A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• δ-position silenced, presented a completely straightforward precursor to 1 and proved to be amenable to coupling with 4 under various reaction conditions. Briefly [14], 8 was prepared from levulinic acid (5) through δ-bromination and concomitant methyl ester formation (compound 6), followed by

Photorelease of phosphates: Mild methods for protecting phosphate derivatives

• Sanjeewa N. Senadheera,
• Abraham L. Yousef and
• Richard S. Givens

Beilstein J. Org. Chem. 2014, 10, 2038–2054, doi:10.3762/bjoc.10.212

• -Bromination with copper(II) bromide [20] gave 8 (96%, direct bromination of 6 gave poor yields). The TBS group was removed in 30% aqueous methanol containing 10–20% methylene chloride and several molar equivalents of potassium hydrogen sulfate to provide hydroxy bromo ketone 9 (yield, 75%) [21], which was

• with Friedel–Crafts acylation of 1-methoxynaphthalene (11) yielding 1-acetyl-4-methoxynaphthalene (12, 73%). α-Bromination with copper(II) bromide gave 13 (44%) which was converted to the phosphate ester using tetramethylammonium diethyl phosphate in dimethoxyethane (DME) at room temperature to give

• α-bromination to 17 (89%). TBS deprotection gave 2-bromo-1-(4-hydroxy-1-naphthyl)ethanone, (18, 59%) which was converted to diethyl (2-(4-hydroxynaphthalen-1-yl)-2-oxoethyl) phosphate (1,4-HNA DEP, 14a, 31%) with tetramethylammonium diethyl phosphate. Benzyl protected diethyl 2-(8-hydroxyquinolin-5

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• work-up and reversed-phase column chromatography (C18) (Scheme 2) [14]. Then, the α-bromo aldehyde 7 was obtained in two steps from commercially available 3-phthalimidopropan-1-ol that was oxidized using Dess–Martin periodinane. Subsequent in situ bromination of the 3-phthalimidopropan-1-al with

Rasta resin–triphenylphosphine oxides and their use as recyclable heterogeneous reagent precursors in halogenation reactions

• Xuanshu Xia and
• Patrick H. Toy

Beilstein J. Org. Chem. 2014, 10, 1397–1405, doi:10.3762/bjoc.10.143

• reactions discussed above, some of these reactions did not proceed to completion, even when the reaction time was lengthened. Generally, it was observed that the bromination reactions afforded higher product yields than did the corresponding chlorination reactions (Table 2, entries 1–8), except when

Stereoselective synthesis of carbocyclic analogues of the nucleoside Q precursor (PreQ₀)

• Sabin Llona-Minguez and
• Simon P. Mackay

Beilstein J. Org. Chem. 2014, 10, 1333–1338, doi:10.3762/bjoc.10.135

• diastereospecific available [30] (Figure 4). The process started with a Wohl–Ziegler allylic bromination of cyclopentene. The volatile and unstable allylic halide 10 was immediately reacted with excess N,N-dibenzylamine and the resulting allylic amine 11 was obtained in good yield over two steps. Next, we

Site-selective covalent functionalization at interior carbon atoms and on the rim of circumtrindene, a C₃₆H₁₂ open geodesic polyarene

• Hee Yeon Cho,
• Ronald B. M. Ansems and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2014, 10, 956–968, doi:10.3762/bjoc.10.94

• circumtrindene might also be brominated. Fullerenes are known to undergo bromine addition with elemental bromine in chlorinated solvents at room temperature [28]. To avoid the unwanted bromination at interior carbon atoms, the reaction conditions were carefully optimized (see Supporting Information File 1 for

Nonanebis(peroxoic acid): a stable peracid for oxidative bromination of aminoanthracene-9,10-dione

• Vilas Venunath Patil and
• Ganapati Subray Shankarling

Beilstein J. Org. Chem. 2014, 10, 921–928, doi:10.3762/bjoc.10.90

• Vilas Venunath Patil Ganapati Subray Shankarling Department of Dyestuff Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai - 400019, India. Tel.: 91-22-33612708, Fax: 91-22-33611020 10.3762/bjoc.10.90 Abstract A new protocol for the oxidative bromination of aminoanthracene

• protocol has a broad scope for the bromination of various substituted and unsubstituted aminoanthracene-9,10-diones. Keywords: aminoanthracene-9,10-dione; benzanthrone; KBr; nonanebis(peroxoic acid); oxidative bromination; Introduction The brominated aminoanthracene-9,10-dione derivatives and

• benzanthrone are widely used as intermediates for pharmaceuticals [1][2][3], for medicinal applications [4], as dyes [5][6][7][8][9] and in Hg2+ ion sensors [10]. Although these bromo derivatives have a wide range of applications, it is difficult to carry out their bromination as the two carbonyl groups of

Visible-light photoredox catalysis enabled bromination of phenols and alkenes

• Yating Zhao,
• Zhe Li,
• Chao Yang,
• Run Lin and
• Wujiong Xia

Beilstein J. Org. Chem. 2014, 10, 622–627, doi:10.3762/bjoc.10.53

• Yating Zhao Zhe Li Chao Yang Run Lin Wujiong Xia State Key Lab of Urban Water Resource and Environment, The Academy of Fundamental and Interdisciplinary Sciences, Harbin Institute of Technology, Harbin 150080, China 10.3762/bjoc.10.53 Abstract A mild and efficient methodology for the bromination

• of phenols and alkenes has been developed utilizing visible light-induced photoredox catalysis. The bromine was generated in situ from the oxidation of Br− by Ru(bpy)33+, both of which resulted from the oxidative quenching process. Keywords: alkenes; bromination; phenols; photoredox catalyst

