Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

•  29). 2.4. Fluorodehydroxylation of β-hydroxyphenylalanine Alternatively, Kollonitach et al. prepared racemic 3-fluorophenylalanine (136) through the fluorodehydroxylation of 3-hydroxyphenylalanine (137) using sulfur tetrafluoride (SF4) in HF [67] (Scheme 30). 2.5. Ring opening of aziridine

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• amides (Scheme 43) [93]. Singlet oxygen in heteroatom oxidations Singlet oxygen reacts readily with electron pairs of heteroatoms, such as sulfur, selenium, phosphorus, and nitrogen, due to their electrophilicity. The interaction between singlet oxygen and the heteroatom occurs in both physical and

• chemical quenching leading to the formation of covalent products [67]. Sulfur oxidation: One of the first examples reported for heteroatom oxidation by singlet oxygen was the oxidation of sulfides to sulfoxides [67]. Sulfoxides are important intermediates in organic synthesis, and with applications in

• medicine and pharmacology [94], justifying many studies on this topic. The accepted mechanism for sulfide oxidation to sulfoxide involves the chemical quenching of singlet oxygen by sulfur compounds which leads to the persulfoxide intermediate. From this intermediate, a variety of reaction pathways are

Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles

• Ming-Xi Bi,
• Shuai Liu,
• Yangen Huang,
• Xiu-Hua Xu and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62

• and agrochemical industries [3][4][5]. Traditional methods to access these compounds mainly include halogen–fluorine exchange of halomethyl sulfides and trifluoromethylation of sulfur-containing compounds [6][7][8]. Over the last decade, tremendous efforts have been triggered to develop methods for

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• -, oxygen-, and sulfur-containing ligands were investigated soon after the disclosure of the auxiliary effect of ligands on copper-catalyzed alkyne–azide cycloaddition reactions [16][17]. Heterogeneous catalysts are safer than their homogeneous counterparts. They also offer some advantages, such as the ease

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• ][24][25][26][27][28][29]. Among these is an elegant, highly effective approach that led to β-hydroxy, β-mercapto, and β-amino-substituted diorganyl diselenides and selenides. This was accomplished by the opening of three-membered oxygen-, sulfur- and nitrogen-containing heterocycles under the action

• which is more than one order of magnitude greater than the effect of the sulfur atom. This was established based on the determination of the absolute and relative rates of nucleophilic substitution of chlorine in 2,6-dichloro-9-selenabicyclo[3.3.1]nonane and 2,6-dichloro-9-thiabicyclo[3.3.1]nonane [36

• are important features of this approach. The obtained compounds represent novel ensembles of functionalized unsaturated five-membered heterocycles containing one sulfur atom and two selenium atoms of different nature (Schemes 8–11), which are valuable scaffolds for organic synthesis and medicinal

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• produce 3g and 3h, respectively. An arylalkyne 1 possessing an electron-withdrawing group (ester) yielded 3i without affecting the reactivity of 2. Sulfur functional groups tend to decrease the catalytic activity of copper salts, but thienyl-substituted alkyne 1 reacted with 2a to produce 3j in 48% yield

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• takes place for the generation of the S-centered radical 57. The reactive aryl radical 58 is obtained by the cyclization of the sulfur-based radical 57. Simultaneously, photocatalyst 11 is regenerated from Ru(I) photocatalyst 51 and Co(III) complex 56. Additionally, the Co(I) complex 54 and the cation

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• these latter do not adopt the same conformation, according to whether they carry a sulfur atom or not. Obviously, the inductive effects alone are inconsistent with the observed results. Hence, we considered the rigid-core (RC) and the terminal chains separately in order to identify a possible

• , (b”) side view; 2b, conformation C, (c) front view, (c’) top view, (c”) side view. Carbon atoms are shown in gray, hydrogen atoms in white, sulfur atoms in yellow, nitrogen atoms in blue, oxygen atoms in red and fluorine atoms in orange. Vector of dipole moment of compounds 4c, 4b and 2b. Plot of

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• reported that introducing electron-donating groups (methoxy, dimethylamino) in para-position to the thioindoxyl sulfur atom restored E-stability while maintaining red-shifted absorption maxima. This para-position was occupied by the key methoxy group in all our HITub designs. With scant information

• the sulfur atom, for maximal simplicity, we tested whether both substituents could be deleted simultaneously (HITub-4). This proved to be the strongest-performing compound of our studies, with the Z-isomer possessing an EC50 value of ca. 110 nM and a 4-fold difference of bioactivity between lit and

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• Marie Curie-Skłodowska Sq., 20-031 Lublin, Poland 10.3762/bjoc.16.11 Abstract β-Hydroxyalkylphosphine sulfides undergo [1,3]- or [1,4]-sulfur atom phosphorus-to-carbon migration in the presence of Lewis or Brønsted acids. The direction of sulfur atom migration depends on the type of acid used for the

• reaction. In the presence of a Brønsted acid, mainly [1,3]-rearrangement is observed, whereas a Lewis acid catalyzes the [1,4]-sulfur migration. To gain insight into the mechanism of these transformations, the stereochemistry of these rearrangements have been tested, along with the conduction of some

