Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• NCS and NBS are able to convert the silane into a reactive species. However, the yields were low in all cases. Changing the bromination reagent to elemental bromine significantly improved the yields (Table 1, entries 4 and 5) [36]. Diethyl ether proved to be important as a solvent, the change to THF

• led to a total decomposition – most probably due to ring-opening reactions with bromosilanes [37]. Further, we investigated the influence of the amount of bromine on the reaction and concluded that stoichiometric quantities entirely fulfill the demands of the bromination (Table 1, entries 7 and 8

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• ]. The synthesis commenced with the preparation of the isoindolinone building block 134. Friedel–Crafts acetylation of 132, followed by a Lieben haloform degradation gave the corresponding acid, which after methylation yielded 133. Bromination and lactam formation afforded isoindolinone 134. The

• in the total synthesis of 193 by Schmalz (Scheme 24) [149]. Reaction of lithiated 188 (three steps from commercially available 5-methylresorcinol) with the aldehyde 189 (double bromination of 3,5-dimethoxybenzaldehyde) gave the racemic alcohol 190. Oxidation to the benzophenone, installation of the

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• stereospecifically the corresponding piperidone 4 in 80% yield. Subsequent bromination with CBr4 in the presence of PPh3 (Appel reaction) gave 5 in 84% yield. Finally, deprotection with 1 M SnCl4 in dichloromethane then neutralization by using K2CO3 afforded the final product (−)-epimyritine in a 80% yield. N-Cbz

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• auxiliary removal gave the N-Boc protected L-amino acid 7 (L-5-F3Ile). Likewise, the corresponding D-amino acid 10 (D-5-F3-allo-Ile) was prepared by α-bromination followed by nucleophilic azide displacement under stereochemical inversion (Scheme 2). The absolute configuration of the amino acids was

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

• Kimberley A. Roper,
• Malcolm B. Berry and
• Steven V. Ley

Beilstein J. Org. Chem. 2013, 9, 1781–1790, doi:10.3762/bjoc.9.207

• possible to perform the Appel reaction using the same monolith and the relationship between the mechanisms of the two reactions is discussed. Keywords: bromination; flow chemistry; Ramirez gem-dibromoolefination reaction; solid-supported reagent; triphenylphosphine monolith; Introduction The advantages

• monolith, leaving the product bound to the polymer. Interestingly the batch bromination of 3-phenylpropiolaldehyde (Table 1, entry 7) requires the addition of 2.5 equivalents of 2,6-lutidine [60], however pleasingly, this was not required when the substrate was brominated using the flow procedure. It was

The preparation of several 1,2,3,4,5-functionalized cyclopentane derivatives

• André S. Kelch,
• Peter G. Jones,
• Ina Dix and
• Henning Hopf

Beilstein J. Org. Chem. 2013, 9, 1705–1712, doi:10.3762/bjoc.9.195

• . In principle these should be convertible by elimination reactions to the desired target molecule. Keywords: bromination; cyclopentanes; esterification; permethylcyclopentadiene; polyfunctional compounds; radialenes; Introduction Radialenes are cyclic cross-conjugated hydrocarbons that consist

• with various bromination reagents. Whenever possible we confirm the structures of intermediate compounds or byproducts by X-ray structural analysis. Results and Discussion cis,cis,cis,cis-1,2,3,4,5-Pentakis(hydroxymethyl)cyclopentane (16) and derivatives The pentaalcohol 16 is a known compound, having

• = 60.0, 63.2, and 65.5 ppm. The signals of the minor isomer(s) can hardly be differentiated from the noise. The bromination of 30 proceeded with varying results; most of the methods that were unsuccessfully used above in the case of 16 also fail for its isomer (HBr, PBr3, SOBr2 in different halogenated

Bromination of hydrocarbons with CBr₄, initiated by light-emitting diode irradiation

