Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• co-workers on high-spin iron–imido complexes generated by the reactions of alkyl azides with FeCl2 bearing dipyrromethene ligands revealed the radical character of the complex [39][40], harmonizing well with our result, which implies the intermediacy of the nitrogen radical species. Conclusion We

Superstructures of fluorescent cyclodextrin via click-reaction

• Arkadius Maciollek,
• Helmut Ritter and
• Rainer Beckert

Beilstein J. Org. Chem. 2013, 9, 827–831, doi:10.3762/bjoc.9.94

• opens up a wide field of modification through click chemistry with azides or thioles [6][7]. Accordingly, following our former work with mono azide modified CD, we were encouraged to combine the fluorescent hydroxythiazole dye with CD [8][9][10]. Such water soluble spectroscopically active hosts can be

High-spin intermediates of the photolysis of 2,4,6-triazido-3-chloro-5-fluoropyridine

• Sergei V. Chapyshev,
• Denis V. Korchagin,
• Patrik Neuhaus and
• Wolfram Sander

Beilstein J. Org. Chem. 2013, 9, 733–742, doi:10.3762/bjoc.9.83

• associated with strong π-conjugation of these groups with the pyridine ring. On photoexcitation, such azido groups are more efficiently involved in reorganization of the molecular electronic system and more easily adopt geometries of the locally excited predissociation states. Keywords: azides; EPR

• when an additional line-broadening parameter Γ(E) was used in the spin-Hamiltonian calculations [24]. The necessity of the use of this parameter in calculations is due to the presence in matrices of numerous conformational isomers of the starting azides. Upon UV irradiation, these conformers decompose

• quintet dinitrene 16. One also cannot exclude that the photoexcitation of quintet azidonitrenes into predissociation states is a much less efficient process in comparison with the photoexcitation of singlet azides. In contrast to singlet azides, quintet azidonitrenes already have four singly occupied

Microwave-assisted three-component domino reaction: Synthesis of indolodiazepinotriazoles

• Rajesh K. Arigela,
• Sudhir K. Sharma,
• Brijesh Kumar and
• Bijoy Kundu

Beilstein J. Org. Chem. 2013, 9, 401–405, doi:10.3762/bjoc.9.41

• methodology has been demonstrated by treating various 2-alkynylindoles (aromatic/aliphatic) with epichlorohydrin and sodium azide furnishing annulated tetracyclic indolodiazepinotriazoles in satisfactory yields. Keywords: 2-alkynylindoles; azides; 1,3-dipolar cycloaddition; domino reaction

• increasing attention in drug discovery processes [17][18]. The ease of reaction in the intermolecular format has been successfully demonstrated by using both organic/inorganic azides as well as alkynes/diynes [19][20][21]. In contrast to its employment in an intermolecular format, intramolecular azide–alkyne

Towards a biocompatible artificial lung: Covalent functionalization of poly(4-methylpent-1-ene) (TPX) with cRGD pentapeptide

• Lena Möller,
• Christian Hess,
• Jiří Paleček,
• Yi Su,
• Axel Haverich,
• Andreas Kirschning and
• Gerald Dräger

Beilstein J. Org. Chem. 2013, 9, 270–277, doi:10.3762/bjoc.9.33

• , by the use of Huisgen-type “click” chemistry (Scheme 2). cRGD pentapeptide 1b was prepared in sufficient amounts by solution-phase chemistry [23]. Because of the disadvantage associated with copper-mediated 1,3-cycloadditions of alkynes with azides in biological or biomedical applications we

Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

• Daniel Fürniss,
• Timo Mack,
• Frank Hahn,
• Sidonie B. L. Vollrath,
• Katarzyna Koroniak,
• Ute Schepers and
• Stefan Bräse

Beilstein J. Org. Chem. 2013, 9, 56–63, doi:10.3762/bjoc.9.7

• -alkylation with 5-chloropent-1-yne to insert the terminal alkyne moiety. To accomplish that, we used 10.0 equiv of alkyne and 15.0 equiv of K2CO3 in DMF; the reaction led to resin 9 with virtually quantitative yield, as shown in Scheme 1. For the CuAAC with the azides moieties 4, 6 and 7, respectively, we

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• catalytic efficacy. Subsequently, we explored the extension of this approach to the development of a chemoselective three-component one-pot reaction. Thus, we found that alkyl bromides 2 could be directly employed as user-friendly substrates for the in situ formation of the corresponding organic azides

