Grip on complexity in chemical reaction networks

• Albert S. Y. Wong and
• Wilhelm T. S. Huck

Beilstein J. Org. Chem. 2017, 13, 1486–1497, doi:10.3762/bjoc.13.147

• enzymatic reactions as a starting point to test the implementation of our design strategy. A more recent example of a chemical network capable of auto-amplification using thiols and thioesters (Figure 8) provides the ultimate proof that complex molecular systems can be designed “from scratch” [101]. Future

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• transglycosylations are available in a review by Nogushi, et al. [70]. 4.1.2 Synthesis of glycosyl azides, dithiocarbamates, and thiols: Shoda and colleagues have also shown that when using similar conditions to those described above in the presence of certain nucleophiles glycosyl azides [73], dithiocarbamates [74

• ], and aryl thiols [75][76] can be formed in moderate to quantitative yield with the 1,2-trans diastereomer prevailing in all instances (Scheme 23) (also partially reviewed in Noguchi et al. [70]). The substrate scope was extensive in all instances and included successful glycosylation of up to

• applications and we highlight these examples below. In 2016, the Rademann group could obtain 2-deoxy-2-N-acetyl glycosyl thiols using DMC, NEt3, and either BzSH or AcSH (Scheme 25) [80]. The authors noticed that the reaction proceeds through the detected oxazoline intermediate to provide solely the β-glycosyl

Phosphorus pentasulfide mediated conversion of organic thiocyanates to thiols

• Chandra Kant Maurya,
• Avik Mazumder and
• Pradeep Kumar Gupta

Beilstein J. Org. Chem. 2017, 13, 1184–1188, doi:10.3762/bjoc.13.117

• /bjoc.13.117 Abstract In this paper we report an efficient and mild procedure for the conversion of organic thiocyanates to thiols in the presence of phosphorus pentasulfide (P2S5) in refluxing toluene. The method avoids the use of expensive and hazardous transition metals and harsh reducing agents, as

• required by reported methods, and provides an attractive alternative to the existing methods for the conversion of organic thiocyanates to thiols. Keywords: dithiocarbamate; phosphorus pentasulfide; thiocyanate; thiol; toluene; Introduction Thiols constitute an important group of sulfur-containing

• compounds. They have a specific odour and often used as gas odorants in many industrial applications [1][2]. They occur as flavouring compounds in several fruits and spices and are found in a variety of enzymes at their active sites [3]. Thiols are produced by the wood-pulping industry, manure & sewer

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• and as effective tool in the immunological field). Review Synthesis of glyco-gold nanoparticles Despite the great inertness of this noble metal, Au can form stable bonds with sulfur-containing compounds (i.e., thiols or disulfides) [9][10] and it is possible to easily and robustly functionalize AuNPs

Sulfamide chemistry applied to the functionalization of self-assembled monolayers on gold surfaces

• Loïc Pantaine,
• Vincent Humblot,
• Vincent Coeffard and
• Anne Vallée

Beilstein J. Org. Chem. 2017, 13, 648–658, doi:10.3762/bjoc.13.64

• developed on gold surfaces. One of the main reasons could be explained by the necessity to work under mild conditions; it is well known that the energy of interaction between sulfur and gold is in order of 45–50 kcal/mol and the desorption of the thiols can occur at about 70 °C in hydrocarbon solvent [53

• . However, to be sure that no thiols were desorbed during the hydrolysis, the Sbound/Au4f signal ratio before and after the hydrolysis is compared and is quite similar (e.g. 0,034 and 0.032, respectively). We concluded that the hydrolysis process did not induce any desorption of thiols but may have modified

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

• Yajun Liu Shasha Liu Yan Xiao College of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China Department of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China 10.3762/bjoc.13.58 Abstract Phenols and aryl thiols are fundamental

• building blocks in organic synthesis and final products with interesting biological activities. Over the past decades, substantial progress has been made in transition-metal-catalyzed coupling reactions, which resulted in the emergence of new methods for the synthesis of phenols and aryl thiols. Aryl

• halides have been extensively studied as substrates for the synthesis of phenols and aryl thiols. In very recent years, C–H activation represents a powerful strategy for the construction of functionalized phenols directly from various arenes. However, the synthesis of aryl thiols through C–H activation

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

• reported a metal-free photocatalytic aerobic oxidation of thiols to disulfides under continuous-flow conditions [64]. Disulfides are useful molecules employed as drugs, anti-oxidants or pesticides as well as rubber vulcanizating agents [65]. Symmetric disulfides are generally obtained by oxidative coupling

• of thiols [66]. Noël and co-workers set up a microflow system equipped with a mass flow controller (MFC) able to introduce pure oxygen as the oxidant to oxidize a solution of thiol containing 1% of Eosin Y. The flow stream was exposed to white LED light in order to activate the reaction, and a

