Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• ) and irradiation of the ligand–protein complex to form an excited intermediate, which eventually leads to a covalently crosslinked ligand–receptor conjugate, which has to be identified by mass spectrometry (Figure 1). Three widely used photoreactive groups are aryl azides, benzophenones and diazirines

Efficient catenane synthesis by cucurbit[6]uril-mediated azide–alkyne cycloaddition

• Antony Wing Hung Ng,
• Chi-Chung Yee,
• Kai Wang and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2018, 14, 1846–1853, doi:10.3762/bjoc.14.158

• macrocycles will be ensured. One example is the use of an active metal template, in which the macrocyclization is mediated by the metal ion inside the cavity of a metal-coordinating macrocycle [20]. Cucurbit[6]uril (CB[6]) has also been demonstrated to bind to ammonium-containing azides and alkynes and to

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• , alcohols, thiols, and azides as the nucleophiles [53]. The Eu3+ and Tb3+ versions were prepared by metal exchange in methanol, between the cobalt complex 67 and the triflate salts of the rare earths, giving the desired complexes CP1 and CP2 in 83% and 86% yield, respectively. The solvent free thiolysis of

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• , in combination with the Ph3P-DEAD system, leaves the acid-labile protecting groups of 127 intact, other than when HF is used. Zbiral’s group on the other hand, developed the synthesis of glycosyl azides such as 128 in a Mitsunobu procedure with 127, using hydrazoic acid as the azide source (Scheme 27

• carbohydrates with an alkoxyamine bond [114]. Synthesis of glycosyl fluorides and glycosyl azides according to Mitsunobu [118][119]. Anomeric oxidation under Mitsunobu conditions [122].

[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

• , in deuteric solvent hydrolyzed to give 3-deutero pyrazole. However, Fokin et al. has recently [123] revealed that monomeric copper acetylide complexes are not reactive toward organic azides in analogous copper-catalyzed alkyne–azide cycloaddition (CuAAC) and the catalysis by an external Cu(I) salt is

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• ], glycoconjugates [30][31][32], N-glycosyl heterocycles [33][34], N-glycosyl triazole [35][36], etc. Glycosyl azides can be accessed from the corresponding glycosyl halides [37][38][39][40] by nucleophilic displacement with NaN3 or using trimethylsilyl azide in the presence of a phase transfer catalyst [41][42][43

• ][44][45]. More commonly, glycosyl azides are synthesized from per-O-acetylated sugars using trimethylsilyl azide in the presence of a variety of Lewis acids such as SnCl4 [46], TiCl4 [47][48], BF3·OEt2 [49], TMSOTf [50][51], etc. However, at higher concentration Lewis acids can potentially lead to

• slow anomerization [52]. In 2011, Chen’s group reported that 5 mol % FeCl3 can catalyze the reaction of trimethylsilyl azide with per-O-acetylated β-monosaccharides to afford glycosyl azides in 3–7 h, whereas per-O-acetylated β-di- and trisaccharides required 22–28 h for complete conversion [53

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

• , Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil 22941-909, Research Center Pharmaceutical Engineering GmbH (RCPE), Inffeldgasse 13, 8010 Graz, Austria 10.3762/bjoc.14.36 Abstract An efficient three-step protocol was developed to produce 2-(azidomethyl)oxazoles from vinyl azides in a

• continuous-flow process. The general synthetic strategy involves a thermolysis of vinyl azides to generate azirines, which react with bromoacetyl bromide to provide 2-(bromomethyl)oxazoles. The latter compounds are versatile building blocks for nucleophilic displacement reactions as demonstrated by their

• integration; vinyl azides; Introduction Oxazoles are an important class of five-membered aromatic heterocycles containing one oxygen and one nitrogen atom in their structures. The oxazole moiety is relatively stable and is found widely in nature [1][2][3]. Naturally occurring oxazoles include compounds with

Carbohydrate inhibitors of cholera toxin

• Vajinder Kumar and
• W. Bruce Turnbull

Beilstein J. Org. Chem. 2018, 14, 484–498, doi:10.3762/bjoc.14.34

• toxin lectins [72]. Gibson and co-workers made a series of polyacrylates bearing pentafluorophenyl active ester groups which could be subsequently converted to polyacrylamides by reaction with amine linkers of varying lengths [71]. The attachment of galactosyl azides provided a series of glycopolymer

