Conformational preferences of α-fluoroketones may influence their reactivity

• Graham Pattison

Beilstein J. Org. Chem. 2017, 13, 2915–2921, doi:10.3762/bjoc.13.284

• ][4] and here their reactivity relative to other halogenated ketones is compared. It is well established that the halogen leaving groups in these substrates are highly activated by orbital overlap with the adjacent carbonyl group, making α-halogenated ketones one of the most reactive classes of

• performed previously to quantify the effects that different α-halogen atoms have on carbonyl reactivity. This paper aims to examine some of the effects that α-halogenation can impart on carbonyl reactivity with a particular emphasis on the effects of α-fluorination. As the most electronegative element

• proceed cleanly, with minimal byproduct formation, and in the case of examining the reactivity of the carbonyl group of α-halogenated ketones, should show very high regioselectivity for nucleophilic addition to the carbonyl group rather than nucleophilic displacement of the halogen atom. Another important

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• in the preparation and application of cyanine dyes as bio-probes [37][38] and our research in this area [39][40][41] has led us to search for novel representatives of this interesting family of compounds. The main goal of the study described here was to investigate the influence of different halogen

• cationic species located in this fragment (electron density, mapped with electrostatic potential for 5a and 5b, Figure 8). Conclusion Two novel cationic compounds 4b and 4c and four asymmetric monomeric monomethine cyanine dyes containing halogen substituents (5a–d) were synthesized by an environmentally

• monofluoro-substituted dye TO-1F. Reagents, conditions and yields: (i) sodium methanethiolate (NaSCH3), 7 h, reflux; (ii) methyl iodide, overnight, overall yield for (i) and (ii) 9%; (iii) 5-fluoro-2,3-dimethylbenzothiazolium iodide and triethylamine, rt, overnight, yield 24%. Synthesis of new halogen

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• ring and the olefinic =CH group (see Supporting Information File 1). The final amination step was achieved following a modified procedure by Marzabadi and co-workers [42]. Catalytic amounts of potassium iodide were added for in situ halogen exchange. The dehydrated products 7a–q were heated in the

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• of an halogen bond between the positive electrostatic potential on the outer side of the chlorine atom and the lone pair of the phosphorus atom of the phosphine. This phenomenon indeed triggered the cleavage of the S–Cl bond, producing chlorophosphonium sulfinate 40, which was then readily converted

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

• -products. The mechanism was similar to previous examples to generate the β-CF3 alkyl radical intermediate 44, which was trapped by halogen atom transfer from the halogenating agent. The nitrogen-centered radical 45 oxidised Mes-Acr* by a single-electron-transfer process to restart the catalytic cycle

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• reacting a heptakis(6-deoxy-6-halo)-β-CD with an excess of a suitable polyamine [37]. The reaction leads to the exhaustive nucleophilic displacement of the halogen atoms on the starting material [38][39]. However, the products obtained constitute complex mixtures of various inseparable derivatives, having

Reagent-controlled regiodivergent intermolecular cyclization of 2-aminobenzothiazoles with β-ketoesters and β-ketoamides

• Irwan Iskandar Roslan,
• Kian-Hong Ng,
• Gaik-Khuan Chuah and
• Stephan Jaenicke

Beilstein J. Org. Chem. 2017, 13, 2739–2750, doi:10.3762/bjoc.13.270

• yields were obtained with 2-aminobenzothiazoles bearing electron donating methyl, dimethyl or methoxy groups (Scheme 2, 3b–d). Halogen substituents F, Cl and Br were well tolerated under the optimized conditions. 2-Aminobenzothiazoles with an ester moiety also proceeded with good yields (Scheme 2, 3h

• substituted 2-aminobenzothiazoles were then screened in this reaction. Electron-donating groups including methyl and methoxy were well tolerated under the reaction conditions (Scheme 3, 5b–d). 2-Aminobenzothiazoles with halogen substituents F, Cl and Br reacted smoothly with excellent yields (Scheme 3, 5e–g

Pyrene–nucleobase conjugates: synthesis, oligonucleotide binding and confocal bioimaging studies

• Artur Jabłoński,
• Yannic Fritz,
• Hans-Achim Wagenknecht,
• Rafał Czerwieniec,
• Tytus Bernaś,
• Damian Trzybiński,
• Krzysztof Woźniak and
• Konrad Kowalski

Beilstein J. Org. Chem. 2017, 13, 2521–2534, doi:10.3762/bjoc.13.249

• observed in the molecular structures of the metallocene–nucleobase derivatives [24][29]. In addition, each molecule of 2 in the dimer is further involved in a Cl···O halogen bond with an adjacent molecule of chloroform (Figure 3). Further details of intermolecular interactions present in the crystal

• –nucleobase conjugates A1–A3. ORTEP diagram of 2 at 50% probability level. The hydrogen and halogen bonds are represented by dashed lines. Selected bond lengths (Å) and angles (°): O26–C17, 1.223(2); O27–C21, 1.233(2); O28–C23, 1.225(2); N20–C25, 1.380(2); N22–C21, 1.372(2); N22–C23, 1.389(2); C1–C17, 1.501(2

