Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• groups to control a wide variety of biological process photoreversibly [8][9]. Furthermore, chemists have paid attention to spectral tuning of the AB chromophore [10][11]. Recently, an improved set of fluorine-substituted AB photochromes was developed by Hecht and co-workers [12][13]. ABs with two or

A combinatorial approach to improving the performance of azoarene photoswitches

• Joaquin Calbo,
• Aditya R. Thawani,
• Rosina S. L. Gibson,
• Andrew J. P. White and
• Matthew J. Fuchter

Beilstein J. Org. Chem. 2019, 15, 2753–2764, doi:10.3762/bjoc.15.266

• scaffold, the theoretical calculations at the PBE0-D3/6-31G** level indicate that an insertion of electron-poor fluorine atoms in the ortho-position of the aryl ring (4pzH-F1 and 4pzH-F2) leads to an increase in the half-life from ca. 1000 days in 4pzH to 2000 days in 4pzH-F1 and to 4000 days in 4pzH-F2

• noncovalent forces are also predicted in the twisted Z-isomers of the 4pzMe-X family, for which θ remains approximately constant. Furthermore, the atomic charge of fluorine is calculated to be ca. −0.30e, which allows for electrostatic interactions with positively charged C atoms (ca. +0.40e) of the pyrazole

• . Thus, a tilting of the pyrazole moiety away from orthogonality with respect to the plane generated by the aryl ring leads the n–π* excitation to be symmetry-allowed, with the corresponding increase in intensity. For example, the heteroring in fluorine-substituted 4pzH-F2 photoswitch is tilted with a θ

Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• on 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (1) as the starting compound. The presence of fluorine atoms on the four phenyl rings at the meso-positions of the porphyrin structure can make a strong influence on the hydrophobic interactions and lipophilicity, metabolic stability, thus modulating

• . Complexes 2a and 2b readily reacted with the excess of NaN3 in DMF/DMSO to afford porphyrins 3a and 3b in high yields via the selective substitution of fluorine atoms in the para-position of the pentafluorophenyl substituents with four azide functions. The subsequent reduction of para-tetraazidoporphyrinato

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• an improved TM difference between the trans- and cis-PNA15(oF4Azo)2 10 (up to ≈3.7 °C), which was the best for our system. Azobenzene (Azo)-containing PNAs behaved similarly to PNA(oF4Azo) (Table 2), which verified that the fluorine substitution did not affected the binding properties. The

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• visible that could be readily interpreted as the reaction intermediate F-Dola, as well as a single diphosphate moiety. The FGGDP molecule – functionalized with a fluorine atom at the C2 position of its isoprenoid unit – can interfere with the propagation of the generated carbocation(s). Such cyclization

• the active site of CotB2wt·Mg2+3·F-Dola [37] superimposed with CotB2wt·Mg2+B·GGSDP [36]. (A) The bound F-Dola reaction intermediate is shown in magenta with the fluorine atom colored in light blue, and Mg2+ions are shown in green. Residues of the DDXD motif are shown in red and residues of the NSE

• in panel A, the pyrophosphate sensor motif is depicted in pink. View into the active site of CotB2wt·Mg2+3·F-Dola [37]. Identical view as in Figure 4. (A) The bound F-Dola reaction intermediate is shown in magenta with the fluorine atom colored in light blue, and Mg2+-ions are shown in green

Mono- and bithiophene-substituted diarylethene photoswitches with emissive open or closed forms

• A. Lennart Schleper,
• Mariano L. Bossi,
• Vladimir N. Belov and
• Stefan W. Hell

Beilstein J. Org. Chem. 2019, 15, 2344–2354, doi:10.3762/bjoc.15.227

• , substitution of fluorine and/or the addition of nucleophiles to the electron-poor double bond take place. Therefore, tert-butyl protection is required for carboxylates present in diarylethenes with “oxidized” benzothiophene units and perfluorocyclopentene rings. Photoswitches containing the free carboxylic