• control experiments and DFT calculations. Keywords: Brønsted and Lewis acids; DFT; mechanistic studies; rearrangement; stereochemistry; sulfur atom migration; Introduction Among all organic reactions, rearrangements are an exciting class of transformations where unusual or even unexpected products can

Microwave-assisted synthesis of 2-substituted 4,5,6,7-tetrahydro-1,3-thiazepines from 4-aminobutanol

• María C. Mollo,
• Natalia B. Kilimciler,
• Juan A. Bisceglia and
• Liliana R. Orelli

Beilstein J. Org. Chem. 2020, 16, 32–38, doi:10.3762/bjoc.16.5

• analogous effect was sometimes observed even in the sulfur analogues, as previously mentioned [32]. The differences between oxygen and sulfur regarding electronegativity and polarizability may explain the differential behaviour of the PPSE promoted ring closure of tetramethylenic amido and thioamido

• energy associated to the formation of a seven-membered heterocycle would favour the competitive ring closure leading to the five-membered ring (Scheme 2, reaction a), which would involve attack of the carboxamide nitrogen to the ω-carbon. On the other hand, the higher nucleophilicity of the sulfur in the

Palladium-catalyzed synthesis and nucleotide pyrophosphatase inhibition of benzo[4,5]furo[3,2-b]indoles

• Hoang Huy Do,
• Saif Ullah,
• Alexander Villinger,
• Joanna Lecka,
• Jean Sévigny,
• Peter Ehlers,
• Jamshed Iqbal and
• Peter Langer

Beilstein J. Org. Chem. 2019, 15, 2830–2839, doi:10.3762/bjoc.15.276

• , Asn245, Glu275, Tyr289, Leu239, Ser326, Thr205, His329 and Glu322 were involved in the hydrogen binding with suramin. One π–alkyl interaction was found with Pro288 and one metal interaction with zinc. Amino acid Tyr289 was connected with the sulfur atom as shown in Figure 5a. The hydrogen atoms of the

Synthesis of aryl-substituted thieno[3,2-b]thiophene derivatives and their use for N,S-heterotetracene construction

• Nadezhda S. Demina,
• Nikita A. Kazin,
• Nikolay A. Rasputin,
• Roman A. Irgashev and
• Gennady L. Rusinov

Beilstein J. Org. Chem. 2019, 15, 2678–2683, doi:10.3762/bjoc.15.261

• transfer because of their tendency to π-stack, with non-bonded sulfur–sulfur interactions in the solid state, which results in large intermolecular orbital coupling of HOMOs and, as a consequence, enhanced carrier transport properties [10]. However, there is a problem of poor solubility of a number of S

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• through time-of-flight matrix assisted laser desorption ionization (MALDI–TOF–MS) mass spectrometry, using sulfur as a matrix. Suzuki–Miyaura coupling to form m,p’-quaterphenyl (13) [35]: 4-Biphenylboronic acid (0.18 g, 0.91 mmol) and 1 M K2CO3 (1.5 mL) were added to a 10 mL Pyrex microwave tube. 3

A toolbox of molecular photoswitches to modulate the CXCR3 chemokine receptor with light

• Xavier Gómez-Santacana,
• Sabrina M. de Munnik,
• Tamara A. M. Mocking,
• Niels J. Hauwert,
• Shanliang Sun,
• Prashanna Vijayachandran,
• Iwan J. P. de Esch,
• Henry F. Vischer,
• Maikel Wijtmans and
• Rob Leurs

Beilstein J. Org. Chem. 2019, 15, 2509–2523, doi:10.3762/bjoc.15.244

• ). When the group Y is OMe (6f), this shift is larger due to the higher EDG properties of MeO (λmax = 352 nm) and this is slightly increased with Y = OiPr (6g, λmax = 355 nm). The shift is highest for Y = NMe2 (6i, λmax = 387 nm). When the oxygen atom of 6f is replaced by a sulfur atom, the bathochromic

• shift of the π–π* band is also increased (6h, λmax = 373 nm, Table 3, Figure 4A). This high capacity of sulfur substituents to induce a bathochromic effect has already been reported in the azobenzene field [33]. The trans–cis photoisomerization for 3e, 4d, 6b and 6d–h in general gives a high percentage

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• . These silver(I) complexes adopted similar structures in solution and in the solid state. As each sulfur atom in the ligand is prochiral, macrocycles L2M2 were obtained as mixtures of diastereoisomers, depending on the configurations of the sulfur atoms coordinated to silver cations. The X-ray structures

• silver(I) catalysts based on sulfur ligands were reported so far, although alkyl thioethers are soft σ-donor ligands such as crown thioethers that were largely developed as macrocyclic ligands for silver(I) [35][36][37][38][39][40][41][42][43]. Interestingly, depending on their design, these known silver

• prochiral sulfur atom of the ligand becomes asymmetric by coordination to silver(I). In absence of any chiral source, the complexes were obtained either as nonchiral coordination products with a center or an axis of symmetry (1a and 1c, with (R,S)–1 ligands) or as a racemic mixture (1d, with (R,R)–1 or (S,S