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

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• high background. The masking of fluorophores by a more stable group, such as azides, is more attractive. Unfortunately, the phosphine probe generally required for the unmasking of the azide probe is susceptible to rapid aerobic oxidation. Accordingly, new developments in this area are still required

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• -methacryloylbenzamides is similar and includes alkyl substituents on the nitrogen atom and electron-rich and poor aromatic moieties. Mao and Zhou applied vinyl azides for the radical cross-coupling with sodium sulfinate salts (Scheme 56) [95]. They observed that the azide moiety decomposes during the reaction (loss of

• N2) which triggers an intramolecular cyclization reaction via a nitrogen-centred radical intermediate to form sulfonylated phenanthridines. The reaction is photocatalyzed by [Ru(bpy)3]Cl2 under irradiation with blue LEDs and proceeds smoothly for a variety of substituted vinyl azides and sulfonyl

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

• ]. Following the work of Fleming et al., several groups have investigated the use of different conditions to try and increase the efficiency of the NCAAC on the surface of AuNPs. Limapichat et al. used other electron deficient alkynes (7–11) as substrates for the NCAAC, and observed that 75% of the azides on

• conversion of the azides to triazoles. However, significant particle decomposition and/or aggregation were observed when the AuNPs were heated for more than 15 minutes in the microwave reactor. Astruc and co-workers reported several modifications to try and increase the efficiency of CuAAC reactions of AuNPs

• system was then used for the detection of amyloid-β peptides [74], whose aggregation is responsible for Alzheimer’s disease [75]. In 2014, Fairbanks and co-workers reported a one-pot aqueous compatible method for making various triazole-linked glycoconjugates via intermediate glycosyl azides, which then

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• N7-position or a combination of both. (A) Functional moieties such as alkynes and azides can be enzymatically transferred to the N2-position using GlaTgs-Var. or N7-position using Ecm1 [88][89][90][91]. While transfer efficiencies decrease with increasing sterical demand when using GlaTgs-Var

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• using 18O2; no reaction occurred under N2 instead of O2; K2S2O8 rather than O2 served as initiator; the radical CF3SO2• could either extrude SO2 to CF3• or react with O2 to re-initiate the radical chain process (Scheme 7). Vinyl azides were used by Liu and co-workers as precursors of α

• -trifluoromethylated ketones by reaction of CF3SO2Na under photoredox catalysis. The substrate scope was broad and the reaction proceeded with high functional group tolerance; indeed, aryl-, alkyl-, hetero-functionalised terminal as well as non-terminal vinyl azides 15 were compatible with the reaction conditions. In

A concise flow synthesis of indole-3-carboxylic ester and its derivatisation to an auxin mimic

• Marcus Baumann,
• Ian R. Baxendale and
• Fabien Deplante

Beilstein J. Org. Chem. 2017, 13, 2549–2560, doi:10.3762/bjoc.13.251

• new entries into these valuable structures [6]. However, common to the majority of these indole syntheses is the use of hazardous entities such as hydrazines (Fischer), diazonium species (Japp–Klingemann) or azides (Hemetsberger–Knittel) or the necessity to construct specifically functionalised

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• intriguing versatility as building blocks in organic and medicinal chemistry, as their reactivity is unique. Their chemistry involves several highly selective reactions, e.g., [3 + 2] cycloadditions with azides and isoelectronic functional groups (among them the copper or ruthenium-catalyzed azide–alkyne

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• reaction conditions and short reaction times, the advantage of CuAAC is the formation of 1,2,3-triazoles-1,4-disubstituted in a highly regioselective manner [41]. Recently, Cornec et al. [44] synthesized 4,6-dimethyl-2-(4-aryl-1H-1,2,3-triazol-1-yl)pyrimidines from azides using copper salts. The reaction

• solution (CDCl3 and DMSO-d6), while azide species 7a–h were observed in the solid state. Notwithstanding, although only the tetrazoles were observed for compounds 6a–c in solution, the conditions at which the compounds were introduced can induce the equilibrium to favor the presence of the azides (e.g

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

• states for the mechanochemical CuAAC reaction of target quinoline derivatives and p-substituted phenyl azides. We have also investigated the effect of the p-substituent in the azide on the reaction progress and yields. Direct monitoring by in situ Raman spectroscopy was used to gain an insight into the