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• of the ester group in 2’-position, an isopropyl ester derivative; another one might be the effects of the fluorine atoms and the ester group on the HOMO energy level of the benzene moiety. Since our group is interested in PET-active near-infrared (NIR) dyes for bimodal medical imaging (PET/optical

• (pyridine numbering) group. Since the smaller 2’-fluorine substituent in 16 should lead to a decrease in quantum yield compared to 15, we aimed for a molecule with an additional bulky 4’-substituent such as bromine. The bromine should not only alter the HOMO energy level of 16 in a favourable way, it can

• rearrangement. By our optimized procedure, we have obtained the dye 15 at high yield and without the necessity of HPLC purification. The chlorine atom in 2’-position can potentially be used to introduce the PET radionuclide fluorine-18 while the bromine atom serves as a constraint against rotation around the

Perspective isomorphs – a new classification of molecular structures based on artistic and chemical concepts

• Jannis Neumann,
• Ansgar Schnurr and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2019, 15, 2319–2326, doi:10.3762/bjoc.15.224

• the artistic presentation is determined as 2250 mm from the eye to the center of the first atom of the perspective isomorph. On this scale the perspective shortening can be neglected. In the examples described in this report only the elements hydrogen, carbon, nitrogen, oxygen, and fluorine have been

• taken into consideration to illustrate the general concept. To illustrate the concept methane, fluoromethane, and difluoromethane are compared (Figure 1). If fluoromethane is orientated in a way that the observer’s point of view is along the carbon–fluorine bond, it appears indistinguishable from

• methane in the analogous orientation since the fluorine atom is hidden behind the carbon atom. Difluoromethane, however, cannot be viewed in a similar orientation; the second fluorine atom is always visible. Hence, only methane and fluoromethane are perspective isomorphs while difluoromethane is not

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• , Qingdao 266000, China University of Chinese Academy of Sciences, Beijing 100049, China State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Qingdao 266237, China 10.3762/bjoc.15.218 Abstract Fluorine chemistry plays an increasingly important role in pharmaceutical

• , agricultural, and materials industries. The incorporation of fluorine-containing groups into organic molecules can improve their chemical and physical properties, which attracts continuous interest in organic synthesis. Among various reported methods, transition-metal-catalyzed fluorination/fluoroalkylation

• has emerged as a powerful method for the construction of these compounds. This review attempts to describe the major advances in the transition-metal-catalyzed incorporation of fluorine, trifluoromethyl, difluoromethyl, trifluoromethylthio, and trifluoromethoxy groups reported between 2011 and 2019

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• azobenzenes with different halogen bonding donor properties are discussed in relation to their changing photophysical properties, rationalized by DFT calculations. Keywords: azobenzene; DFT calculations; fluorine chemistry; halogen bonding; photochemistry; Introduction The halogen bond is an attractive

• substituting azobenzenes in the ortho-positions to the N=N bond with electron-withdrawing fluorine substituents [45][46], the red-shifting of the n→π* transitions enables selective addressing of both the E- and Z-isomer using visible light. Stabilization of the n-orbitals in the Z-isomers leads to a very high

• Information File 1, Figures S1 and S12). By introduction of fluorine atoms ortho to the azo bond, the two n→π* of E- and Z-state become sufficiently separated to address them individually using visible light sources. Along with averting UV light for the photochemical reaction, high PSS ratios can be observed

A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes

• Joza Schmitt and
• Scott T. Handy

Beilstein J. Org. Chem. 2019, 15, 1781–1785, doi:10.3762/bjoc.15.171

• shift of this lambda max by roughly 40 nm to around 338 nm, presumably due to their donating effect and conjugation with the carbonyl oxygen. Halogen substituents at the 6-position generally had little effect, with the exception of the most electron-withdrawing fluorine, which resulted in a slight blue

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• Supporting Information File 1), whose spectra feature characteristic constant couplings of 16.2 and 16.1 Hz. It is worth mentioning that the fluorine substitution was performed on the boron center after introduction of the styryl residues, introduction prior to the Knoevenagel reaction is known to impede it