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

• the structure of CotB2wt·Mg2+B·GGSDP are shown in gray. The GGSDP molecule is shown in black with the sulfur atom colored in yellow. The position of Mg2+B is identical in both structures. For clarity water molecules have been omitted. (B) View in panel A rotated by 30°. In addition to the motifs shown

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• Supporting Information File 1) were observed at remarkable high Tpeak values (193.9–210.1 °C). Following these results, it has been intriguing to analyze the influence of the heteroatom in the heterocyclic moiety on the thermal decomposition process. The change of one nitrogen atom to sulfur as in thiazole

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

Synthesis and properties of sulfur-functionalized triarylmethylium, acridinium and triangulenium dyes

• Marco Santella,
• Eduardo Della Pia,
• Jakob Kryger Sørensen and
• Bo W. Laursen

Beilstein J. Org. Chem. 2019, 15, 2133–2141, doi:10.3762/bjoc.15.210

• functionalities were synthesized and their optical properties were studied. The sulfur functionalities were introduced by aromatic nucleophilic substitution of methoxy groups in triarylmethylium cations with ethanethiol followed by partial or full ring closure of the ortho positions with nitrogen or oxygen

• bridges leading to sulfur-functionalized acridinium, xanthenium or triangulenium dyes. For all the dye classes the sulfur functionalities are found to lead to intensely absorbing dyes in the visible range (470 to 515 nm), quite similar to known analogous dye systems with dialkylamino donor groups in place

• of the ethylthiol substituents. For the triangulenium derivatives significant fluorescence was observed (Φf = 0.1 to Φf = 0.3). Keywords: acridinium dyes; aromatic nucleophilic substitution; fluorescent dyes; sulfur-functionalized dyes; triangulenium dyes; triarylmethylium; Introduction The design

Friedel–Crafts approach to the one-pot synthesis of methoxy-substituted thioxanthylium salts

• Kenta Tanaka,
• Yuta Tanaka,
• Mami Kishimoto,
• Yujiro Hoshino and
• Kiyoshi Honda

Beilstein J. Org. Chem. 2019, 15, 2105–2112, doi:10.3762/bjoc.15.208

• hexafluorophosphoric acid (Scheme 1a and 1b) [3][4][9][10], oxidation of thioxanthene in the presence of PbO2 followed by dehydration by tetrafluoroboric acid [1], the reaction of 4,4’-bis(dimethylamino)diphenylmethane with sulfur in the presence of ZnCl2 [11], and the ring-closure reaction of diaryl sulfide in the

• sulfur were performed with a CHNOS Elemental Analyzer Vario ELIII Elemental (Elementar Co.). Column chromatography was carried out with Cicareagent silica gel 60 N (spherical, particle size 63–210 mm). Thin-layer chromatography (TLC) was carried out with Merck TLC plates with silica gel 60 F254. Unless

Synthesis of benzo[d]imidazo[2,1-b]benzoselenoazoles: Cs₂CO₃-mediated cyclization of 1-(2-bromoaryl)benzimidazoles with selenium

• Mio Matsumura,
• Yuki Kitamura,
• Arisa Yamauchi,
• Yoshitaka Kanazawa,
• Yuki Murata,
• Tadashi Hyodo,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2019, 15, 2029–2035, doi:10.3762/bjoc.15.199

• reaction of 1a with sulfur or tellurium powder did not proceed, and the starting material 1a was recovered (Table 1, entries 17 and 18). The best result was obtained when 1a and Se powder were treated with Cs2CO3 in DMF under an argon atmosphere at 150 °C. The benzimidazo[2,1-b]benzoselenoazole product 2a

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• and electron-neutral organic guests [22][23][24][25][26][27][28][29][30][31]. In our previous study we have developed an efficient protocol to synthesize oxygen and sulfur-linked corona[m]arene[n]tetrazines from aromatic diol and dithiol derivatives and 3,6-dichlorotetrazine, respectively, in a simply

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia 10.3762/bjoc.15.186 Abstract A protocol of SO2F2-mediated installation of sulfonyl fluoride onto primary amides has been developed providing a new portal to sulfur(VI) fluoride exchange (SuFEx) click chemistry. The generated

• molecules contain pharmaceutically important amide and -SO2F moieties for application in the discovery of new therapeutics. Keywords: N-fluorosulfonyl amides; primary amides; sulfuryl fluoride (SO2F2); Introduction Sulfur(VI) fluoride exchange (SuFEx) is a new class of click chemistry developed by

Transient and intermediate carbocations in ruthenium tetroxide oxidation of saturated rings

• Manuel Pedrón,
• Laura Legnani,
• Maria-Assunta Chiacchio,
• Pierluigi Caramella,
• Tomás Tejero and
• Pedro Merino

Beilstein J. Org. Chem. 2019, 15, 1552–1562, doi:10.3762/bjoc.15.158

• tetrahydrofuran [45] have been experimentally reported as well as the oxidation of N-acylpyrrolidines to the corresponding lactams [46]. Admittedly, the oxidation of tetrahydrothiophene has been approached only computationally since in that case the sulfur atom would be more easily oxidized. Since the general