubstituted

• . Cross-coupling reaction of 1,2-oxazine anti-4d leading to 5-cyano-substituted 1,2-oxazine anti-25. Desilylation of 1,2-oxazine syn-5 and subsequent click reaction with benzyl azide leading to 5-(1,2,3-triazolyl)-substituted 1,2-oxazine syn-26. Hydrogenation of 1,2-oxazine syn-21 leading to γ-amino