• dilution with pure EtOH was needed at the output to avoid clogging (Scheme 12). The residence time of 20 min guaranteed a limited irradiation time and high purity of the products. The disulfides were obtained with excellent yields, and the process was executed on challenging thiols as in the case of

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• dehydroalanine [6][7], ketones, aldehydes [8][9], carboxylic acids [8][9], amines [8][9][10], thiols [8][9], alcohols [11], epoxides [12], terminal alkynes [13][14] and azides [15] can be targeted to introduce a label. Such labels might increase the visibility in UV or MS detection in liquid chromatography

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

• Federica Santoro Matteo Mariani Federica Zaccheria Rinaldo Psaro Nicoletta Ravasio CNR ISTM, via C. Golgi 19, 20133 Milano, Italy 10.3762/bjoc.12.259 Abstract The synthesis of thioethers starting from alcohols and thiols in the presence of amorphous solid acid catalysts is reported. A silica

• the green chemistry point of view would be the direct substitution of alcohols (that are also available at low cost) with thiols. In this case the only byproduct will be water. However, due to the lack of a good leaving group the use of an acid catalyst is mandatory. Both Brønsted and Lewis acids can

• ] dispersed on silica is active in promoting the substitution of adamantanol, cinnamyl and benzyl alcohols with thiols whereupon significative amounts of Zr salt are required; whereas Wu and Han have shown that Ga(OTf)3 is an effective catalyst for the substitution of a wide range of benzylic and allylic

Synthesis of three-dimensional porous hyper-crosslinked polymers via thiol–yne reaction

• Mathias Lang,
• Alexandra Schade and
• Stefan Bräse

Beilstein J. Org. Chem. 2016, 12, 2570–2576, doi:10.3762/bjoc.12.252

• thiols, respectively. However, these characteristic bands are nearly extinguished in the IR spectra of the HCPs showing a high ratio of crosslinking for these reactions. In addition, the vibration bands of the HCPs at 3000 cm−1 correspond to the presence of olefinic bonds, which is in accordance to a

Et₃B-mediated and palladium-catalyzed direct allylation of β-dicarbonyl compounds with Morita–Baylis–Hillman alcohols

• Ahlem Abidi,
• Yosra Oueslati and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2402–2409, doi:10.3762/bjoc.12.234

• , amines and thiols. Experimental General IR spectra were recorded on a Bruker IFS 66v/S spectrometer. 1H NMR and 13C NMR spectra were recorded either on a Bruker AC-300 spectrometer (300 MHz for 1H and 75 MHz for 13C) in CDCl3, using TMS as an internal standard (chemical shifts in δ values, J in Hz). Mass

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

• thiouronium salt of CDs thiols can readily be obtained under aqueous basic conditions. Thioureido-CDs are crystalline compounds that are readily soluble in water, easy to purify and convert to thiols [8]. These intermediates can be efficiently prepared via the reaction of a TU excess (2–3 mol TU/halogen) and

• (entries 22, 23, and 26–28 in Table 1) despite the use of the considerably milder and safer base, potassium tert-butoxide (KOt-Bu). Our first target was to investigate the reaction between a good nucleophile (sulfur) and per-halogenated CDs. The TU method is widely used in the synthesis of various thiols

• and thioester compounds [8][30] and the CD thiouronium salt intermediates are not isolated [8] despite their good crystallization properties, while the excess/residual TU and used solvents are removed upon the conversion to thiols only. However, the easy crystallization of these salts is a nice

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• , incorporated into oligonucleotides by standard solid–phase synthesis and reacted with the desired molecules on the oligonucleotide level. As amines and thiols are among the widely used groups introduced for the post-synthetic modifications, the acyclic threoninol linker (2-amino-1,3-butanediol) [14][15][16][17

Solvent-free synthesis of novel para-menthane-3,8-diol ester derivatives from citronellal using a polymer-supported scandium triflate catalyst

• Lubabalo Mafu,
• Ben Zeelie and
• Paul Watts

Beilstein J. Org. Chem. 2016, 12, 2046–2054, doi:10.3762/bjoc.12.193

• of alcohols, thiols and amines is a fundamental reaction in organic synthesis. It is mostly used to protect these functional groups in multi-step synthesis processes. The acylation reaction is typically carried-out with activated carboxylic acid derivatives such as acid anhydrides [5], acyl halides

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• luciferin scaffolds [2][5][8]. Even in the presence of other thiols and amines, CBTs react rapidly and selectively with 1,2-aminothiols under physiological conditions. This selective and bioorthogonal reactivity of CBTs has been exploited in the development of the CBT ligation as a useful and fast

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• photooxidations of citronellol [35][40][41][42], indanes [43], monoterpenes [36], furans [42], furfurals [44], thiols [37] and amines [45] as well as the syntheses of ascaridol [46] and artemisinin [47]. Related microreactor setups were applied to biphasic gas/liquid mixtures in the photochlorination of