• ; visible light; Introduction Bromophenols serve as important synthetic intermediates for a variety of naturally occurring biologically active compounds and are also important constituents of industrial chemicals [1][2][3][4][5]. Thus, numerous methods were developed for the electrophilic bromination of

Zirconoarylation of alkynes through p-chloranil-promoted reductive elimination of arylzirconates

• Xiaoyu Yan,
• Chao Chen and
• Chanjuan Xi

Beilstein J. Org. Chem. 2014, 10, 528–534, doi:10.3762/bjoc.10.48

• diphenylacetylene was used as starting material, different aryllithium compounds were employed to afford triarylethylene in 38% to 62% isolated yields after being quenched with HCl (Table 1, entries 1–4). Bromination of the reaction mixture by NBS instead hydrolysis afforded bromotriphenylethylene in 37% isolated

• instead of diphenylacetylene. After bromination by NBS (2 mmol), 3j was isolated in 36% yield. 1H NMR (300 MHz, CDCl3, Me4Si) δ 2.18 (s, 3H), 2.25 (s, 3H), 6.80–7.38 (m, 13H); 13C NMR (75 MHz, CDCl3, Me4Si) δ 21.3, 21.4, 122.1, 127.5, 128.2, 128.7, 128.8, 129.6, 130.3, 130.3, 136.7, 137.8, 138.4, 138.5

Deoxygenative gem-difluoroolefination of carbonyl compounds with (chlorodifluoromethyl)trimethylsilane and triphenylphosphine

• Fei Wang,
• Lingchun Li,
• Chuanfa Ni and
• Jinbo Hu

Beilstein J. Org. Chem. 2014, 10, 344–351, doi:10.3762/bjoc.10.32

• TMSCF3 from fluoroform (CF3H), which paved the way for the synthetic applications of TMSCF3 [38][39]. Moreover, the preparation of TMSCF2Br either by fluoro–bromo exchange reaction of TMSCF3 [34] or by bromination of TMSCF2H [34][40] has also been disclosed. To obtain TMSCF2Cl, we tried the halogen

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• to give pentacycle 172. Reduction of the nitro group was followed by Cbz-protection. Allylic alcohol 173 resulted from radical allylic bromination followed by displacement of bromine through water under silver-catalysis. Eschenmoser–Claisen rearrangement [148] led to the formation of the remaining

Synthesis and determination of the absolute configuration of (−)-(5R,6Z)-dendrolasin-5-acetate from the nudibranch Hypselodoris jacksoni

• I. Wayan Mudianta,
• Victoria L. Challinor,
• Anne E. Winters,
• Karen L. Cheney,
• James J. De Voss and
• Mary J. Garson

Beilstein J. Org. Chem. 2013, 9, 2925–2933, doi:10.3762/bjoc.9.329

• . The overall synthesis (Scheme 1) was adapted from Tsubuki et al. [21]. Furan-3-ylmethanol (4) was prepared in 78% yield by reduction of 2-furoic acid with LiAlH4 in dry diethyl ether, whereas geranyl bromide (5) was obtained through bromination of geraniol with carbon tetrabromide and

Multigramme synthesis and asymmetric dihydroxylation of a 4-fluorobut-2E-enoate

• James A. B. Laurenson,
• John A. Parkinson,
• Jonathan M. Percy,
• Giuseppe Rinaudo and
• Ricard Roig

Beilstein J. Org. Chem. 2013, 9, 2660–2668, doi:10.3762/bjoc.9.301

• purification. Bromination was carried out using the method of Lester et al. [17], and while it was effective at small scales, larger scale (>150 mmol) reactions were violently exothermic. A modification of the reaction order reported earlier by Gershon and coworkers solved the problem [18]. Chlorobenzene was

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

• dihydrofurans 14 and 15 by oxidative azidation (see above) only led to very low yields of the desired α-azidotetrahydrofuranones (6%). The conditions obviously cause decomposition of the auxiliary. As an alternative, the electrophilic bromination of 15 with NBS and the subsequent substitution with sodium azide

• . Subsequent functionalization using oxidative azidation, as shown for methoxy-substituted dihydrofuran 8, did not give the expected α-azidotetrahydrofuranones in acceptable yields, but electrophilic bromination and subsequent substitution with sodium azide turned out to be a good alternative for the synthesis

Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives

• Paola Bonaccorsi,
• Maria Luisa Di Gioia,
• Antonella Leggio,
• Lucio Minuti,
• Teresa Papalia,
• Carlo Siciliano,
• Andrea Temperini and
• Anna Barattucci

Beilstein J. Org. Chem. 2013, 9, 2410–2416, doi:10.3762/bjoc.9.278

• from 9,10-dihydro-9,10-[1',2']benzenoanthracene-2,3,6,7,14,15-hexacarboxylic acid through its hexaethyl ester. However, their yields were very low, 17% in the first step and 26% in the subsequent LiAlH4 reduction/HBr bromination. Moreover 9,10-dihydro-9,10[1',2']-benzenoanthracene-2,3,6,7,14,15

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• Knoevenagel adduct 2.12 and methyl butynoate 2.13 (Scheme 25) [68]. The reaction is reported to progress in high regioselectivity (>50:1) albeit in moderate isolated yield. Following debenzylation of the Diels–Alder product a selective allylic bromination was achieved again in good selectivity (>80:20

• dihydropyridine. This regioselective bromination reaction was studied in some detail by the Warner–Lambert Company and is reported to give superior outcomes when compared to the direct Hantzsch synthesis of non-symmetrical dihydropyridines with respect to product yield (70–90% vs 10–30%) and ease of purification

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