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

• dealkylation and compatible with the presence of other groups such as allyl, ketone, primary alcohol, phthalimide, ester or thioether as illustrated with the transformation of the phosphonate 79 to the phosphonic acid 80 (Figure 23). The best results were obtained when 0.9 equivalents of BBr3 per phosphonate

• efficient reagent for the oxidation of phosphinic acid [244]. Diiodide in the presence of acid (HI) in water/ethanol solution yields the oxidation of the phosphinic acid 130 without oxidizing the thioether function [245] (Figure 36C). The Atherton–Todd conditions [246] (CCl4, NEt3, H2O) in the presence of

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• and nucleophilicity of the thioether aglycon [42][43][44]. Extensive studies on how to fine tune anomeric reactivities culminated in the establishment of the powerful reactivity-based chemoselective glycosylation method [11]. In this strategy, a thioglycosyl donor with high anomeric reactivity is

• added, which reacts with the intermediate to form the desired glycoside without the need for additional promoter. The resulting disaccharide bears a thioether aglycon, which can undergo another round of preactivation and glycosylation for rapid chain extension. As donor activation and acceptor

Ni nanoparticles on RGO as reusable heterogeneous catalyst: effect of Ni particle size and intermediate composite structures in C–S cross-coupling reaction

• Debasish Sengupta,
• Koushik Bhowmik,
• Goutam De and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 1796–1806, doi:10.3762/bjoc.13.174

• catalytic process has been established for the first time, and found to be best in the C–S cross-coupling reaction for Ni(0) and Ni(II) NPs of the average sizes 11–12 nm and 4 nm, respectively. Keywords: C–S cross-coupling; heterogeneous catalyst; Ni nanoparticle; reduced graphene oxide; thioether

• suppressing the overall yield of the thioether (Table 1, entries 5 and 6). Without using any base, the yield was 74%, while the use of KOH as a base afforded the thioether in 83% yield (Table 1, entries 7 and 8). Formation of the diphenyl disulfide via oxidative dimerization of benzenethiol was noticed (15

• Ni/RGO-60 under similar conditions affording the thioether in 91% and 84% yields, respectively (Table 1, entries 12 and 13). These observations suggest that both Ni/RGO-20 and Ni/RGO-40 with average Ni NPs size (≈10–11 nm) have better catalytic efficiency (yield 91–92%) than Ni/RGO-60 (≈17 nm

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

• reaction) [130]. Besides these alkyl- or aryl-thioether-forming reactions depicted in Scheme 14, also the introduction of a CF3S group to access trifluoromethylthioethers has been recently investigated [131]. In a very detailed study, Shen and co-workers have investigated the use of different cinchona

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• alkyl thiols in the presence of iPr2Net (Scheme 55) [99]. They showed that the coupled products, aryl pyridinethyl thioether and aryl alkyloxycarbonylethyl thioether, could be converted to aryl thiols under specified conditions, respectively. In 2010, the Hartwig group developed a Pd(OAc)2/CyPF-t-Bu

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• , has been reported in 2005 [6]. The studied Meldrum's acid derivatives 65 were functionalized at α- and/or β-positions by alkyl, haloalkyl, alkenyl, alkynyl, nitrile, ether, thioether, triisopropylsilyl (TIPS) or tert-butyldiphenylsilyl (TBDPS) groups. Depending on the type of catalyst and substrate, 1

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• the position of the methyl substituent from the para to the ortho or meta positions decreases the yield in toluene. Dimethylamino and thioether groups display a lower yield with method B (34b,g) contrary to the trifluoromethyl group (34i). With p-fluorobenzonitrile the decyanation is observed with

Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

• Olga Eguaogie,
• Patrick F. Conlon,
• Francesco Ravalico,
• Jamie S. T. Sweet,
• Thomas B. Elder,
• Louis P. Conway,
• Marc E. Lennon,
• David R. W. Hodgson and
• Joseph S. Vyle

Beilstein J. Org. Chem. 2017, 13, 87–92, doi:10.3762/bjoc.13.11

• We initially examined VBM-facilitated reactions of 5′-chloro-5′-deoxyadenosine (CldA, 1a) with 4-methoxybenzylthiol (MobSH) to generate the corresponding 5′-thioether (MobSdA, 2a) as a model system (Scheme 1). Despite the known reactions of 1a with aryl and alkyl chalcogenate salts [6], there is only

• halonucleoside and no additional handling was required during work-up of the thioether product (2a). Likewise, 5′-tosylthymidine (TsT, 1c) was rapidly consumed. Only in the case of IdT (1d) were any (minor) impurities observed when all reagents were added to the vessel prior to commencing VBM. These impurities

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• methylenethiol derivative EDOT-CH2SH [18], as nucleophiles, as well as the halomethyl derivative EDOT-CH2-Cl/Br [6][9] and the exomethylene-EDOT [19] as electrophiles, can be used to form ether, thioether, ester, amine and peptide linkages with the pendant groups. The polar reaction conditions required for their