• observed in BOD-TTPA-alk is likely due to the boron center alkylation. Similar effects have been already shown after fluorine substitution of BODIPY [33]. 5. DSSCs fabrication and device performances In order to investigate the photovoltaic performances of the two functional dyes BOD-TTPA-alk and BOD-TTPA

Synthesis of 9-O-arylated berberines via copper-catalyzed C_Ar–O coupling reactions

• Qiaoqiao Teng,
• Xinhui Zhu,
• Qianqian Guo,
• Weihua Jiang,
• Jiang Liu and
• Qi Meng

Beilstein J. Org. Chem. 2019, 15, 1575–1580, doi:10.3762/bjoc.15.161

• respective BBR derivatives in high yields. More important, the method allows the incorporation of pharmaceutically highly interesting fluorine-substituted aryl groups into the BBR skeleton. Interestingly, only a single cross-coupling product was observed with 1,4-diiodobenzene, affording tetrahydroberberine

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• ; sulfoxidation; Introduction Fluorine and fluorinated substituents are routinely used to modify the properties of lead compounds in medicinal chemistry and in bioactive discovery programmes [1][2]. To this end, aryl–F and aryl–CF3 are the most common modifications found in compounds registered in the patent

• metabolites which did not contain fluorine. This points to a hydrolytically stable motif over the period of the incubation. In an effort to establish the sequence of events through which these metabolites are generated, each was separately re-incubated with C. elegans to establish if they could be further

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• -arylsulfonyl fluoride 3 was 95% intact in rat plasma after 120 min at 37 °C [5]. This indicated that the combination of electron-donating effects and steric hindrance of isopropyl groups provide greater stability to a sulfur–fluorine bond than groups that can only provide the steric hindrance in the molecule

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks

• Sebastian Hamer,
• Fynn Röhricht,
• Marius Jakoby,
• Ian A. Howard,
• Xianghui Zhang,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1331–1338, doi:10.3762/bjoc.15.132

• eventually also interfere with the coordination chemistry of MOF formation. We therefore considered benzoannelation with 1,3-dioxole (4) and 1,4-dioxane (5) units as electron-donating substituents instead of amino units and substitution with fluorine (1 and 2) to replace the cyano units. Almost free rotation

Mechanochemical amorphization of chitin: impact of apparatus material on performance and contamination

• Thomas Di Nardo and
• Audrey Moores

Beilstein J. Org. Chem. 2019, 15, 1217–1225, doi:10.3762/bjoc.15.119

• . Contamination by fluorine containing species is harder to establish by ICP–OES, so in order to measure potential release when milling in PTFE, we turned to XPS (Figure S1, Supporting Information File 1). When milling in a PTFE jar with ZrO2, fluorine was found in the high concentration of 6.9%. This very high

Synthesis of aryl cyclopropyl sulfides through copper-promoted S-cyclopropylation of thiophenols using cyclopropylboronic acid

• Emeline Benoit,
• Ahmed Fnaiche and
• Alexandre Gagnon

Beilstein J. Org. Chem. 2019, 15, 1162–1171, doi:10.3762/bjoc.15.113

• was produced in a low 31% yield. Electron-withdrawing groups such as a fluorine, bromine, chlorine, trifluoromethyl and a nitro group as well as electron-donating groups such as a methoxy group at the para-position were found to be well tolerated, as indicated by aryl cyclopropyl sulfides 1h–m which

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• substituents other than fluorine could be prepared, as they were dehalogenated during the final debenzylation. Galectin binding Galectin-1, -3, -4C (C-terminal CRD), -4N (N-terminal CRD), -7, -8C, -8N, -9C, and -9N affinities for (aryltriazolyl)methyl galactopyranosyls 1a–n were determined in a competitive

