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

(Pseudo)amide-linked oligosaccharide mimetics: molecular recognition and supramolecular properties

• José L. Jiménez Blanco,
• Fernando Ortega-Caballero,
• Carmen Ortiz Mellet and
• José M. García Fernández

Beilstein J. Org. Chem. 2010, 6, No. 20, doi:10.3762/bjoc.6.20

• followed by treatment with yellow mercury (II) oxide [68]. There are two general strategies to access pseudoamide-type oligosaccharide mimics: i) nucleophilic addition of sugar derivatives to carbohydrate isocyanates, isothiocyanates or isocyanides; and ii) conversion of sugar azides into glycosyl

Synthetic incorporation of Nile Blue into DNA using 2′-deoxyriboside substitutes: Representative comparison of (R)- and (S)-aminopropanediol as an acyclic linker

• Daniel Lachmann,
• Sina Berndl,
• Otto S. Wolfbeis and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2010, 6, No. 13, doi:10.3762/bjoc.6.13

• ” ligation strategy has become an important strategy for postsynthetic labeling of DNA [12][13]. Huisgen described first the [2+3]-cycloaddition between alkynes and azides yielding 1,2,3-triazoles [14]. The utility of this reaction as a bioligation method has grown incredibly after Meldal [15] and – almost

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• (Scheme 12) [49]. Recently, Cozzi et al. showed that FC benzylations can proceed even without adding a Lewis acid catalyst, just “on water” at 80 °C. However, this method is restricted to reactive heteroarenes such as indole (30), pyrrole and nucleophiles including azides or acetylacetonates. Moreover

Influence of spacer chain lengths and polar terminal groups on the mesomorphic properties of tethered 5-phenylpyrimidines

• Gundula F. Starkulla,
• Elisabeth Kapatsina,
• Angelika Baro,
• Frank Giesselmann,
• Stefan Tussetschläger,
• Martin Kaller and
• Sabine Laschat

Beilstein J. Org. Chem. 2009, 5, No. 63, doi:10.3762/bjoc.5.63

• nucleophilic substitution. The mesomorphic behaviour of these compounds was investigated by differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X-ray diffraction (WAXS and SAXS) and revealed smectic A mesophases for bromides, chlorides and azides 3, 4 and 6. For these compounds a

• treatment with 5-bromopentanol or 6-bromohexanol, the hydroxy compounds 5d and 5e were isolated in 76% and 80% yield, respectively. To obtain the azides 6, bromides 3a–e were treated with NaN3 in DMF at 100 °C for 24 h and the products 6a–e were isolated in 74% up to quantitative yield (Scheme 4). In a

• melting transitions at 76 °C and 75 °C for compounds 5a,b and at 77 °C, 86 °C, 67 °C and 68 °C for the azides 7b–e, respectively (upon heating or cooling) in the DSC curve. Presumably, the higher polarity of the terminal hydroxy group with respect to the azido group, together with hydrogen bonding

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• the planned construction of the aziridine by tandem SN2 displacement. Exploiting the facial selectivity of compound 38, the direct introduction of an aziridine equivalent was attempted by 1,3-dipolar cycloaddition of an alkyl azide. As Frank noted, cycloaddition of azides to 3H-pyrrolo [1,2-a]indoles

• eclipsed by the olefinic hydrogen (compound 55) to minimize 1,3-allylic strain (Scheme 15) [61]. Attempts to introduce the aziridine from the olefin 48 using halogeno-azides like BrN3 or IN3 and subsequent reduction failed because the compound oxidized rapidly to the indoloquinone 58 (Scheme 16). A longer

Controlling hazardous chemicals in microreactors: Synthesis with iodine azide

• Johan C. Brandt and
• Thomas Wirth

Beilstein J. Org. Chem. 2009, 5, No. 30, doi:10.3762/bjoc.5.30

• Johan C. Brandt Thomas Wirth Cardiff University, School of Chemistry, Park Place, Cardiff CF10 3AT, UK. 10.3762/bjoc.5.30 Abstract Aromatic aldehydes have been converted into the corresponding carbamoyl azides using iodine azide. These reactions have been performed safely under continuous flow

• potentially hazardous compounds is another advantage of microreactors as only very small amounts of compounds/reagents are handled. Large inventories of dangerous reagents and intermediates are not necessary. Azides are among the most versatile reagents in modern organic chemistry however they are not often

• used to their full potential due to safety concerns. Especially azides with low molecular weights are difficult to handle because of their high disposition to detonate [3][4][5]. However, azides are extremely useful moieties in organic synthesis as they can be transformed easily into a large variety of