• Yuta Nishina,
• Bunsho Ohtani and
• Kotaro Kikushima

Beilstein J. Org. Chem. 2013, 9, 1663–1667, doi:10.3762/bjoc.9.190

• Yuta Nishina Bunsho Ohtani Kotaro Kikushima Research Core for Interdisciplinary Science, Okayama University, Tsushimanaka, Kita-ku, Okayama 700-8530, Japan Catalysis Research Center, Hokkaido University, Sapporo 001-0021, Japan 10.3762/bjoc.9.190 Abstract The bromination of hydrocarbons with CBr4

• species for the bromination. The generation of CHBr3 was confirmed by NMR spectroscopy and GC–MS spectrometry analysis, indicating that the present bromination involves the homolytic cleavage of a C–Br bond in CBr4 followed by radical abstraction of a hydrogen atom from a hydrocarbon. Keywords

• : bromination; free radical; hydrocarbon; light-emitting diode; photo irradiation; Introduction Bromination reactions of organic compounds are fundamental reactions for providing a wide variety of organic precursors for industrial materials [1][2][3][4][5][6][7][8]. Generally, the bromination of saturated

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• the halogenation of diazoacetamides. We report herein the bromination of the diazoacetamides derived from a selection of cyclic secondary amines, using DBU and N-bromophthalimide (NBP), as well as an investigation of the ability of the carbenes/carbenoids derived from the resulting α

• yields. Preparation of the diazoacetamides. Bromination of the diazoacetamides 3a–f and thermolysis of the α-bromodiazoacetamides 4a–f. Yieldsa of β-lactams 5a–f obtained by thermolysis of α-bromodiazoacetamides 4a–f. Supporting Information Supporting Information File 66: Detailed experimental

Incorporation of perfluorohexyl-functionalised thiophenes into oligofluorene-truxenes: synthesis and physical properties

• Neil Thomson,
• Alexander L. Kanibolotsky,
• Joseph Cameron,
• Tell Tuttle,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2013, 9, 1243–1251, doi:10.3762/bjoc.9.141

• -iodo-4-perfluorohexylthiophene, which was separated by column chromatography. Compound 4 then underwent Suzuki–Miyaura coupling with compound 5, which was synthesised according to our previously published method [17], and the product obtained, 6, was deprotected by bromination to give compound 7 and

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• ethyl xanthate in ethanol under reflux. Bromination of 1 led to the key intermediate 2-bromo-5,6-dimethylbenzimidazole (2), which reacted smoothly with 3-aminopropanol to give the amine 3 in high yield and purity after extraction. The solvent-free microwave process employed was superior to traditional

Reactions of salicylaldehyde and enolates or their equivalents: versatile synthetic routes to chromane derivatives

• Ishmael B. Masesane and
• Zelalem Yibralign Desta

Beilstein J. Org. Chem. 2012, 8, 2166–2175, doi:10.3762/bjoc.8.244

• corresponding 2-aminochromene derivatives 22 and 37 in 92 and 82% yields respectively (Scheme 13) [26]. It is instructive to note that TBBDA is a versatile reagent in organic synthesis and has been reported to be efficient in oxidation of primary and secondary alcohols [27], in bromination of aromatic compounds

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

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Iridium-catalyzed intramolecular [4 + 2] cycloadditions of alkynyl halides

• Andrew Tigchelaar and
• William Tam

Beilstein J. Org. Chem. 2012, 8, 1765–1770, doi:10.3762/bjoc.8.201

• ). Deprotonation of 8 with sodium hydride, followed by trapping with propargyl bromide provided 9 in 60% yield, and a Mitsunobu reaction between 8 and sulfonamide 10 (prepared as per reference [47]) provided 11 in 74% yield. Bromination of 9 and 11 provided diene-tethered alkynyl halides 1c (57%) and 1e (83

• bromination conditions to provide 1g in 77% yield. Compounds 1a–1g were then subjected to the optimized cycloaddition conditions (Table 3). In general, the Ir-catalyzed [4 + 2] cycloadditions occurred smoothly for all substrates, forming bicyclic products 2 in good yield (75–94%) (Table 3), and in each case a

trans-2-(2,5-Dimethoxy-4-iodophenyl)cyclopropylamine and trans-2-(2,5-dimethoxy-4-bromophenyl)cyclopropylamine as potent agonists for the 5-HT₂ receptor family