• between the 4-methylphenyl 1h and the 4-trifluoromethylphenyl 1k is interesting, suggesting that the affinity of 1k may be explained by fluorine interaction(s) and/or solvation effects. Of particular interest is the different difluorinated aryls 1e–g, which show a reversed selectivity pattern. They

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• indicated that trifluoromethylation is an excellent tool for the detection of surface-bound materials by XPS. Keywords: chromophore; diaminoterephthalate; fluorine surface marker; fluorescence dye; lipoic acid; self-assembled monolayers; Introduction Diaminoterephthalates (DATs) are powerful fluorescence

• similar chemical shifts in binding energies, fragments of larger organic compounds are not easily distinguished. Labeling molecular entities with elements possessing large excitation cross sections like fluorine, chlorine, or bromine [40] represents an approach that can greatly simplify the detection of

• α-lipoic acid (ALA) residue. Furthermore, a fluorine-substituted moiety bound to DAT shall facilitate detection by XPS. Results and Discussion Synthesis. The preparation of DAT–ALA conjugate 3 with a fluorinated residue started from mono-carbamate-protected diethyl DAT 1 (Scheme 1). Compound 1 was

Halogen bonding and host–guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

• Fangfang Pan,
• Mohadeseh Dashti,
• Michael R. Reynolds,
• Kari Rissanen,
• John F. Trant and
• Ngong Kodiah Beyeh

Beilstein J. Org. Chem. 2019, 15, 947–954, doi:10.3762/bjoc.15.91

• acetonitrile. The 1H and 19F NMR spectra of all these samples were recorded at 298 K and analyzed. In the 19F NMR analyses, the fluorine signals of the XB donor DIOFB were monitored. In all cases, minor upfield shifts of the fluorines on the terminal carbons were observed (0.12 ppm in 1·DIOFB, 0.13 ppm in 1

• ·DIOFB·MeOH and 1·DIOFB·MeCN, Figure 5). Minimal changes (<0.03 ppm) were observed for the fluorine atoms attached to the internal carbon atoms. This strongly suggests that a similar XB involving the iodine atoms of DIOFB exists in solution both with and without the guests (Figure 5). To complement the direct

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• carbocationic center and the closest fluorine atom was 3.084 Å in the methylium-PF6 salt 10{4,4,8}, and 3.275 Å in case of the 10{4,4,11} salt. Moreover, C–H···F interactions where also observed, with H···F bond distances between 2.094 Å and 2.575 Å. Conclusion A facile one-pot method for the three-component

Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

• Laize A. F. Andrade,
• Lucas A. Zeoly,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

• electrostatic repulsion. The conformational behavior changes in the more polar pyridine solution, where the double fluorine gauche effect takes place, since F-2 is preferably gauche to both diastereotopic fluorines. An analysis of the rotation around the N–C(F2) bond indicates the manifestation of anomeric

• manifests in six-membered rings when 1JC–Hax < 1JC–Heq [8][9]. A similar effect on 1JC–F has been observed on fluorinated six-membered rings and then called the (reverse) fluorine Perlin-like effect [10]. Despite some controversies on the origin of such effects [11][12][13][14], the anomeric-like

• incoming fluoride becomes magnetically more shielded than the fluorine not involved in such an interaction. Because the positioning of neighboring groups relative to the diastereotopic fluorines (NEt2 and CHFCF3 groups), the conformational preferences of Ishikawa´s reagent molecule may be influenced by the

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• -position of the aromatic group at C3 significantly affected the diasteomeric ratio with an increase observed with the mesomeric donor methoxy group in favor of diastereomer 7b (7b/7’b = 78:22) compared to 7a/7’a, and a drop of diastereoselectivity when a fluorine atom (7c/7’c = 60:40) or a hydrogen atom

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• -iodonaphthalene gave a relative low yield of 64% (y-2). Gratifyingly, the reaction of disubstituted iodine substrates proceeded smoothly to deliver targeted compounds y-7, y-8, y-14 and y-15 as well. Introducing electron-withdrawing groups at the ortho-position of aryl iodides, such as nitro, fluorine, chlorine