• distance = 2.882(2) Å) and halogen bonding (C30–Cl31···O28 distance = 2.972(2) Å) observed in the crystal packing of 2. UV–vis absorption and fluorescence spectra of pyrene–adenines 5 (a) and 3 (b) in diluted (c ≈ 10−5 M) dichloromethane solutions at ambient temperature. Absorption changes during titration

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

• containing a trifluoromethyl group at C-2 and a p-halogen-substituted and non-substituted phenyl-1,2,3-triazole moieties. The synthesis of 2-(trifluoromethyl)-6-phenylquinolone was achieved by Conrad–Limpach reaction of a primary aromatic amine with a β-ketoester [37][38]. Namely, thermal condensation of 4

• 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

• bands at 1099 (Cl), 1077 (Br) and 1064 (I) cm−1 which are assigned to vibration of the phenyl ring that contains the carbon–halogen bond. Characteristic C≡C alkyne band at 2133 cm−1 along with the band at 1258 cm−1 of the triazole products are appropriate for monitoring of the reaction progress. In situ

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• in situ generation of iodotrimethylsilane that result from a halogen exchange reaction [169]. This method (ClSiMe3 + NaI in acetonitrile) is currently less employed likely due to the need to remove NaI from the final phosphonic acid after the step of hydrolysis or methanolysis. It is worth noticing

• carbonyl derivatives 71 [197]. It must be noted that when the organometallic complex possessed halogen–metal moiety, then Me3SiBr can induce halogen exchange [198]. The use of bromotrimethylsilane to prepare phosphonic acid from dialkyl phosphonate is rarely associated with undesired side reactions

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• DBU (1,8-diazabicycloundec-7-ene) under the same conditions as mentioned above, the desired imidazopyridine derivative 7a was isolated in 33% yield (Scheme 4). This one-pot process gives an overall yield very close to the two-step reaction (38%). Further, the halogen-substituted substrate 7e appeared

Mechanochemical Knoevenagel condensation investigated in situ

• Sebastian Haferkamp,
• Franziska Fischer,
• Werner Kraus and
• Franziska Emmerling

Beilstein J. Org. Chem. 2017, 13, 2010–2014, doi:10.3762/bjoc.13.197

• interactions such as hydrogen bonds, halogen bonds, and π∙∙∙π interactions [16][17][18][19]. For example, Toda et al. reported yields of 97% for Aldol condensations in the absence of any solvents [20]. Kaupp et al. described the first Knoevenagel condensation in a ball mill [21]. Compared to conventional

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

• milling, sonication, etc. are certainly of interest to the researchers working on the development of green methodologies. In this review, a collection of examples on recent developments in organic bond formation reactions like carbon–carbon (C–C), carbon–nitrogen (C–N), carbon–oxygen (C–O), carbon–halogen

• alcohols or amines as nucleophile [92]. When 2 equiv of CDI was treated with alcohol in a mixer mill at 30 Hz, within 15 min imidazolecarboxylic acid derivatives were isolated with a new C–O bond formation (Scheme 22). C–X bond forming reactions Carbon–halogen (C–X) bond forming reactions are also

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• (tetraphenylporphyrin) as a photosensitizer has recently been reported to proceed with satisfying selectivities by the groups of Meng and Gao [114][115]. In their first report [114], they made use of the classical cinchona catalyst A5 together with catalytic amounts of TPP under irradiation with a 100 W halogen lamp

Direct catalytic arylation of heteroarenes with meso-bromophenyl-substituted porphyrins

• Alexei N. Kiselev,
• Olga K. Grigorova,
• Alexei D. Averin,
• Sergei A. Syrbu,
• Oskar I. Koifman and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2017, 13, 1524–1532, doi:10.3762/bjoc.13.152

• various pairs of the reagents. More successful arylation of 4-bromophenyl derivatives compared to 3-bromophenyl-substituted porphyrinates is due to a more reactive halogen in these compounds. Generally, benzoxazole and in some cases N-methylbenzimidazole demonstrated the advantage over benzothiazole in

Syntheses of 3,4- and 1,4-dihydroquinazolines from 2-aminobenzylamine

• Jimena E. Díaz,
• Silvia Ranieri,
• Nadia Gruber and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2017, 13, 1470–1477, doi:10.3762/bjoc.13.145

• ]. To our knowledge, selective acylations of N1-alkyl-2-ABAs have not been reported yet. Alkylations of the aliphatic amino group of 2-ABA using triflates, halogen or CCl3 derivatives have also been reported. However, these reactions are frequently associated with long reaction times, poor yields and

Detection of therapeutic radiation in three-dimensions

• John A. Adamovics

Beilstein J. Org. Chem. 2017, 13, 1325–1331, doi:10.3762/bjoc.13.129

• consistent with the bond energy of the carbon–halogen bond. The observed sensitivity was in the order R3C–I > R3C–Br > R3C–Cl [42][43][44]. Due to the high electron density of radical initiators containing iodine even at relatively low concentrations (100 mM) result in dosimeters that are not tissue