Organic chemistry meets polymers, nanoscience, therapeutics and diagnostics

• Vincent M. Rotello

Beilstein J. Org. Chem. 2016, 12, 1638–1646, doi:10.3762/bjoc.12.161

• nucleic acids, where we showed that cationic nanoparticles could bind to anionic DNA and inhibit transcription [37]. We also developed a number of strategies for delivery of small molecules, including glutathione-mediated release of covalently attached thiols [38], as the effective release of drugs

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• bifunctional molecules substituted by amines, thiols, carboxylates, sulfonates, phosphonates or bisphosphonates [5][6][7]. Particularly, a strong interaction between the NPs and the phosphonic moiety was observed and more interestingly the best results were obtained with bisphosphonate products [8][9]. For 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

• -workers explored the ability of chiral tertiary amines to catalyze the enantioselective addition of thiols to α-aminoacrylates (Scheme 5) [22]. The authors found that quinidine (21) catalyzed the enantioselective addition of benzylmercaptan (19) to α-aminoacrylate 20 in modest enantioselectivity

• to the enantioselective addition of aromatic thiols to 2-phthalimidoacrylates 29 in high yield and good enantioselectivity (Scheme 7) [24]. A variety of electron rich, neutral, and poor thiols coupled efficiently. Impressively, the aromatic thiol 28 could be substituted with hydroxy and amino groups

• reported the enantioselective conjugate addition of thiols to unactivated α-substituted acrylates followed by enantioselective protonation (Scheme 9) [28]. To overcome the low inherent electrophilicity of 38, the authors postulated that bifunctional iminophosphoran (BIMP) organocatalysts with increased

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

• and to tertiary thiols and thioethers in the case of thiazolones. In the future, other Brønsted base or bifunctional catalyst promoted reactions with these compounds can be envisaged. Some α-substituted heterocycles for asymmetric catalysis, their reactivity patterns against enolization, and resulting

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

• the Sonogashira reaction, which requires modified non-natural amino acids [32][33]. In 2013, our group reported the alkynylation of thiols using the hypervalent iodine reagent TIPS-EBX (1a, 1-[(triisopropylsilyl)ethynyl]-1,2-benziodoxol-3(1H)-one) (Scheme 1A) [34]. The reaction was almost

• instantaneous. It was highly chemoselective for thiols in the presence of other nucleophilic functional groups. The alkynylation could be therefore applied to cysteine-containing peptides. The scope of the reaction could be later extended to a broad range of aliphatic and aromatic alkynes [35]. In 2015, the

• efficiency of the reaction for the functionalization of proteins both in cell lysates and in the living cell was finally demonstrated [36]. Even if the alkynylation of cysteines is an important method, thiols are often part of disulfide bonds in folded proteins, and therefore difficult to access. Reduction

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

• (corresponding thiols or acetonitrile) were elaborated. Of particular interest is the introduction of a fluorine atom into the molecule of the biologically active compound. The introduction of a highly electronegative centre can lead to an increase in stability and changes in lipophilicity. Furthermore, it

Supported bifunctional thioureas as recoverable and reusable catalysts for enantioselective nitro-Michael reactions

• José M. Andrés,
• Miriam Ceballos,
• Alicia Maestro,
• Isabel Sanz and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2016, 12, 628–635, doi:10.3762/bjoc.12.61

• [12]. Cinchona-derived thioureas have been also prepared by co-polymerization of polyfunctionalized thiols with olefins [23]. Our interest in the search for novel bifunctional thioureas as organocatalysts [24][25][26][27] lead us to consider the preparation of different polymeric materials decorated

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• recently inspired to use the (de-Me-DHQ)2PHAL catalyst HCPD-44 in the addition of α-substituted nitro acetates 43 also into nitroolefins 41 (Scheme 11b) [43][44][45][46]. In a fascinating report, Melchiorre and co-workers use the 9-amino-CPD system CPD-48 to control the Michael addition of thiols 46 into α

Optimized methods for preparation of 6^I-(ω-sulfanyl-alkylene-sulfanyl)-β-cyclodextrin derivatives

• Eva Bednářová,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2016, 12, 349–352, doi:10.3762/bjoc.12.38

• and repeating units (ethylene glycol or methylene). The target compounds were characterized by IR, MS and NMR spectra. A simple method for their complete conversion to the corresponding disulfides as well as a method for the reduction of the disulfides back to the thiols is presented. Both, thiols and

• disulfides are derivatives usable for well-defined covalent attachment of cyclodextrin to gold or polydopamine-coated solid surfaces. Keywords: cyclodextrins; disulfides; monosubstituted derivatives; thiols; Introduction Cyclodextrins (CDs) [1], cyclic oligomers of α-D-glucopyranose, are used for their

• are much more stable alternatives to the thiols for a longer storage. That is why a method to recover the thiols from the disulfides was also studied. Results and Discussion For the preparation of the starting compound for all syntheses – Ts-β-CD (1) – we recently described [17] a modification of one