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• the beginning gave almost equimolecular amounts of the thioether and the ether, although during time the ether converted into the desired product (Table 2, entry 9). The higher reactivity of the substrate bearing the more electron donating group suggests that the reaction takes place through a

• . A test carried out by reacting presynthetized ether 4,4'-(oxybis(ethane-1,1-diyl))bis(methylbenzene) (5b) with benzyl mercaptan (2a) showed indeed that the thioether is formed easily starting from these two molecules under the reaction conditions reported (Figure 4). The dependence of the reaction

Efficient mechanochemical synthesis of regioselective persubstituted cyclodextrins

• Laszlo Jicsinszky,
• Marina Caporaso,
• Katia Martina,
• Emanuela Calcio Gaudino and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2016, 12, 2364–2371, doi:10.3762/bjoc.12.230

• thioether (6) the residual DMF increases the product solubility in methylene chloride and precipitation with MeOH removes the unreacted 1-dodecanethiol (DDS), whereas the absence of DMF, together with the strong complex formed between DDS and the product, meant that the product isolation was more difficult

Cyclisation mechanisms in the biosynthesis of ribosomally synthesised and post-translationally modified peptides

• Andrew W. Truman

Beilstein J. Org. Chem. 2016, 12, 1250–1268, doi:10.3762/bjoc.12.120

• the RiPP, as they fundamentally change the shape of a molecule, which can be critical for receptor binding or for protection from proteolysis. Examples include amide bonds, heterocyclisation to form thiazolines or oxazolines [24] (Figure 2), oxidative carbon–carbon bond formation [25] and thioether

• suppresses bacterial spoilage. Lanthipeptides are characterised by meso-lanthionine (Lan) and (2S,3S,6R)-3-methyllanthionine (MeLan) residues. Lanthionine consist of two alanine residues linked via a thioether that connects their β-carbons, while MeLan contains an additional methyl group (Figure 4B). These

• acid (Figure 4C). This is formed by sequential Michael-type cyclisations [57][60], where a conventional lanthionine thioether is first formed by the attack of cysteine onto Dha. The resulting enolate then attacks another Dha residue to stereospecifically form the carbocycle (Figure 4D), and the

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• transformation, Chen and co-workers showed that squaramide 103 catalyzes the addition of thiols to N-acryloylbenzamides to access thioether 101c [49]. The authors found that exclusion of water by addition of 4 Å molecular sieves as a desiccant was essential for achieving good enantioselectivity. When the R2

• optimal reactivity and selectivity, each nucleophile required a slightly different chiral amine catalyst. Interestingly, vinylaniline 126f could also be added to enone 118 in moderate to good yield and with good enantioselectivity. N-Trifluoroacetyl-1,2-aminothiol (126d) reacted to give thioether products

1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

• Antonia Mielgo and
• Claudio Palomo

Beilstein J. Org. Chem. 2016, 12, 918–936, doi:10.3762/bjoc.12.90

• imidazolones to nitroalkenes are shown by the transformations depicted in Scheme 4. Thus, nucleophilic displacement of the thioether group gives access to various types of heterocycles of interest in medicinal chemistry [66][67] (i.e., imidazolidinones 19 and 20, 2-arylimidazolone 22, 2-aminoimidazolone 23 and

• for the preparation of organosulfur compounds render thioether derivatives [96][97], this approach provides products with a free thiol group such as the α-mercaptocarboxylic acid derivative 67 (Scheme 11). Additionally, these mercapto derivatives can also be S-alkylated by treatment with the

• corresponding halide in the presence of sodium hydride, giving thus access to thioether derivatives of type 68, which can also be converted into γ-lactams such as 69. On the other hand, experiments carried out with pyridyl and quinoylthiazolone substrates reveal that in these cases selectivity is higher than

(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers

• Giorgos Koutoulogenis,
• Nikolaos Kaplaneris and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48

• either of the nitro group or the thioether group. The same year Wang and co-workers reported the enantioselective synthesis of spiro-chromanone-thiochroman compounds 175 catalyzed by a bifunctional indane-based thiourea 176 (Scheme 57) [78]. The cascade is initiated by the sulfa-Michael addition of 2

Synthesis of Xenia diterpenoids and related metabolites isolated from marine organisms

• Tatjana Huber,
• Lara Weisheit and
• Thomas Magauer

Beilstein J. Org. Chem. 2015, 11, 2521–2539, doi:10.3762/bjoc.11.273

• cyclononene ring could be realized in quantitative yield, the low-yielding formation of the macrocyclic thioether reduced the overall efficiency of the presented synthetic route. Based on a similar strategy and using the corresponding Z-isomer of cyclization precursor 39, Oishi and co-workers reported a total

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

• process that requires Lewis acid activation using BF3·Et2O and TiF4. The method gives access to a range of α-fluorovinyl thioethers, some in high stereoselectivity with the Z-isomer predominating over the E-isomer. The α-fluorovinyl thioether motif has prospects as a steric and electronic mimetic of

