A chiral self-sorting photoresponsive coordination cage based on overcrowded alkenes

• Constantin Stuckhardt,
• Diederik Roke,
• Wojciech Danowski,
• Edwin Otten,
• Sander J. Wezenberg and
• Ben L. Feringa

Beilstein J. Org. Chem. 2019, 15, 2767–2773, doi:10.3762/bjoc.15.268

• formed revealing that a chiral self-sorting process takes place. In addition, two of the cage isomers can bind a tosylate anion in solution by formation of a host–guest complex. Results and Discussion Ligands Z-1 and E-1 (Scheme 1) were synthesized by a Suzuki cross-coupling reaction of 3

• -sorting. Next, we were interested in the guest binding abilities of cages Pd2(stable Z-1)4 and Pd2(stable E-1)4. The tosylate anion was chosen as it has the appropriate size to fit inside the cages. A Job plot analysis revealed a 1:1 binding stoichiometry between both cage isomers and OTs− (Figures S3–S5

• , Supporting Information File 1), which corresponds to the model in which OTs− serves as a guest molecule which is encapsulated inside the cages [55][56]. 1H NMR titrations with tetrabutylammonium tosylate revealed that both cages are able to bind OTs−, showing similar binding strengths (KB = 1604 ± 39 M−1 for

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• )-7 (Scheme 6) which was found to be an effective inhibitor of the mitotic kinesin. The biologically active enantiomer of mexiletine (R)-24 was efficiently synthesized from the alcohol (2R,1'R)-7 (Scheme 7) [45]. When the respective tosylate (2R,1'R)-25 was treated with 2,6-dimethylphenoxide two

• )-24 was obtained. On the other hand, alkylation of 2,6-dimethylphenol with the tosylate (2S,1'R)-25 proceeded regioselectively to give (2S,1'R)-26, a precursor to (S)-24. (−)-Cathinone ((S)-27) is an alkaloid acting as a central nervous system stimulant found in leaves of Catha edulis. It was

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• form alcohol 4 and further base-mediated alkylation with tosylate 5 affords phosphonate ester intermediate 6. Subsequent dealkylation of 6 using trimethylsilyl bromide (TMSBr) gives adefovir (1). The related analogue tenofovir, developed as an anti-HIV agent, may be prepared in a similar manner [37][38

• ]. The poor solubility of adenine and its derivatives in most organic solvents restricts the choice of solvent for this and subsequent reactions to polar aprotic solvents such as DMF, NMP and DMSO [38]. The choice of base for the alkylation of alcohol 4 with tosylate 5 has been the subject of recent

• tosylate 5 remained the superior alkylating agent under these conditions. The reaction of 4 with iodide 7 afforded only a trace amount of the phosphonate, with mostly unreacted starting material evident in the 1H and 31P NMR spectra of the crude reaction mixture. The reaction with triflate 8 resulted in a

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• synthesis may be partially explained by the fast mutarotation of 2′,3′-O-isopropylidene-D-ribofuranosylamine and its tosylate. This mutarotation is solvent-dependent. For example, according to 1H NMR data presented in the work of Cusack et al. [40], compound 23 exists essentially as the pure β-anomer in

• chloroform whereas in dimethyl sulfoxide and water solutions, mixtures of α- and β-anomers are observed, with α/β ratio being 1:1.7 and 1:1.5, respectively. Moreover, mutarotation of the tosylate 23 is very fast in aqueous basic solution, being almost instantaneous in aqueous 2 M Na2CO3 as emphasized by the

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• methyl tosylate (TsOCH3) as the methyl donor [72]. Kräutler et al. found an equilibrium methyl transfer between methylcobalamin and the methylated complex of 1 resulting in cob(II)alamin and β-methyl heptamethyl cob(III)yrinate. Such a thermal equilibration takes 16 days at room temperature [73]. Keese

Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria

• Luce Mattio,
• Loana Musso,
• Leonardo Scaglioni,
• Andrea Pinto,
• Piera Anna Martino and
• Sabrina Dallavalle

Beilstein J. Org. Chem. 2018, 14, 2482–2487, doi:10.3762/bjoc.14.224

• tosylate in the presence of 18-crown-6 ether [15]. The synthesis of benzyl tosylate was accomplished using benzyl alcohol and freshly recrystallized p-toluenesulfonyl chloride in the presence of anhydrous trimethylamine and DMAP, in anhydrous dichloromethane [25]. At this stage, all attempts to obtain the

• key intermediate 13 removing the p-methoxybenzyl group [24][26][27][28] from 11 failed. Finally, compound 13 was successfully obtained by modifying the sequence of reactions. Deprotection of compound 10 with TFA [24], followed by selective alkylation with benzyl tosylate as previously described

• to rt, 1 h, 8a: 81%, 8b: 66%; e) dodecanoyl chloride, TEA, CHCl3, 0 °C to rt, 3 h, 90%; f) t-BuOK 1 M in THF, THF, reflux, 1.5 h, 65%; g) benzyl tosylate, KHMDS 0.5 M in toluene, crown ether 18-crown-6, THF, 0 °C to rt, 3 h, 35%; h) TFA, 60 °C, 2h; i) CAN, CH3CN/H2O (3:1), 0 °C to rt, 1h; j) benzyl