• Adam Pigott,
• Stewart Frescas,
• John D. McCorvy,
• Xi-Ping Huang,
• Bryan L. Roth and
• David E. Nichols

Beilstein J. Org. Chem. 2012, 8, 1705–1709, doi:10.3762/bjoc.8.194

• precursor and subsequent bromination to provide both enantiomers of 5. Results and Discussion Racemic 4 and 5 were compared in radioligand competition assays against radiolabeled antagonists defined at the human 5-HT2A and 5-HT2C receptors and compared with racemic 1a and 1b. The results are shown in Table

• ester 7 followed by bromination of acid 9 using Br2-dioxane complex gave a good yield of bromo acid 10b. These acids were readily converted to their isocyanates using the Weinstock modification of the Curtius rearrangement [6]. Those isocyanates were heated with tert-butanol to afford the corresponding

• bromo compound 5 appeared somewhat more stable. We then followed a more efficient divergent approach to obtain the enantiomers of 5 that employed resolution of the cyclopropane carboxylic acid, followed by bromination, and then conversion to the cyclopropylamine (Scheme 3). We are aware that the use of

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part I: Dihydronepetalactones

• Nicole Zimmermann,
• Robert Hilgraf,
• Lutz Lehmann,
• Daniel Ibarra and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1246–1255, doi:10.3762/bjoc.8.140

• -pulegenic acid 10 via bromination, Favorskii rearrangement, and subsequent elimination (Scheme 1). Stereoselective addition of hydrochloric acid afforded the chloride 11, and subsequent elimination of hydrochloric acid gave a mixture of the methyl esters 12 and 13 (methyl trans-pulegenate) [20][21][22

On the bromination of the dihydroazulene/vinylheptafulvene photo-/thermoswitch

• Virginia Mazzanti,
• Martina Cacciarini,
• Søren L. Broman,
• Christian R. Parker,
• Magnus Schau-Magnussen,
• Andrew D. Bond and
• Mogens B. Nielsen

Beilstein J. Org. Chem. 2012, 8, 958–966, doi:10.3762/bjoc.8.108

• dihydroazulene (DHA)/vinylheptafulvene (VHF) system (with two cyano groups at C1) functions as a photo-/thermoswitch. Direct ionic bromination of DHA has previously furnished a regioselective route to a 7,8-dibromide, which by elimination was converted to a 7-bromo-substituted DHA. This compound has served as a

• central building block for functionalization of the DHA by palladium-catalyzed cross-coupling reactions. The current work explores another bromination protocol for achieving the isomeric 3-bromo-DHA and also explores the outcome of additional bromination of this compound as well as of the known 7-bromo

• -DHA. Results: Radical bromination on two different VHFs by using N-bromosuccinimide/benzoyl peroxide and light, followed by a ring-closure reaction generated the corresponding 3-bromo-DHAs, as confirmed in one case by X-ray crystallography. According to a 1H NMR spectroscopic study, the ring closure

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• . Bromination in the core with dibromocyanuric acid (31) afforded an intractable mixture containing the 2,6-dibromo NDA 32 together with lower and higher homologues [16]. However, pure product 33 could be readily isolated from this mixture after transformation of the NDAs into the core-substituted

meta-Oligoazobiphenyls – synthesis via site-selective Mills reaction and photochemical properties

• Raphael Reuter and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2012, 8, 877–883, doi:10.3762/bjoc.8.99

• ) was oxidized with potassium permanganate in a 1:1 solvent mixture of pyridine/H2O, to the corresponding benzoic acid 5. The reaction proceeded with an acceptable yield of 66%. However, the resulting highly deactivated aromatic system 5 did not react even under harsh bromination conditions with NBS in

• concentrated sulfuric acid. Therefore, the reaction sequence was changed to bromination first, followed then by oxidation of the benzylic position. The bromination proceeded slowly, and after three days of stirring at 50 °C, only 53% of 2-nitro-4-tert-butyl-6-bromotoluene (7) was obtained. It turned out that