• . 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

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

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

• discussions here will be limited to copper-mediated C–N-bond formation, as we find this to be a flexible and convenient method. Recent work in our laboratory has involved the N-arylation of MPTTFs, including both unsubstituted and thioether-substituted examples (Scheme 6 and Table 3). These materials have

• thioether-functionalised MPTTFs to be prepared, including the addition of large ethylene glycol-based substituents utilised in the preparation of rotaxanes and pseudorotaxanes. N-Arylation of MPTTFs is an area of increasing interest and can be achieved using a copper-mediated reaction. We have applied this

3α,5α-Cyclocholestan-6β-yl ethers as donors of the cholesterol moiety for the electrochemical synthesis of cholesterol glycoconjugates

• Aneta M. Tomkiel,
• Adam Biedrzycki,
• Jolanta Płoszyńska,
• Dorota Naróg,
• Andrzej Sobkowiak and
• Jacek W. Morzycki

Beilstein J. Org. Chem. 2015, 11, 162–168, doi:10.3762/bjoc.11.16

• relatively clean; the isomerization product, i.e., cholesteryl phenyl ether (12f), was obtained in 22% yield. It should be emphasized that the yield of 11 was even better than those obtained in analogous reactions of 3α,5α-cyclocholestan-6β-yl phenyl thioether (40%) and 3α,5α-cyclocholestan-6β-yl p-tolyl

• thioether (52%) which we had previously studied [4]. Now it seems to be clear that high efficiency in the generation of the mesomeric carbocation may be attributed to the 3α,5α-cyclocholestan-6β-yl moiety rather than to the presence of an arylthiol group at C-3 or C-6. This conclusion is supported by the

• fact that cholesteryl phenyl thioether proved to be a rather poor cholesteryl donor for the electrochemical reaction (12% yield). In contrast to the above, the reaction of 4-hydroxyphenyl i-cholesteryl ether 6g was messy and afforded only 9% of the desired glycoconjugate 11. The isomerization product

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• Lisa F. Becker Dennis H. Schwarz Gerhard Wenz Organic Macromolecular Chemistry, Saarland University, Campus C4.2, 66123 Saarbrücken, Germany 10.3762/bjoc.10.310 Abstract Methyl and ethyl thioether groups were introduced at all primary positions of α-, β-, and γ-cyclodextrin by nucleophilic

• full methylation of all secondary hydroxy groups of β-CD causes a significant drop of binding potential, while substitution at the primary site does not alter the binding potential or even increases it [20]. Especially substitution of all primary hydroxy groups by thioether groups gives rise to

• compounds with very high binding potentials due to the higher hydrophobicity of sulfur compared to oxygen [21][22][23]. The octa-substituted carboxyethyl thioether of γ-CD is already in use under the name sugammadex (Bridion®) for the reversal of neuromuscular blockade, making use of its extremely high

Synthesis and characterization of a new photoinduced switchable β-cyclodextrin dimer

• Florian Hamon,
• Claire Blaszkiewicz,
• Marie Buchotte,
• Estelle Banaszak-Léonard,
• Hervé Bricout,
• Sébastien Tilloy,
• Eric Monflier,
• Christine Cézard,
• Laurent Bouteiller,
• Christophe Len and
• Florence Djedaini-Pilard

Beilstein J. Org. Chem. 2014, 10, 2874–2885, doi:10.3762/bjoc.10.304

• to the guest molecules [9][10]. These cyclodextrins linked by ester [11], thioether [12][13][14][15][16], urea [17][18][19], or triazole [20] moieties have been previously described. In addition, aromatic azobenzenes are excellent candidates as molecular switch linkers as they have two forms, namely

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• use of silyl, stannyl and thioether groups is generally preferred, since these groups are typically cleaved off upon anodic oxidation. A number of intramolecular cyclizations of 23- and 24-type intermediates have been reported both in presence and absence of electroauxiliaries. In the course of their

Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

• Simon A. Herbert,
• Laura J. van Laeren,
• Dominic C. Castell and
• Gareth E. Arnott

Beilstein J. Org. Chem. 2014, 10, 2751–2755, doi:10.3762/bjoc.10.291

• reasoning being that these are structurally related to planar chiral ferrocenes [32][33][34] and should thus behave in a similar fashion. To date though, we had not been in a position to examine whether this hypothesis was true. However, with the synthesis of inherently chiral thioether oxazoline

• calixarenes 5–8, we noted their similarity to planar chiral thioether oxazoline ferrocene ligands (9 in Figure 1) already reported by Dai and co-workers [35]. We therefore initiated a pilot study with our inherently chiral calix[4]arenes, using the palladium-catalyzed Tsuji–Trost allylation reaction (Scheme 3

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• (1o) underwent the alkylation/C3–C2 migration sequence to give 2-(methylthio)tryptophan 3o in good yields (Table 3, entry 5). Remarkably, the presence of a thioether in the indole ring offers unique, site-specific handles that can be utilized for further functionalization of the tryptophan moiety