Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• membrane core with high bulkiness. BODIPY and BOIMPY scaffolds on the other hand expose fluoride residues which might be able to interact with polarized H–X bonds. Therefore, we synthesized pentaene and hexaene fatty acids which bear five or six double bonds at the terminus or in the middle of the acyl

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• , proteins or antibodies [34][35], mild and fast methods for radiolabeling are mandatory because of the short half-live of [18F]fluoride (t1/2: 110 min). In most cases, indirect radiolabeling is used for these more sensitive biomacromolecules due to the harsh conditions (i.e., organic solvents, high

• temperatures and basic conditions) for the direct incorporation of [18F]fluoride, which can alter the biological/pharmacological behavior or, at least, destroy sensitive biomolecules [36][37][38]. For this purpose, bioorthogonal building blocks were developed using Huisgen-click or the Staudinger ligation

• . Using these methods, a synthesis procedure for both bioorthogonal 18F-building blocks [18F]4b and [18F]5b was developed from their precursors 4a and 5a, respectively (Scheme 4). For this purpose, the nitro group of 4b and 5b was replaced by [18F]fluoride in a nucleophilic aromatic exchange reaction. To

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• peroxyacetal intermediate 12. Then BF3 migrates to another oxygen atom through transition state 13 to give the second Criegee intermediate 14. The decomposition of intermediate 14 finally produces 15, hydrogen fluoride (16) and ester 17. Despite the fact that the Baeyer–Villiger reaction is known since 1899

Palladium-catalyzed picolinamide-directed iodination of remote ortho-C−H bonds of arenes: Synthesis of tetrahydroquinolines

• William A. Nack,
• Xinmou Wang,
• Bo Wang,
• Gang He and
• Gong Chen

Beilstein J. Org. Chem. 2016, 12, 1243–1249, doi:10.3762/bjoc.12.119

• incompatible with directed SEAr, but was iodinated selectively at the ortho position under Pd-catalyzed conditions without the formation of regioisomeric side products. The strong para-directing effect exerted by aryl fluoride substituents overrides directed SEAr selectivity [38][39]. Thus, we observed only

Stereoselective synthesis of tricyclic compounds by intramolecular palladium-catalyzed addition of aryl iodides to carbonyl groups

• Jakub Saadi,
• Christoph Bentz,
• Kai Redies,
• Dieter Lentz,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1236–1242, doi:10.3762/bjoc.12.118

• aryl iodide substituent were prepared following our well-established route via 2-siloxycyclopropane carboxylates D [6][7] that allows a regioselective introduction of the benzylic substituents at the α-carbon [8][9] to give intermediates E (Scheme 2). After fluoride-promoted ring opening [10] the

• serendipitous discovery of the palladium-catalyzed cyclization to products C. Synthesis of compounds A (1–6) via methyl 2-siloxycyclopropanecarboxylates D, their alkylation to E and fluoride-induced ring opening. Palladium-catalyzed reactions of methyl ketone 1 to tetralin derivative 7 and of isopropyl

Synthesis of highly functionalized 2,2'-bipyridines by cyclocondensation of β-ketoenamides – scope and limitations

• Paul Hommes and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2016, 12, 1170–1177, doi:10.3762/bjoc.12.112

• -nonaflation employing nonafluorobutanesulfonyl fluoride provided the expected 4-nonafloxy-substituted bipyridine derivatives 5a–g in moderate to good overall yields. The bipyridyl nonaflates are excellent precursors for palladium-catalyzed reactions as demonstrated by representative Suzuki and Sonogashira

• using nonafluorobutanesulfonyl fluoride (NfF) as sulfonylating reagent. In subsequent publications we could demonstrate that this method can be used to synthesize a variety of functionalized pyridine derivatives, 2,2´-bipyridines or terpyridines [2][3][4]. An alternative entry to the crucial β

• of the cyclocondensation step and subjected the unpurified compounds to the O-nonaflation procedure. Treatment with an excess of sodium hydride in THF followed by reaction with nonafluorobutanesulfonyl fluoride (NfF) afforded the desired 2,2´-bipyridine derivatives 5a–g containing the 4-nonafloxy