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• pyridine or TEA was sluggish. Subsequent substitution of the tosylate in 8 either with Super-hydride® (LiBHEt3) or with a cuprate generated in situ from MeMgBr and CuI afforded pyrrolidines 9 [31] and 12 in 68% and 44% yield, respectively (Scheme 1). In the course of tosylate substitution with the cuprate

• , 3-methylpiperidine 11 was isolated as a byproduct in 32% yield. A formation of the piperidine 11 proceeds via opening of aziridinium intermediate 10 (Scheme 1) [32]. Interestingly, a product of a ring expansion was not observed during the tosylate substitution with LiBHEt3. Simple acidic hydrolysis

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• of the desired aryl moiety, and the ortho-effect exerted by the 2-amido substituent was expected to improve the chemoselectivity further. Salt 5a was synthesized in good yield using our reported arylboronic acid methodology [33] (Scheme 3). Attempts to form the corresponding tosylate salt, either

Imide arylation with aryl(TMP)iodonium tosylates

• Souradeep Basu,
• Alexander H. Sandtorv and
• David R. Stuart

Beilstein J. Org. Chem. 2018, 14, 1034–1038, doi:10.3762/bjoc.14.90

• (TMP)iodonium tosylate salts. The aryl transfer from the iodonium moiety occurs under electronic control with the electron-rich trimethoxyphenyl group acting as a competent dummy ligand. The yields of N-aryl phthalimides are moderate to high and the coupling reaction is compatible with electron

• reaction yield, using tosylate (OTs) produced the highest yield in both DCE and toluene as solvent (Table 1, entries 4–8). Given our ability to readily access aryl(TMP)iodonium tosylate salts [12] we continued our optimization with these reagents. We observed a very narrow operating temperature with a

• (via Mayr nucleophilicity constants) [16] may be useful in developing other coupling reactions with diaryliodonium electrophiles. Conclusion The coupling of both electron-deficient and sterically encumbered aryl groups with a phthalimide anion is achievable with aryl(TMP)iodonium tosylate salts. This

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• competing side reaction was the nucleophilic attack by the tosylate on the enolonium species 4. Only in the rare cases mentioned below homocoupling did take place. The enolonium species 4 (R1 = Ph, R2 = H) reacts readily with both electron-rich and electron-poor TMS enol ethers 5 (Scheme 2). Thus, the cross

• enolonium species leads it to react faster with the less-hindered tosylate despite its poor electronic nucleophilicity. Thus, when the strategy of converting the least hindered enolate into the enolonium species 4 is used even highly hindered TMS enol ethers 5 may be used with formation of tertiary carbon

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• achieved within 40 minutes at 25 Hz in the presence of ethyl acetate although the integrity of the vessel was compromised and significant levels of metallic copper were removed from the walls during work-up. Expeditious displacement of tosylate or halides from 5′-derivatised nucleosides was achieved using

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• proceed via an SN2 reaction of a cyclic intermediate such as I1, judging from the syn selectivity of the dioxytosylation [52][53]. The attack of the tosylate ion on I1 possibly takes place at the benzylic position or at the methylene carbon atom. The positive charge of I1 may be stabilized by the aryl

• styrene with 4a–e preferentially gave (S)-3, which forms via an electrophilic addition of the iodane toward the Si face of styrene, followed by an SN2 reaction with the tosylate ion. If an SN1 mechanism were involved in the oxytosylation of I1, the enantiomeric ratio of 3 would decrease owing to the

• planar structure of the benzylic cation. Thus, the tosylate ion may act as an effective nucleophile for the SN2 reaction of I1. The stereoface-differentiation in the dioxytosylation reaction using the lactate-derived aryl-λ3-iodanes is similar to that in preceding reactions [14], which include the

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• advantages of solution chemistry and solid-phase methods. Thus, solid-supported acyl chloride or pyridinium tosylate as the activator of nucleoside-3'-O-H-phosphonates/phosphoramidites, and polystyrene-bound trimethylammonium periodate as oxidation reagent have been demonstrated to be superior for dimer and

Diels–Alder cycloadditions of N-arylpyrroles via aryne intermediates using diaryliodonium salts

• Huangguan Chen,
• Jianwei Han and
• Limin Wang

Beilstein J. Org. Chem. 2018, 14, 354–363, doi:10.3762/bjoc.14.23

• cycloaddition reaction of 1-phenylpyrrole (1a) using phenyl(mesityl)iodonium tosylate (2a) as benzyne precursor. To our delight, with LiHMDS as the base in toluene, the Diels–Alder adduct 3aa was obtained in 23% yield at room temperature (Table 1, entry 1). However, when the reaction temperature was increased

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• extend the carbon chain by one atom. The alcohol 11 was first converted into the corresponding tosylate (Scheme 1), but when this tosylate was subsequently treated with cyanide the undesired disubstituted product 14 was formed in 40% yield. Unfortunately, despite varying the reaction stoichiometry it was