Dimerization of propargyl and homopropargyl 6-azido- 6-deoxy- glycosides upon 1,3-dipolar cycloaddition

• Nikolas Pietrzik,
• Daniel Schmollinger and
• Thomas Ziegler

Beilstein J. Org. Chem. 2008, 4, No. 30, doi:10.3762/bjoc.4.30

• -tetra-O-acetyl-glycosyl azides and ethyl 2,3,4-tri-O-acetyl-6-azido-6-deoxy-1-thio-glycosides, respectively [12]. In order to increase the structural diversity of glycosyl amino acid building blocks containing 1,2,3-triazole spacers even more, we next looked at the possibility to use glycosides bearing

Synthesis of 2-substituted 9-oxa-guanines {5-aminooxazolo[5,4-d]pyrimidin- 7(6H)-ones} and 9-oxa-2-thio- xanthines {5-mercaptooxazolo[5,4-d]pyrimidin- 7(6H)-ones}

• Subrata Mandal,
• Wen Tai Li,
• Yan Bai,
• Jon D. Robertus and
• Sean M. Kerwin

Beilstein J. Org. Chem. 2008, 4, No. 26, doi:10.3762/bjoc.4.26

• with benzyl azide or 2-morpholinoethyl azide in the presence of catalytic CuSO4 and sodium ascorbate to afford the triazoles 9 and 10, respectively, in good yield (Figure 5). The copper-catalyzed Huisgen cycloaddition of terminal alkynes and alkyl azides favors formation of the 1,4-triazole

Synthesis of new triazole- based trifluoromethyl scaffolds

• Michela Martinelli,
• Thierry Milcent,
• Sandrine Ongeri and
• Benoit Crousse

Beilstein J. Org. Chem. 2008, 4, No. 19, doi:10.3762/bjoc.4.19

• ]. The copper(I)-catalyzed 1,3-dipolar cycloaddition [33][34][35][36][37][38] of organic azides and alkynes (also called “click chemistry”) resulting in the formation of 1,2,3-triazoles has become an increasingly attractive area [39]. According to the literature [33][34][35][36][37][38], the Cu(I

• the presence of CuI (10 mol%) and showed good reactivity with completion of the reaction within 24 h, whereas the use of CuSO4/Na ascorbate afforded the cycloadduct in low yield. The reaction was then carried out with different propargylamines (N-(p-methoxyphenyl) and N-benzyl) and various azides at

• scaffolds from readily accessible propargylamines and azides through a copper (I) catalyzed 1,3-dipolar cycloaddition. The triazole derivatives were obtained in good yields and will be useful intermediates for further synthesis of new fluorinated foldamers and their conformational feature studies

Synthesis of crispine A analogues via an intramolecular Schmidt reaction

• Ajoy Kapat,
• Ponminor Senthil Kumar and
• Sundarababu Baskaran

Beilstein J. Org. Chem. 2007, 3, No. 49, doi:10.1186/1860-5397-3-49

• intramolecular Schmidt reaction of azides with carbonyl compounds.[11][12] Pearson and Aube have exploited the synthetic potential of the intramolecular Schmidt reaction in the synthesis of several indolizidine alkaloids. [11][12][13][14][15] Recently, we reported a novel approach for the construction of the

Synthesis of coumarin or ferrocene labeled nucleosides via Staudinger ligation

• Ivana Kosiova,
• Andrea Janicova and
• Pavol Kois

Beilstein J. Org. Chem. 2006, 2, No. 23, doi:10.1186/1860-5397-2-23

• Ivana Kosiova Andrea Janicova Pavol Kois Comenius University, Faculty of Natural Sciences, Department of Organic Chemistry, Mlynska dolina, Pavilon CH2, SK-84215 Bratislava, Slovak Republic 10.1186/1860-5397-2-23 Abstract Background Reaction of azides with triaryl phosphines under mild conditions

• starting compounds for preparation of modified nucleosides are azidonucleosides. In general, organic azides are valuable, energy-rich and flexible intermediates, which can react very differently under various reaction conditions. [13] They can react at N1 with electrophiles (carbon electrophiles, protons

• , boranes) and at N3 with nucleophiles, very frequently with phosphorous nucleophiles. Reaction of azides with triaryl phosphines under mild conditions gives iminophosphoranes without formation of any byproducts. [14] The intermediate which is formed almost quantitatively can be rapidly hydrolysed to the