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• in 96% yield (98% de) [92][95]. A novel β-selective glycosylation of the 5'-hydroxy group was also established. Thus, 14 was reacted with the ribosyl fluoride 15 and BF3·Et2O, which afforded the glycosylated product 16 in 77% yield and with a β/α-selectivity of 24:1 [91][92]. This reaction was

Gold-catalyzed direct alkynylation of tryptophan in peptides using TIPS-EBX

• Gergely L. Tolnai,
• Jonathan P. Brand and
• Jerome Waser

Beilstein J. Org. Chem. 2016, 12, 745–749, doi:10.3762/bjoc.12.74

• modified reaction conditions (10 mol % AuCl(SMe2), three equivalents TIPS-EBX (1a) and 2 mol % trifluoroacetic acid as co-catalyst) [39]. They also demonstrated that the obtained silylalkyne products can be easily deprotected with fluoride sources to allow bioconjugation via cycloaddition with azides

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

A practical way to synthesize chiral fluoro-containing polyhydro-2H-chromenes from monoterpenoids

• Oksana S. Mikhalchenko,
• Dina V. Korchagina,
• Konstantin P. Volcho and
• Nariman F. Salakhutdinov

Beilstein J. Org. Chem. 2016, 12, 648–653, doi:10.3762/bjoc.12.64

• as fluorine sources. Presumably, the reaction starts with the Prins cyclisation resulting in the formation of cation 10. There are then several mechanistic pathways, some or all of them may be in operation: a) cation 10 may undergo stereoselective trap by [F−] to form fluoride epimers 8; b) cation 10

• may undergo stereoselective trap by H2O to form alcohol epimers 2; these may then undergo a stereospecific SN2 reaction to form fluoride epimers 8; c) the fluorination and/or hydroxylation of cation 10, forming fluoride epimers 8 and alcohol epimers 2, respectively, may be reversible. This has several

• effects: firstly, reversible hydroxylation means that alcohol epimers 2 may convert to fluoride epimers 8 via cation 10 (pathway (a)); secondly, reversible fluorination and/or hydroxylation means that the diastereoselectivity of formation and/or 2 may be governed by product stability and not inherent

Creating molecular macrocycles for anion recognition

• Amar H. Flood

Beilstein J. Org. Chem. 2016, 12, 611–627, doi:10.3762/bjoc.12.60

• presentation of the triazolophanes in 2007 at Yoshito Tobe’s International Symposium on Novel Aromatics (ISNA-12) on Awaji Island, Japan, we undertook a study of the size selectivity [17]. We found triazolophanes are size-matched to chloride and bromide (K ≈ 106 M−1) with fluoride being too small (K ≈ 105 M−1

• biggest surprise (and clearest vindication for the rigidity of the triazolophane macrocycle) is the weak fluoride affinity, being an order of magnitude lower than chloride. Typically, charge-dense fluoride produces the largest affinity when the receptor can conform to the fluoride’s smaller size to

• produce shorter, stronger contacts. Calix[4]pyrroles are a case in point [18]. This conformational rearrangement cannot occur within the triazolophane and so, while the fluoride may have shorter hydrogen bonds, it has fewer contacts than chloride. For iodide, it is simply too big for a single

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• and scyllo-20. Unfortunately, the desired fluorinated products myo-21 and scyllo-21 were not obtained; instead elimination reaction and the formation of unidentified products were observed. Hence, tosylation was next performed, in order to allow the nucleophilic substitution with fluoride at a later

• fully acetylated inositols. The fluorination reactions using potassium fluoride, 18-crown-6 in acetonitrile at 70 °C [53], TBAF in acetonitrile at 60 °C for 2 h [54] or KHF2 and 18-crown-6 in acetonitrile for 2 h at 60 °C [55] were performed. However, 19F NMR analyses of the reaction mixtures did not