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• polar multiple bonds. Related reactions have been observed for terminal oxo, sulfido, phosphinidene, and alkylidyne complexes of early transition metals (see references [30][31][32][33] for representative examples). Similar reactions can also occur in [3 + 2] fashion with azides [34]. As for main-group

• -metal (or "Roper-type") carbenes with significant π backbonding, consistent with Roper's predicted patterns of reactivity for metal–carbon double bonds [75]. These Roper-type carbenes also reacted with organic azides and nitrous oxide via an apparent [3 + 2] cycloaddition [76][77], leading to oxygen

• -atom or nitrene-group transfer and formation of (PNP)Ir–N2 [78], and this reaction was utilized in catalytic C–H functionalization (see below). More recently, Hillhouse's nickel carbenes and imides have been shown to exhibit similar reactivity with organic azides, though reaction with CO2 has not been

Photochemistry with laser radiation in condensed phase using miniaturized photoreactors

• Elke Bremus-Köbberling,
• Arnold Gillner,
• Frank Avemaria,
• Céline Réthoré and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1213–1218, doi:10.3762/bjoc.8.135

• . Keywords: azides; chemical diversity; flow chemistry; heterocycles; laser; micro reactor; Introduction Classical combinatorial chemistry [1][2] approaches usually aim at the synthesis of multi-milligram amounts of new compounds to extend screening decks used in multiple screening campaigns [3]. An

• the wavelength is close to that of the applied UV-lamp, 355 nm is usually within the absorption area of azides, and this laser type is commonly used in most laser labs. We applied a single-pulse power of 0.16 to 3 W resulting in pulse energies between 4 and 87 nJ and energy densities of approximately

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• yields of 78–98% (Table 3). Conclusion Diaryltriazoles were obtained in an efficient three-step solid-phase procedure. Immobilization of aromatic azides on commercial Wang resin followed by copper(I)- or ruthenium(II)-catalyzed 1,3-cycloaddition and subsequent cleavage of the product from the resin gave

• – Huisgen 1,3-dipolar cycloaddition of solid-phase-immobilized azides with terminal alkynes by copper(I) catalysis: An azide-functionalized Wang resin 7 or 9 (1 equiv) was preswollen in dimethylformamide (1.5 mL/100 mg resin) for 2 h at room temperature. The copper(I) catalyst was prepared in situ by using

• steps with water, dimethylformamide, methanol and dichloromethane (each solvent 3 × 2 mL/100 mg resin) were carried out. GP 3 – Huisgen 1,3-dipolar cycloaddition of solid-phase-immobilized azides with terminal or internal alkynes by ruthenium(II) catalysis: The azide functionalized Wang resin (1 equiv

High-affinity multivalent wheat germ agglutinin ligands by one-pot click reaction

• Henning S. G. Beckmann,
• Heiko M. Möller and
• Valentin Wittmann

Beilstein J. Org. Chem. 2012, 8, 819–826, doi:10.3762/bjoc.8.91

• explanation for the observed binding affinities. Results and Discussion Synthesis of glycoclusters The Cu(I)-catalyzed [49][50] Huisgen [3 + 2] cycloaddition [51] of azides and alkynes (CuAAC) is a frequently used method for the covalent attachment of carbohydrate epitopes to azide- or alkyne-presenting

• ) comprising different spacer geometries were selected. These amines were employed in the sequential one-pot procedure [48] for diazo transfer and CuAAC (Table 1). First, the Cu(II)-catalyzed diazo transfer was performed at ambient temperature until complete conversion of the amines to azides. Then, CuAAC was

• azides (see Supporting Information File 1 for full experimental data). According to TLC all reactions (except for B6) proceeded with complete conversion of the amines to the desired glycoconjugates. However, some loss of material during purification of the acetylated chitobiose derivatives by flash

Thiophene-based donor–acceptor co-oligomers by copper-catalyzed 1,3-dipolar cycloaddition

• Stefanie Potratz,
• Amaresh Mishra and
• Peter Bäuerle

Beilstein J. Org. Chem. 2012, 8, 683–692, doi:10.3762/bjoc.8.76

• high yield and purity. Click reactions generally involve a Cu(I)-catalyzed version of the Huisgen 1,3-dipolar cycloaddition of terminal acetylenes and azides (CuAAC), to regioselectively yield 1,4-disubstituted 1H-1,2,3-triazoles [11][12]. In the meanwhile, this type of click reaction has become very

• synthesize aromatic azides from halogenated arenes and sodium azide. We have now transferred this method to the synthesis of 3-azidothiophene (2) from 3-iodothiophene (1) in excellent yield, which in the following was used for further click reactions to form novel thienyl-1,2,3-triazole co-oligomers (Scheme

