A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• , fluoromethylene acetals. In the course of preparing synthetic samples of trace impurities in the herbicide pyroxasulfone, we were confronted with the problem of generating a bis(aryloxy)fluoromethane. Our intended route to structure 1 (Scheme 1) required the oxidation of bis-thioether 2, derived in turn from

• , we completed the radical bromination of 4 to produce 3 (Scheme 5), which was used to deliver the penultimate bis-thioether 2, with oxidation to 1 giving the target impurity structure as anticipated, with a combined yield for the three transformations from 4 to 1 of 42%. The synthesis of 4 was also

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• between radicals was carried out, affording thioether derivative 132 (Scheme 46). It has been proved by UV–vis spectroscopy and TDDFT calculations that the EDA complex was formed between an electron-rich mercaptan anion and electron-deficient aryl halides. Most importantly, this approach can be

• and thiobenzoic acid (140) to form an EDA complex, providing thioether derivative 141 with DIPEA as an organic base additive (Scheme 49). This reaction offers a novel and simple approach for the synthesis of α-mercapto acid derivatives under mild reaction conditions and demonstrates strong

• compatibility to the functional group. In addition, a gram-scale reaction also gives the desired thioether product in a yield of 99%. The construction of C–B bonds The C–B bond can be converted into a wide range of other functional groups by the conversion of alkyl borane [70][71][72]. Hence, it has become

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• perfluoroalkylthiolation. Thus, 4-nitrobenzyl alcohol (2a) was reacted with 1.25 equivalents of BT-SC2F5 and 2 equivalents of NEt(iPr)2 in MeCN for 2 h at rt. The analysis of the crude reaction mixture by NMR revealed the formation of two products: the desired (pentafluoroethyl) thioether 3a in 78% NMR yield and a second

• be effectively suppressed by conducting the reaction at −40 °C. Under these conditions, the desired (pentafluoroethyl) thioether 3a was obtained in 99% NMR yield (91% isolated yield, Table 1, entry 2). At this stage, we were ready to evaluate the relative efficiency of different

• was observed upon increasing the RF chain length (Table 1, entries 2–5). For example, thionoester 8a was generated as a significant side product (26% NMR yield) when using BT-SC5F11, while thioether 9a and thionoester 10a were provided in almost equal amounts when BT-SC8F17 was reacted with 2a. The

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• testing a variety of reaction conditions. More complex biorelevant examples such as isatin derivatives were also suitable substrates, affording the corresponding spirocyclic derivatives, albeit in low yields (Scheme 21) [59]. Unfortunately, thioether and sulfone-based linkers were unsuitable in this

Synthesis of six-membered silacycles by borane-catalyzed double sila-Friedel–Crafts reaction

• Yafang Dong,
• Masahiko Sakai,
• Kazuto Fuji,
• Kohei Sekine and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2020, 16, 409–414, doi:10.3762/bjoc.16.39

• of phenothiasilin 3l that was obtained in 93% yield starting from diaryl thioether 1g. N-(Benzyl)methylamine-substituted diaryl thioether 1h was also transformed into phenothiasilin 3m in 58% yield. The corresponding six-membered silacycles were not formed using N-aryl-bridged biaryls as substrates

• . Synthetic methods of six-membered silacyclic compounds. Scope of dihydrosilanes. Conditions: a: conditions B (Table 1, entry 5); b: conditions A (Table 1, entry 3). Scope of diaryl ether and diaryl thioether derivatives. Conditions: a: conditions B (Table 1, entry 5); b: conditions A (Table 1, entry 3). c

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• for its ability to undergo ligand transfer reactions. Ethylene sulfide has also been used as precursor for the synthesis of phosphine ligands. Kuang et al. synthesized a thioether-functionalized pyridine-based diphosphine ligand starting from diphenylphosphine and ethylene sulfide (Scheme 9) [70

• ligands. Synthesis of diphosphine pyrrole ligands. Synthesis of 4,5-diazafluorenylphosphine ligands. Synthesis of thioether-containing pyridyldiphosphine ligands starting from ethylene sulfide and diphenylphosphine. Synthesis of monoterpene-derived phosphine pyridine ligands. Synthesis of N

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• alkenylation of indole with n-butylacrylate in the presence of thioether ligands [32]. In the context of C–H activation reactions, the catalyst of choice has mostly been Pd [33][34]. However, as part of the search for newer and more cost-efficient catalysts, other transition metals, such as Ru, have also been

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

• covalently conjugates thiol groups of cysteine residues in proteins or peptides by the thio-Michael addition to the double bond of the maleimide to form a corresponding succinimidyl thioether. Conjugation of the cysteine sulfhydryl group with maleimide moieties allows us to prepare the bioconjugates