• of this hydroxy group is mandatory for labeling with [18F]-fluoride with regard to a PET application. Therefore the acetylation of myo-26 and scyllo-26 using the transacetylization protocol [52] gave the fully acetylated products myo-27 and scyllo-27 in 56% and 52% isolated yields, respectively. The

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• the P(R)-isomers into the CD cavity is followed by the formation of a hydrogen bond between a C-3 hydroxy and the phosphoryl oxygen atom of soman. Then a C-2 ionized hydroxy function attacks the phosphorus atom to form a covalent bond with the release of the leaving group (fluoride ion). The different

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• -tetramethylpiperidine-N-oxyl (TEMPO) [36]. NFSI is a very interesting reagent. Besides classic electrophilic fluorination reagent [37], it has been used not only as fluoride-atom transfer reagent [38][39][40] but also as nucleophilic/radical amination reagent [41]. We are highly interested in the multiple reaction

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• . This report suggests that TFA can act as a trifluoromethyl source in the reaction with inactivated aromatic compounds, while the control of regioselectivity is difficult. Trifluoromethylation with difluorocarbene and fluoride ions The reaction system with ClCF2CO2Me/KF/CuI also generates CF3Cu in situ

• [40][41] (Scheme 7). The demethylation of ClCF2CO2Me proceeds by iodide, followed by decarboxylation of the resulting chlorodifluoroacetate to provide difluorocarbene (:CF2), trapped by fluoride to give the CF3− species. This reacts with CuI leading to CF3Cu. The method described above for the

• trifluoromethylation of aryl iodides with ClCF2CO2Me and fluoride can be utilized for clinical studies. Herein, we introduce one example of decarboxylative [18F]trifluoromethylation for positron emission tomography (PET) studies. A synthetic methodology for [18F]labelled-CF3 arenes is desired for the application of

Computational study of productive and non-productive cycles in fluoroalkene metathesis

• Markéta Rybáčková,
• Jan Hošek,
• Ondřej Šimůnek,
• Viola Kolaříková and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2015, 11, 2150–2157, doi:10.3762/bjoc.11.232

• cycle shows that the transition state energies differ by more than 120 kJ/mol, making thus the first part A of the productive cycle highly improbable and probably resulting in stopping the productive metathesis of vinylidene fluoride at all, because all active catalytic species AC move forth and back in

Stereoselective synthesis of hernandulcin, peroxylippidulcine A, lippidulcines A, B and C and taste evaluation

• Marco G. Rigamonti and
• Francesco G. Gatti

Beilstein J. Org. Chem. 2015, 11, 2117–2124, doi:10.3762/bjoc.11.228

• cleavage of the silyl protective group of 11 with tetra-n-butylammonium fluoride (TBAF) in MeCN and at room temperature, the spectroscopic data of 1 were in complete agreement with those reported in literature [6] ([α]D +130° (c 1.6, CHCl3) vs lit. [31] ([α]D +115° (c 0.64, CHCl3)). The photooxygenation

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• . When 70% HF·Py was employed, up to 70% conversion was achieved, but with over-fluorination to generate only the difluoromethylene thioether 4a (not isolated). In view of the lack of control with HF·Py attention turned to triethylamine trihydrogen fluoride (3HF·Et3N). This proved unsuccessful presumably

• 3HF·Et3N. In light of these observations, our working hypothesis is that the Lewis acid acts to increase the acidity of the 3HF·Et3N by sequestering fluoride ions as relatively unreactive metal fluorides; thus, the alkynyl sulfides are activated by protonation possibly through an intermediate such as A as

• illustrated in Scheme 3. Such an intermediate would then be susceptible to fluoride ion attack, and progress to the reaction products. The major cis stereoselectivity is consistent with the attack of an intermediate such as A from the less hindered face, opposite to the R1 substituent (Scheme 3). Conclusion

Nitro-Grela-type complexes containing iodides – robust and selective catalysts for olefin metathesis under challenging conditions

• Andrzej Tracz,
• Mateusz Matczak,
• Katarzyna Urbaniak and
• Krzysztof Skowerski