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• that the redox-active macrocycle is capable of sensing chloride in CH3CN solution. Keywords: anion binding; C–H···anion interactions; electrochemistry; ferrocene; triazolium; Introduction The copper(I)-catalysed cycloaddition of alkynes and azides (CuAAC) [1][2] to give the 1,2,3-triazole group is

Synthesis of 2-amino-3-arylpropan-1-ols and 1-(2,3-diaminopropyl)-1,2,3-triazoles and evaluation of their antimalarial activity

• Matthias D’hooghe,
• Stéphanie Vandekerckhove,
• Karen Mollet,
• Karel Vervisch,
• Stijn Dekeukeleire,
• Liesbeth Lehoucq,
• Carmen Lategan,
• Peter J. Smith,
• Kelly Chibale and
• Norbert De Kimpe

Beilstein J. Org. Chem. 2011, 7, 1745–1752, doi:10.3762/bjoc.7.205

• equiv of sodium azide in DMSO at 80 °C for 16 h (CAUTION) (Scheme 3). Subsequently, a CuI-catalyzed 1,3-cycloaddition of N-(arylmethyl)aziridine azides 14 was evaluated for the first time by utilizing one equiv of an arylacetylene in CH3CN under reflux for 16 h, furnishing a direct entry towards new 2

Continuous-flow enantioselective α-aminoxylation of aldehydes catalyzed by a polystyrene-immobilized hydroxyproline

• Xacobe C. Cambeiro,
• Rafael Martín-Rapún,
• Pedro O. Miranda,
• Sonia Sayalero,
• Esther Alza,
• Patricia Llanes and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2011, 7, 1486–1493, doi:10.3762/bjoc.7.172

• azides and alkynes (CuAAC) used as the immobilization strategy [44][45][46], led to improved efficiency, both in terms of catalytic activity and asymmetric induction, and different behaviour of the resulting materials in terms of hydrophilicity or hydrophobicity [47][48][49][50]. An even better

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• Lukas Kupracz Jan Hartwig Jens Wegner Sascha Ceylan Andreas Kirschning Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.7.168 Abstract The multistep flow synthesis of vinyl azides and their application in the synthesis of

• vinyltriazoles is reported. The synthesis relies on a stable polymer-bound equivalent of iodine azide that serves to carry out 1,2-functionalization of alkenes in a telescope flow protocol. The intermediate 2-iodo azides are subjected to a DBU-mediated polymer-supported elimination step yielding vinyl azides in

• reactor. Keywords: flow reactor; inductive heating; iodine azide; polymer-supported reagents; vinyl azides; Introduction Azides are highly versatile organic functional groups and their preparation and their reactivity are well explored [1]. In contrast, the synthesis of vinyl azides is far away from

Continuous flow photolysis of aryl azides: Preparation of 3H-azepinones

• Farhan R. Bou-Hamdan,
• François Lévesque,
• Alexander G. O'Brien and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2011, 7, 1124–1129, doi:10.3762/bjoc.7.129

• Berlin, Germany 10.3762/bjoc.7.129 Abstract Photolysis of aryl azides to give nitrenes, and their subsequent rearrangement in the presence of water to give 3H-azepinones, is performed in continuous flow in a photoreactor constructed of fluorinated ethylene polymer (FEP) tubing. Fine tuning of the

• reaction conditions using the flow reactor allowed minimization of secondary photochemical reactions. Keywords: azepinones; azides; continuous flow; nitrenes; photochemistry; Findings Although photochemical rearrangements are an important class of reactions for heterocycle synthesis [1][2], their use is

• ]. Overall, aryl azides, which are simple to prepare from the corresponding aniline derivative, are convenient precursors for the synthesis of azepine derivatives. However, the utility of the process is offset by the long reaction times required and by the low yields arising from poor selectivity and

A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins: Important synthons for the synthesis of chromogenic/fluorogenic protease substrates

• Xinghua Wu,
• Yu Chen,
• Herve Aloysius and
• Longqin Hu

Beilstein J. Org. Chem. 2011, 7, 1030–1035, doi:10.3762/bjoc.7.117

• [18][19] and its application to directly couple amino acids with azides [20]. We demonstrated that our selenocarboxylate/azide amidation does not involve reduction of the azide to amine and subsequent standard coupling reaction [18][19]. We also demonstrated that the selenocarboxylate/azide amidation