Characterization of non-heme iron aliphatic halogenase WelO5* from Hapalosiphon welwitschii IC-52-3: Identification of a minimal protein sequence motif that confers enzymatic chlorination specificity in the biosynthesis of welwitindolelinones

• Qin Zhu and
• Xinyu Liu

Beilstein J. Org. Chem. 2017, 13, 1168–1173, doi:10.3762/bjoc.13.115

• engineering and evolution of these proteins for biocatalyst application. Keywords: alkaloid biogenesis; biosynthetic divergency; C–H activation; halogenase; non-heme iron enzyme; Introduction Carbon–halogen (C–X) bonds are prevalent structural motifs in modern agrochemicals, pharmaceuticals and bioactive

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• switched to the stannane 56 by lithium–halogen exchange and further treatment with Bu3SnCl [92] in 90% yield. The synthesis of the coupling partner 55 started with known Weinreb amide 64 which underwent a syn-selective palladium-catalyzed hydrostannylation and was then transformed to phosphonate 65 in good

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• was developed. The route initiated from compound 4a and pivaloyl-protected glycosyl bromide 2b, the β-C-arylglucoside 5 was obtained with high stereoselectivity in one step after a halogen–lithium exchange/transmetalation/coupling sequence. Cryogenic temperatures and catalysts were not required. The

Synthesis and enzymatic ketonization of the 5-(halo)-2-hydroxymuconates and 5-(halo)-2-hydroxy-2,4-pentadienoates

• Tyler M. M. Stack,
• William H. Johnson Jr. and
• Christian P. Whitman

Beilstein J. Org. Chem. 2017, 13, 1022–1031, doi:10.3762/bjoc.13.101

• , University of Texas, Austin, TX 78712, USA 10.3762/bjoc.13.101 Abstract 5-Halo-2-hydroxymuconates and 5-halo-2-hydroxy-2,4-pentadienoates are stable dienols that are proposed intermediates in bacterial meta-fission pathways for the degradation of halogenated aromatic compounds. The presence of the halogen

• . The implications of these findings are discussed. The availability of these compounds will facilitate future studies of the haloaromatic catabolic pathways. Keywords: dienol; enzyme kinetics; fluoride; halogen; Introduction Aromatic hydrocarbons and their halogenated derivatives are well known

• the actions of pyruvate aldolase and acetaldehyde dehydrogenase would produce 2-chloroacetaldehyde (7b) and 2-chloroacetyl CoA (8b), which are potential alkylating agents of these enzymes as well as other cellular proteins and DNA. This observation and the potential effects of the halogen on other

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• presence of Pd and Cu catalysts to afford (E)-α-selenylstannanes for the synthesis of trisubstituted alkenes [13] and hydrozirconation with further replacement of Zr atom by hydrogen or halogen [14] or their use in the preparation of α-seleno-α,β-unsaturated ketones [15]. Besides, hydrogen halide-addition

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• -diketones with arylhydrazines, halogenation of the resulting 1,3,5-triarylpyrazoles in the 4-position and further functionalization via Negishi cross-coupling [23][24] or halogen–lithium exchange reaction (Scheme 1). The resulting compounds amongst others seem to be interesting as potential complexing

• homocoupling products 7a,b emerged as the predominant reaction products (Scheme 5, middle trace), probably due to preferable halogen–zinc exchange and subsequent homocoupling. Interestingly, such sterically hindered halides provided homocoupling products 7a,b in good yields (66% and 48%, respectively). The

• –halogen exchange and subsequent carboxylation with iodopyrazoles 3a–d. Attempted cross-coupling reactions with 4-halopyrazoles 5 and 3a. Negishi couplings with 4-iodopyrazoles 3a,b. Formation of pyrazoloquinolizin-6-ium iodide 12 upon reaction of 3a with (phenylethynyl)zinc bromide. Prototropic

Metal-free hydroarylation of the side chain carbon–carbon double bond of 5-(2-arylethenyl)-3-aryl-1,2,4-oxadiazoles in triflic acid

• Anna S. Zalivatskaya,
• Dmitry S. Ryabukhin,
• Marina V. Tarasenko,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya,
• Elena V. Grinenko,
• Ludmila V. Osetrova,
• Eugeniy R. Kofanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2017, 13, 883–894, doi:10.3762/bjoc.13.89

• aromatic ring of the styryl group of oxadiazoles 1 play a crucial role for the protonation and reactivity of these compounds. Thus, styryl-substituted oxadiazoles 1b,c and substrates 1f–k, bearing electron-accepting halogen substituents, need higher reaction temperatures up to 60 °C (Table 2, entries 4, 8

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• mercury lamp was replaced with three 100 W halogen bulbs. Dihydroxylation and protection of endoperoxides 18 and 19 to provide novel building blocks 20–23 for azasugar synthesis. Preliminary exploration of the chemistry of endoperoxides 18–23 was encouraging and gave access to a variety of derivatives