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• . Cyclic thioether peptides have been found in the chemical skeletons of natural products and synthetic ones that display a wide variety of activities, including antibiotics [31], vascular cell adhesion molecule-1 antagonists [32] and anticardiolipin antibodies [33][34]. Two MBH adducts (2) (R = Me, heptyl

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

• Zhen Cao Aline Lacoudre Cybille Rossy Brigitte Bibal Université de Bordeaux, Institut des Sciences Moléculaires, UMR CNRS 5255, 351 cours de la libération, 33405 Talence, France 10.3762/bjoc.15.239 Abstract The bis-ortho-thioether 9,10-bis[(o-methylthio)phenyl]anthracene was synthesized as a syn

• -atropisomer, as revealed by X-ray diffraction. This alkylaryl thioether ligand (L) formed different macrocyclic complexes by coordination with silver(I) salts depending on the nature of the anion: M2L2 for AgOTf and AgOTFA, M6L4 for AgNO3. A discrete M2L complex was obtained in the presence of bulky PPh3AgOTf

• ; homogeneous catalysis; prochiral; silver complex; thioether ligand; Introduction Since the early advances in the late eighties [1][2][3][4][5][6][7][8][9][10], silver(I) catalysis has been widely exploited based on the versatile redox and soft Lewis acid properties of this coinage metal cation. Silver

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

• thioether donor groups. Results and Discussion Firstly, a series of triarylmethylium salts with variable number of para-methoxy substituents was synthesized. The easily achievable cations (TMP)3C+, (DMP)(TMP)2C+ and (DMP)2(TMP)C+ (Scheme 1) were prepared by their respective literature procedures [18][31

• disubstituted thioether carbenium salts (2 and 3), it was possible to isolate the derivatives S2-TOTA+ (8) and S1-TOTA+ (9), respectively as their hexafluorophosphate salts (Scheme 4). The two Sx-TOTA+ derivatives were obtained with good yield after purification by column chromatography and subsequent

• triarylmethylium ions via SNAr reactions was demonstrated. These new thioether-substituted triarylmethylium ions provide access to a broad range of new heterocyclic carbenium dyes of the xanthenium, acridinium and triangulenium type via further SNAr reactions with primary amines and ring-closure reactions. The

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

• -difluoroethyl thioether motif to explore further its potential as a substituent for bioactives discovery chemistry. Incubation of two aryl–SCF2CH3 ethers with the model yeast organism Cunninghamella elegans, indicates that the sulfur of the thioether is rapidly converted to the corresponding sulfoxide, and then

• into diethyl ether and dichloromethane (DCM) and then carrying out HPLC analyses. Incubation of thioether 4 with C. elegans led to the identification of three metabolites 6–8 as illustrated in Scheme 1. These were isolated by semi-preparative HPLC. Two of these (6 and 7) displayed an AB system in the

• of sulfoxide 7 was also confirmed by X-ray structure analysis. The incubation of 4 in C. elegans, and then HPLC purification, was repeated three times all with very similar results. These incubations showed full conversion into the metabolites, and no starting thioether 4 was observed by NMR or HPLC

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• present several advantages compared to natural and synthetic glycolipids, linked by a chemically and enzymatically non-stable acetal function. Owing to their straightforward access, and the stability of thioether conjugates, 1-thio-β--glucopyranose (1a, Figure 1), and 2-acetamido-2-deoxy-1-thio-β

• apparition of new signals corresponding to the new anomeric protons (δH = 5.26 ppm) and the α-CH2 of the thioether bond (δH = 1.70 ppm). Compound 8 was isolated by column chromatography in 75% yield and no traces of starting material 6 were found. In addition, no intramolecular addition products neither mono

Azologization of serotonin 5-HT₃ receptor antagonists

• Karin Rustler,
• Galyna Maleeva,
• Piotr Bregestovski and
• Burkhard König

Beilstein J. Org. Chem. 2019, 15, 780–788, doi:10.3762/bjoc.15.74

• direct “azologization” [59] of reported non-photochromic antagonists [60][61] via replacement of the benzene-ring connecting amide bond and thioether, respectively, by an azo bridge. Results and Discussion Design and synthesis of azobenzene-based photochromic modulators The reported [60][61] scaffolds of

• 5-HT3R antagonists are based on an aromatic system either connected to a purine/pyrimidine moiety via a thioether bridge or a quinoxaline moiety via an amide bond. Referring to this work performed by the groups of DiMauro [60] and Jensen [61], we envisioned that the replacement of the thioether or

• properties of direct azologization to azo-extension, two additional derivatives of the in vitro most promising naphthalene azopurine 16c were synthesized either by keeping the original thioether (Scheme 5) or replacing it by an amide bond (Scheme 6) known as common structural feature of 5-HT3R antagonists

