Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

• subsequent transformations [19][22][26]. Examples of IMCR orthogonal species or functionalities are alkenes, alkynes and azides which may give the cyclic analogues via subsequent ring closing metathesis (RCM) or 1,3-dipolar cycloadditions. In contrast, protected functional groups first require a deprotection

• azides (Scheme 25) [85]. Advantages of this reaction are the kinetic stability of both functional groups under a range of different conditions. Also, the triazole products can be formed in both organic and aqueous solvents and by using the Cu(I)-catalyst which induces regioselective formation of the 1,4

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• emerged as a popular method. In particular, C-allyl glycosides, glycosyl cyanides, and glycosyl azides have received considerable attention, as the allyl, cyanide and azide moieties can be readily converted into a variety of other functional groups [6][28][29][30]. Furthermore, the resulting C

• with Me3SiCN afforded a 5:1 and 4:1 mixture of glycosyl cyanides 3 and 4 in 77% and 62% yields, respectively (Table 3). The reaction of glycals 1a and 1b with Me3SiN3 furnished a mixture of C-1 and C-3 substituted glycosyl azides (5/5' and 6/6'). This observation is in conformity with the report of

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• reaction of an ortho-(benzyloxy)benzylamine, glycolic acid, an isocyanide and an aldehyde, followed by an intramolecular Mitsunobu substitution was developed. The required ortho-(benzyloxy)benzylamines have been in situ generated from the corresponding azides, in turn prepared in high yields from salicylic

• benzyl azides by nucleophilic substitution, followed by azide reduction. This strategy required in any case protection of the phenol moiety. As a matter of fact, in preliminary attempts, we found out that Ugi reactions employing free para-hydroxybenzylamines proceed in very poor yields (<25%), probably

• because of interference of the phenol moiety, which can act as internal nucleophile. For these reasons we decided to use the O-benzylated benzylamines as starting materials for the U-4CR, postponing the hydrogenolytic removal of the protecting group after the condensation. Four different benzyl azides 2a

Less reactive dipoles of diazodicarbonyl compounds in reaction with cycloaliphatic thioketones – First evidence for the 1,3-oxathiole–thiocarbonyl ylide interconversion

• Valerij A. Nikolaev,
• Alexey V. Ivanov,
• Ludmila L. Rodina and
• Grzegorz Mlostoń

Beilstein J. Org. Chem. 2013, 9, 2751–2761, doi:10.3762/bjoc.9.309

• prepared from the corresponding 1,3-dicarbonyl compounds and arenesulfonyl azides by diazo-transfer reactions [18]. Thioketones 1a,b were prepared from the corresponding ketones by known procedures [15][16]. General procedure for the reaction of diazodicarbonyl compounds with thioketone 1a: A mixture of

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• . It is supposed that bromide ions can bind strongly to copper(I) centres in organic media, but due to a tight layer of solvent molecules they cannot do so in aqueous solution. Thus, the CuAAC reaction with in situ generated azides could only be carried out in water as reaction medium. {The detrimental

• this byproduct can be prevented by using copper(I) bromide instead of the iodide salt. This reactivity of 1-haloalkynes is in accordance with the observation that 5-iodo-1,2,3-triazoles are formed as byproducts, when CuI is used as catalyst in CuAAC reactions of azides and terminal alkynes as has been

• , exchange of the halide group when 1-bromoalkynes are reacted with azides in the presence of copper(I) iodide [155] as observed by Rutjes et al. cannot be explained by this pathway. In 2006, the group of Nolan presented the synthesis of 1,4,5-trisubstituted-1,2,3-triazoles by cycloaddition reactions between

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• pleased to discover that the oxidative azidation [36] allowed a direct access to the corresponding α-azidofuranones in one step. The two diastereomers of the azides were obtained in a 60:40 ratio. The subsequent reduction of the carbonyl group with L-selectride in THF furnished the α

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• urea derivatives. A small set of five different primary and secondary alkyl and benzyl azides were synthesized. Besides the azido derivatives synthesized from 17–19, the two volatile azides synthesized from 20 and 21 (n-butyl and allyl azide, respectively) were obtained under N2 pressure. After