• was highly chemoselective, mild, and free of racemization in the coupling step [20]; was compatible with common protecting groups used in peptide chemistry including Fmoc, Boc, Cbz, and Trt; and more importantly, worked very efficiently for electron-deficient aromatic azides substituted with an

• to react with the selenocarboxylates derived from Nα-protected amino acids to form the desired amides. The azides can be readily prepared in excellent yields through diazotization of p-nitroaniline and 7-amino-4-methylcoumarin, followed by treatment with sodium azide, and, more importantly, the

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

•  34). Yamamoto’s group reported that intramolecular cyclization of 2-alkynylbenzyl azides 187 in the presence of AuCl3 and AgSbF6 in THF under pressure at 100 °C gives the corresponding isoquinolines 188 in good yields [85]. 4 Gold-catalyzed C–C bond formations The formation of carbon–carbon bonds by

Synthetic applications of gold-catalyzed ring expansions

• David Garayalde and
• Cristina Nevado

Beilstein J. Org. Chem. 2011, 7, 767–780, doi:10.3762/bjoc.7.87

• intermolecular nucleophilic attack to give intermediate 47, which upon cycloisomerization affords the aromatic product (Scheme 14, path b). Toste and co-workers reported an intramolecular acetylenic Schmidt reaction using azides as internal nucleophiles to give substituted pyrroles (Scheme 15) [42]. Gold

Brønsted acid-promoted azide–olefin [3 + 2] cycloadditions for the preparation of contiguous aminopolyols: The importance of disiloxane ring size to a diastereoselective, bidirectional approach to zwittermicin A

• Hubert Muchalski,
• Ki Bum Hong and
• Jeffrey N. Johnston

Beilstein J. Org. Chem. 2010, 6, 1206–1210, doi:10.3762/bjoc.6.138

• cycloaddition reactions exist, they rely on intramolecular azide delivery under thermal conditions [15][16][17][18][19][20][21]. Examples of substrate control in an acid-catalyzed intermolecular reaction of azides with alkenes are limited [22]. We report our initial study of the intermolecular

En route to photoaffinity labeling of the bacterial lectin FimH

• Thisbe K. Lindhorst,
• Michaela Märten,
• Andreas Fuchs and
• Stefan D. Knight

Beilstein J. Org. Chem. 2010, 6, 810–822, doi:10.3762/bjoc.6.91

• photoaffinity-labeling of FimH. Our earlier work suggested that diazirines are more useful photoactive groups than aryl azides and benzophenones [15]. Therefore, the synthesis of a biotin-labeled daizirine-functionalized mannoside was our next target. In this synthesis, aspartic acid was utilized as the

EPR and pulsed ENDOR study of intermediates from reactions of aromatic azides with group 13 metal trichlorides

• Giorgio Bencivenni,
• Riccardo Cesari,
• Daniele Nanni,
• Hassane El Mkami and
• John C. Walton

Beilstein J. Org. Chem. 2010, 6, 713–725, doi:10.3762/bjoc.6.84

• of Chemistry, University of St. Andrews, EaStChem, St. Andrews, Fife KY16 9ST, UK 10.3762/bjoc.6.84 Abstract The reactions of group 13 metal trichlorides with aromatic azides were examined by CW EPR and pulsed ENDOR spectroscopies. Complex EPR spectra were obtained from reactions of aluminium

• , gallium and indium trichlorides with phenyl azides containing a variety of substituents. Analysis of the spectra showed that 4-methoxy-, 3-methoxy- and 2-methoxyphenyl azides all gave ‘dimer’ radical cations [ArNHC6H4NH2]+• and trimers [ArNHC6H4NHC6H4NH2]+• followed by polymers. 4-Azidobenzonitrile, with

• its electron-withdrawing substituent, did not react. In general the aromatic azides appeared to react most rapidly with AlCl3 but this reagent tended to generate much polymer. InCl3 was the least reactive group 13 halide. DFT computations of the radical cations provided corroborating evidence and

Preparation of aminoethyl glycosides for glycoconjugation

• Robert Šardzík,
• Gavin T. Noble,
• Martin J. Weissenborn,
• Andrew Martin,
• Simon J. Webb and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2010, 6, 699–703, doi:10.3762/bjoc.6.81

• because it is commercially available, crystalline and can be easily deprotected in one step avoiding use of azides. Figure 1 lists the target aminoethyl glycosides (1–9) generated in this study (q.v. Scheme 1 and Table 1). The key glycosylation step is shown in Scheme 1 and the results of the different