Regioselective chlorination and bromination of unprotected anilines under mild conditions using copper halides in ionic liquids

• Han Wang,
• Kun Wen,
• Nurbiya Nurahmat,
• Yan Shao,
• He Zhang,
• Chao Wei,
• Ya Li,
• Yongjia Shen and
• Zhihua Sun

Beilstein J. Org. Chem. 2012, 8, 744–748, doi:10.3762/bjoc.8.84

• Science, Shanghai, 201620, China 10.3762/bjoc.8.84 Abstract By using ionic liquids as solvents, the chlorination or bromination of unprotected anilines at the para-position can be achieved in high yields with copper halides under mild conditions, without the need for potentially hazardous operations such

• as supplementing oxygen or gaseous HCl. Keywords: halogenation; ionic liquids; oxydation; regioselectivity; solvent effects; Introduction Chlorination and bromination of aromatic rings are classical and widely performed transformations, which are useful in many multistep organic-synthesis

• procedures. Regioselectivity with electron-rich substrates such as aniline will predominantly produce para- and ortho-substitutions. However, chlorination or bromination of aniline derivatives is often performed with protected anilines. This increases both the cost of synthesis and the environmental impact

Synthesis of 2,6-disubstituted tetrahydroazulene derivatives

• Zakir Hussain,
• Henning Hopf,
• Khurshid Ayub and
• S. Holger Eichhorn

Beilstein J. Org. Chem. 2012, 8, 693–698, doi:10.3762/bjoc.8.77

• isomer. Formation of one major isomer under the given conditions could be explained through the hydrogen shifts of cycloheptatrienes by the so-called Berson–Willcott rearrangement [21]. We assume that bromination (Br2) and dehydrobromination (Et3N) of 4 resulted in the formation of an intermediate, which

Discovery of practical production processes for arylsulfur pentafluorides and their higher homologues, bis- and tris(sulfur pentafluorides): Beginning of a new era of “super-trifluoromethyl” arene chemistry and its industry

• Teruo Umemoto,
• Lloyd M. Garrick and
• Norimichi Saito

Beilstein J. Org. Chem. 2012, 8, 461–471, doi:10.3762/bjoc.8.53

• gaseous SF5Cl with acetylene, followed by bromination, dehydrobromination, and reduction with zinc, giving pentafluorosulfanylacetylene (HC≡CSF5), which was then reacted with butadiene, followed by an aromatization reaction at very high temperature, gave phenylsulfur pentafluoride [35]. Recently

Synthesis and mesomorphic properties of calamitic malonates and cyanoacetates tethered to 4-cyanobiphenyls

• Katharina C. Kress,
• Martin Kaller,
• Kirill V. Axenov,
• Stefan Tussetschläger and
• Sabine Laschat

Beilstein J. Org. Chem. 2012, 8, 371–378, doi:10.3762/bjoc.8.40

• . Starting from the corresponding diols 6a,b, 6-bromohexan-1-ol (7a) and 10-bromodecan-1-ol (7b) were obtained in moderate yields by bromination with aqueous HBr in toluene [35]. The bromides 7a,b were reacted with 4-cyano-1,1'-biphenol (8) in acetone in the presence of K2CO3 giving compounds 9a,b, bearing

Organic synthesis using (diacetoxyiodo)benzene (DIB): Unexpected and novel oxidation of 3-oxo-butanamides to 2,2-dihalo-N-phenylacetamides

• Wei-Bing Liu,
• Cui Chen,
• Qing Zhang and
• Zhi-Bo Zhu

Beilstein J. Org. Chem. 2012, 8, 344–348, doi:10.3762/bjoc.8.38

• (Scheme 2). To the best of our knowledge, there are several reports on chlorination and bromination reactions with PhI(OAc)2 and a halogen source such as TMSBr, lithium halide or pyridinium halide [32][33][34]. Also, there are several reports on the synthesis of difunctionalized acetamide derivatives [35