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• light-mediated reductions such as reductive dehalogenation [47][48][49][50][51], reductive radical cyclization [52][53][54], reduction of activated ketones [49], and reduction of aromatic azides [55]. The third mode involves deprotonation of amine radical cation 2 to form α-amino radical 3, which is

Synthesis of mucin-type O-glycan probes as aminopropyl glycosides

• David Benito-Alifonso,
• Rachel A. Jones,
• Anh-Tuan Tran,
• Hannah Woodward,
• Nichola Smith and
• M. Carmen Galan

Beilstein J. Org. Chem. 2013, 9, 1867–1872, doi:10.3762/bjoc.9.218

• susceptible to reduction, such as azides. After aqueous workup, the crude materials were subjected to removal of the acetyl groups using sodium hydroxide in methanol (pH = 11) followed by concomitant acetal hydrolysis and azide reduction using hydrogen and palladium on charcoal (Pd/C) in methanolic HCl (5

[3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

• Stephan Cludius-Brandt,
• Lukas Kupracz and
• Andreas Kirschning

Beilstein J. Org. Chem. 2013, 9, 1745–1750, doi:10.3762/bjoc.9.201

• Stephan Cludius-Brandt Lukas Kupracz Andreas Kirschning Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1b, 30167 Hannover, Germany 10.3762/bjoc.9.201 Abstract The photodenitrogenation of vinyl azides to 2H-azirines by using a photoflow reactor is reported and compared

• from the corresponding vinyl azide. Keywords: azirines; cycloaddition; flow chemistry; flow reactors; inductive heating; nitrile ylides; photochemistry; vinyl azides; Introduction Recently, photochemistry has seen a renaissance despite the fact that under batch conditions specialized reaction vessels

• photoinduced activation of vinyl azides 1, which gives rise to 2H-azirines 2 via vinyl nitrenes after the loss of molecular nitrogen and subsequent ring-opening under photochemical conditions to provide the nitrile ylides 3 (Scheme 1). For recent examples for the use of azirines in organic syntheses please

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• , the reaction temperature was lowered to room temperature by the joint use of both basic and acidic additives to improve the safety of the synthesis, as azides were to be handled as unstable reactants. Scale-up experiments were also performed, which led to the achievement of gram-scale production in a

• applications in numerous other areas of modern chemical sciences, such as bioconjugation [13], supramolecular chemistry, [14] and polymer sciences [15]. Probably the most useful and powerful procedure for the synthesis of 1,2,3-triazoles is the Huisgen 1,3-dipolar cycloaddition of organic azides with

• bioactive agents with anticancer, antibacterial, antiviral or analgesic effects (Figure 2) [25][26]. The alicyclic β-amino acids are key intermediates for the synthesis of a series of pharmaceutically relevant products [27], such as amino esters, amino alcohols, azides and heterocycles. Moreover, they are

A construction of 4,4-spirocyclic γ-lactams by tandem radical cyclization with carbon monoxide

• Mitsuhiro Ueda,
• Yoshitaka Uenoyama,
• Nozomi Terasoma,
• Shoko Doi,
• Shoji Kobayashi,
• Ilhyong Ryu and
• John A. Murphy

Beilstein J. Org. Chem. 2013, 9, 1340–1345, doi:10.3762/bjoc.9.151

• azides with CO was achieved. The reaction of iodoaryl allyl azides, TTMSS and AIBN under CO pressure (80 atm) in THF at 80 °C gave the desired 4,4-spirocyclic indoline, benzofuran, and oxindole γ-lactams in moderate to good yields. Keywords: 4,4-spirocyclic indol γ-lactams; carbon monoxide; free radical

• ; iodoaryl allyl azides; tandem radical cyclization; Introduction 4,4-Spirocyclic oxindole γ-lactams containing a quaternary carbon center are key structures for the synthesis of biologically active natural products and the related analogues [1][2][3][4]. Therefore, the development of an efficient synthesis

• tandem reaction of iodoaryl alkenyl azides under radical conditions (Scheme 1) [13][14]. Curran et al. reported the synthesis of spirocyclic pyrrolidinyl dihydroquinolinones by tandem radical cyclization [15][16]. In this study we report a radical cyclization/annulation approach to 4.4-spirocyclic γ

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