Beilstein J. Org. Chem. 2015, 11, 1823–1832, doi:10.3762/bjoc.11.198

• the first Z-selective catalysts [18][19][20][21]. Their efficiency, however, is noticeably lower than that observed for classical complexes. The second generation indenylidene catalysts with phosphite ligand (frequently reported as “Cazin-type catalysts”) bearing mixed chloride–fluoride or difluoride

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• indole catalyzed by potassium fluoride in alumina and a sufficient amount of 18-crown-6. The product obtained from this reaction was decarboxylated by copper chromite and quinolone to yield arnoamine B. This latter was then demethylated with boron tribromide to afford arnoamine A (40, Scheme 5) [63

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• development of a method for the one-pot deprotection/CuAAC began with Cu(I) chloride and a survey of solvents reported [2] for triazole formation (Table 1). TIPS-protected propargylamine 4a and benzyl azide (5a) are heated in the presence of 1.5 equivalents of TBAF (tetrabutylammonium fluoride), 5 mol % CuCl

Tetrathiafulvalene-based azine ligands for anion and metal cation coordination

• Awatef Ayadi,
• Aziz El Alamy,
• Olivier Alévêque,
• Magali Allain,
• Nabil Zouari,
• Mohammed Bouachrine and
• Abdelkrim El-Ghayoury

Beilstein J. Org. Chem. 2015, 11, 1379–1391, doi:10.3762/bjoc.11.149

• N3–H3···O1 hydrogen bonding. Titration experiments with inorganic anions showed that both ligands are suitable candidates for the sensing of fluoride anions. Ligand L2 was reacted with a Re(I) cation to yield the corresponding rhenium tricarbonyl complex 3. In the crystal structure of the newly

• prepared electroactive rhenium complex the TTF is neutral and the rhenium cation is hexacoordinated. The electrochemical behavior of the three compounds indicates that they are promising for the construction of crystalline radical cation salts. Keywords: azine ligand; fluoride sensing; rhenium

• properties of both anions and metal cations [23][24][25][26][27]. In fact, anions are involved in a large number of biological and chemical processes [28][29][30][31]. Note that fluoride is of particular interest among the other inorganic anions because of its both beneficial (e.g., preventing dental caries

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• cyclopropane derivatives 30 (62%) and 32 (44%). Later, Michael addition in the presence of caesium fluoride and benzyltriethylammonium chloride in DMF gave the benzannulated cyclodecanone derivatives 31 (11%) and 33 (10%) (Scheme 2). Oxymercuration – Hantzsch pyridine synthesis: Kondo and Miyake [86] have

• -diiodobenzene with an excess amount of triisopropylsilylbutadiyne (47) followed by complexation with Co2(CO)8 furnished a pale yellow diyne 48. Exchange of the ligand with bis(diphenylphosphino)methane (dppm) afforded a bridged complex which is stable to fluoride ions. Subsequent desilylation, followed by

Advances in the synthesis of functionalised pyrrolotetrathiafulvalenes

• Luke J. O’Driscoll,
• Sissel S. Andersen,
• Marta V. Solano,
• Dan Bendixen,
• Morten Jensen,
• Troels Duedal,
• Jess Lycoops,
• Cornelia van der Pol,
• Rebecca E. Sørensen,
• Karina R. Larsen,
• Kenneth Myntman,
• Christian Henriksen,
• Stinne W. Hansen and
• Jan O. Jeppesen

Beilstein J. Org. Chem. 2015, 11, 1112–1122, doi:10.3762/bjoc.11.125

• amidation of aryl halides [51][52]. Examples of TTF derivatives synthesised using this protocol by other groups include: MPTTF and BPTTF-triarylamine conjugates (as possible charge-transport materials) [53], MPTTF-triarylborane conjugates (with possible applications as fluoride sensors) [54], and MPTTF

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• clusters 13 in high yields. As judged by 11B NMR, no fluoride displacement occurred at the boron center during the deprotection step. The synthesis of the 4-valent pyrene-based iminosugars 15 was performed in a similar manner than for BODIPY-based clusters 13 (Scheme 3). The tetrayne 5 synthesized in 3