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• ], thioether macrocycles [11], macrocyclic Schiff bases [12] or even poly(phthalaldehyde) polymers [13]; taking into account that few studies were carried out with modified OPA on position 3 or 4. This could probably be due to the fact that the synthesis of 4-substituted OPA was, to the best of our knowledge

N-Arylphenothiazines as strong donors for photoredox catalysis – pushing the frontiers of nucleophilic addition of alcohols to alkenes

• Fabienne Speck,
• David Rombach and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 52–59, doi:10.3762/bjoc.15.5

• electron-donating substituents shifts the potentials correspondingly towards lower reduction potentials, as expected. By introducing the thioether substituent (see 4) to the arene the potential drops to about E(4+·/4) = 0.71 V (vs SCE). If the steric bulk is enhanced by a mesityl substituent (see 5) the

Synthesis and post-functionalization of alternate-linked-meta-para-[2ⁿ.1ⁿ]thiacyclophanes

• Wout De Leger,
• Koen Adriaensen,
• Koen Robeyns,
• Luc Van Meervelt,
• Joice Thomas,
• Björn Meijers,
• Mario Smet and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2190–2197, doi:10.3762/bjoc.14.192

• cyclophanes is formed by thiacyclophanes, in which the thioether linkages impose less conformational strain and which have an increased cavity size compared to other (oxa/aza)cyclophanes. Thiacalix[n]arenes are among the most widely known thiacyclophanes with significant ability for molecular recognition [5

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• chemistry. The formation of the thioether is also quite interesting, due to the possibility of accessing sulfones, which are abundant in drugs and drug-like molecules. The scope of the reaction covers the basics in terms of substituents on both reactants and investigates various substitution patterns. Most

Water-soluble SNS cationic palladium(II) complexes and their Suzuki–Miyaura cross-coupling reactions in aqueous medium

• Alphonse Fiebor,
• Richard Tia,
• Banothile C. E. Makhubela and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1859–1870, doi:10.3762/bjoc.14.160

• protons as opposed to the appearance of the corresponding protons in the ligand as a singlet at δH 4.29 integrating for four protons. In a similar fashion, complex 17b was synthesised and characterised successfully while ligands 19c and 19d possessing the electron-donating thioether side groups favoured

• attached to the sulfur atom are pointing away from the plane of the metal centre such that the thioether angles are 100.2(2)° and 102.72(2)° corresponding to C(6)–S(1)–C(9) and C(7)–S(2)–C(13), respectively. The thioether C–S bond lengths obtained are 1.808(4) Å and 1.816(4) Å for S(1)–C(6) and S(2)–C(7

• ), respectively. The thioether bond lengths and angles were found to be consistent to the reported data of 1.816 Å and 100.75°, respectively, by Sogukomerogullari et al. [39]. Similarly, the Pd–Cl bond length of 17d (2.3044(10) Å) also corresponds to that of square planar complexes with a chlorine ligand reported

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• the reaction between a phosphorothioate derivative and 2-bromo-4’-hydroxyacetophenone to produce a phosphate protected with a thioether-enol phosphotriester, phenol substituted (TEEP, Scheme 19) [77]. The TEEP modification was introduced into “active sites” of 8–17 and 10–23 DNAzymes with good yields

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• iodomethane in acetone in the presence of potassium carbonate to give methyl thioether 188 which provided hydrazinopyrazolo[3,4-d]pyrimidines 189 on treatment with an excess of hydrazine hydrate in ethanol. The hydrazine derivative 189 thus obtained was made to react with several carbonyl compounds like

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• reagent, trifluoromethyl-substituted sulfonium ylide, which was prepared by a Rh-catalyzed carbenoid addition to trifluoromethyl thioether (Scheme 4). This process was conducted in dichloromethane at 40 °C for 4 h with a catalyst loading of 100 ppm. Moreover, this new reagent was easily scaled-up and

A Brønsted base-promoted diastereoselective dimerization of azlactones

• Danielle L. J. Pinheiro,
• Gabriel M. F. Batista,
• Pedro P. de Castro,
• Leonã S. Flores,
• Gustavo F. S. Andrade and
• Giovanni W. Amarante

Beilstein J. Org. Chem. 2017, 13, 2663–2670, doi:10.3762/bjoc.13.264

• desired products in excellent yields and with up to dr >19:1 (products 2c, 2d and 2h). Substrates bearing an alkyl chain as an R1 group were well tolerated (2a and 2b). Importantly, azlactones containing a thioether or allyl substituents could be also accessed in good isolated yields (2f and 2g). The

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• propargylamine 7p is not stable under the conditions, which are necessary to cleave the thioether [100][101]. Synthesis of propargylamines with basic functional groups in the side chain Very often, basic amino acids, like lysine or arginine are found in the catalytic center of enzymes. Therefore, propargylamines