• methine C-3 protons displayed in a 1H,1H-NOESY spectrum of 4 (Figure S10 in Supporting Information File 1). Compound 4 was then submitted to Cu(I)-catalyzed 1,3-dipolar cycloaddition with selected halogen-substituted and non-substituted aromatic azides to yield target N-heterocyclic hybrids 5–8 containing

• raised by application of method 1a* for the p-chloro- (from 21 to 77%, Table 1, entry 1) and p-bromophenyl azides (from 45 to 76%, Table 1, entry 2). On the other hand, the reaction with the non-substituted azide in all solution procedures, even by method 1a*, gave compound 8 in low yield (5–21%, Table 1

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

• the metal catalyst from rhodium to iridium. In 2016, using an Ir(III) catalyst an unprecedented ortho-selective Csp2–H bond amidation of benzamides with sulfonyl azides as the amide source was done under solvent-free ball mill conditions (Scheme 51) [183]. They could also isolate cyclic iridium

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

• transglycosylations are available in a review by Nogushi, et al. [70]. 4.1.2 Synthesis of glycosyl azides, dithiocarbamates, and thiols: Shoda and colleagues have also shown that when using similar conditions to those described above in the presence of certain nucleophiles glycosyl azides [73], dithiocarbamates [74

• conditions were feasible for the synthesis of glycosyl azides which are highly useful precursors for N-linked glycans [95] or Cu-catalyzed cycloadditions with alkynes (as shown above) [85]. By using tetrabutylammonium chloride and an amine base the highly reactive chlorinated intermediate forms that can be

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• issues owing to many potential side reactions, particularly in relation to chemoselectivity, i.e., over-hydrogenation of alkenes to alkanes [44][45], resistance of other functional groups (ketones [46][47], amines [48][49], azides [50]), regioselectivity [51][52] , isomerization [53][54] and

Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanyl)phenyl-1H-1,2,3-triazol-4-yl)ketones

• Gabriel P. Costa,
• Natália Seus,
• Juliano A. Roehrs,
• Raquel G. Jacob,
• Ricardo F. Schumacher,
• Thiago Barcellos,
• Rafael Luque and
• Diego Alves

Beilstein J. Org. Chem. 2017, 13, 694–702, doi:10.3762/bjoc.13.68

• most attractive way for their preparation is the thermal 1,3-dipolar cycloaddition of alkynes and azides, introduced by Huisgen which usually gives rise to a mixture of 1,4 and 1,5-isomers [16][17][18][19]. More recently, transition metal catalysts based on copper, ruthenium, silver and iridium salts

• carbonyl compounds could successfully generate an enamine or an enolate, and these species react as dipolarophiles with organic azides in organocatalyzed 1,3-dipolar cycloadditions. Our research group has demonstrated β-enamine–azide cycloaddition reactions for the synthesis of selenium-functionalized

• -amides with a range of substituted aryl azides providing and efficient access to new N-aryl-1,2,3-triazoyl carboxamides in good to excellent yields and short reaction times of [75]. However, to the best of our knowledge, the use of sonochemistry to synthesize complex selenium-functionalized 1,2,3

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• -deficient alkene led to the intermediate bromoisoxazoline from which, by loss of HBr, a 3,5-disubstituted isoxazole derivative is formed as major regioisomer [34]. Based on the copper(I)-catalyzed click reactions of organic azides with terminal acetylenes [35], different copper(I)-catalyzed synthetic

Pd- and Cu-catalyzed approaches in the syntheses of new cholane aminoanthraquinone pincer-like ligands

• Nikolay V. Lukashev,
• Gennadii A. Grabovyi,
• Dmitry A. Erzunov,
• Alexey V. Kazantsev,
• Gennadij V. Latyshev,
• Alexei D. Averin and
• Irina P. Beletskaya.

Beilstein J. Org. Chem. 2017, 13, 564–570, doi:10.3762/bjoc.13.55

• -catalyzed reactions were applied for the modification of bile acids – cross-coupling [28][29] (Scheme 1) and Cu(I)-catalyzed cycloaddition of azides to alkynes (Figure 1) [11][16][30][31][32]. We developed [33][34][35] a convenient technique for the synthesis of bile acids containing dimeric compounds and

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• " for safety reasons, such as those involving diazo compounds, hydrazine, azides, phosgene, cyanides and other hazardous chemicals could be performed with relatively low risk using flow technology [72][73][74][75][76]. Several research groups investigated this aspect, as highlighted by several available