Solid-state mechanochemical ω-functionalization of poly(ethylene glycol)

• Michael Y. Malca,
• Pierre-Olivier Ferko,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2017, 13, 1963–1968, doi:10.3762/bjoc.13.191

• terminal group (Figure 1) [20]. The functionalization of mPEG was also corroborated by the observed shift in the 1H NMR signals of the tosylate group protons from 7.92 (2H) and 7.49 (2H) in TsCl to 7.79 and 7.34 ppm, in mPEG–OTs (Figure S1, Supporting Information File 1) [20]. Employing NaOH as a base

• mPEG with tosylate functionality. TsCl = p-toluenesulfonyl chloride; CEA = chloroethylamine·HCl; Mw = molecular weight. All reactions were ball-milled at an operating frequency of 30 Hz. Surveyed reactions of mechanochemical derivatization to afford mPEG–Br, –SH, –COOH and –NH2 derivatives. Supporting

Influence of the milling parameters on the nucleophilic substitution reaction of activated β-cyclodextrins

• László Jicsinszky,
• Kata Tuza,
• Giancarlo Cravotto,
• Andrea Porcheddu,
• Francesco Delogu and
• Evelina Colacino

Beilstein J. Org. Chem. 2017, 13, 1893–1899, doi:10.3762/bjoc.13.184

• mechanochemistry offers significant challenges. For instance, the molecular weight negatively affects the reaction design and is almost one order of magnitude higher here than for common organic molecules. The laborious preparation of the starting CD-tosylate [24][25], and the considerable reactant molecular mass

• ]. Despite the longer milling times, using less balls allow outcomes to be improved [14]. This work takes the above-mentioned results as a base from which to address the mechanochemical synthesis of 6I-monoazido-6I-monodeoxy-β-CD and 6I-S-monodeoxy-6I-monothiouronium-β-CD tosylate (TU-β-CD), an important CD

• intermediate for the preparation of 6I-S-monodeoxy-6I-monothio-β-CD [26]. Having selected the 6I-O-monotosyl-β-CD (Ts-β-CD) as the benchmark, the nucleophilic displacement of the tosylate group in the presence of azido or thiourea (TU) nucleophiles was chosen for the study under different milling conditions

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• resulting tosylate and subsequent epoxidation of the obtained tosyloxy alcohol with anhydrous K2CO3 in absolute ethanol (Scheme 10) provided compound 5. The NMR spectra and specific rotations of 5 also matched those reported in the literature [17][18][19][36]. Conclusion In summary, in the context of

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

• ′-tosylates in five to 60 minutes. Under these conditions, commonly-encountered nucleoside cyclisation byproducts (especially of purine nucleosides) were not observed. Liquid-assisted grinding of the same 5'-iodide and 5′-tosylate substrates with potassium selenocyanate in the presence of DMF produced the

• ball-milling chemistry on nucleoside substrates has not, to the authors’ knowledge, been demonstrated, despite reports of similar chemistry on glycoside derivatives [16][23] and α-amino acid analogues [24]. We describe here the efficient displacement of 5'-chloride, iodide or tosylate leaving groups

• -dependency also observed with KSeCN under Finkelstein conditions [38]. Finally, our approach also offers the convenience of employing tosylate and halide precursors rather than relying on the esoteric tresylate leaving group system. Model reactions of 5′-chloro-5′-deoxyadenosine (1a) with 4

Direct arylation catalysis with chloro[8-(dimesitylboryl)quinoline-κN]copper(I)

• Sem Raj Tamang and
• James D. Hoefelmeyer

Beilstein J. Org. Chem. 2016, 12, 2757–2762, doi:10.3762/bjoc.12.272

• , tosylate, or aryliodide (as Ar2I+)) using Pd-based catalysts. These methods achieve coupling of aryl C–C bonds with high activity and selectivity; however, the reactants are quite expensive and there is significant opportunity to improve the atom efficiency. Additionally, there is impetus to utilize less

• direct arylation reaction can be achieved with X = halogen, triflate, tosylate [14], B(OH)2 [15][16][17][18][19][20], SnR3 [21], Si(OR)3 [22], or with the use of aryliodonium salts [23]; wherein halogen atoms represent the most cost-effective and atom-efficient functional group. The reactions typically

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

• an sp3 carbon increased the yield of the transetherification reaction significantly. Attempts were also made to attach an alkyne to EDOT via the reaction between hydroxymethyl EDOT and propargyl tosylate using DABCO as catalyst, but it led to a very low yield and this EDOT-propargyl product was very

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• tosylate to yield compounds 5a,b in high yields of 87% and 81%, respectively. These derivatives can be utilized for both variants of the Staudinger ligation in addition to the classical and strain-promoted variants of the Huisgen-click reaction. For future radiolabeling procedures, nitro derivatives 4a and

• dried over Na2SO4 and the solvent was removed to yield 931 mg of compound 3b. Spectra are in agreement with those found in the literature [46]. 4-(But-3-yn-1-yl)-1-(4-nitrobenzoyl)piperazine (4a): Compound 3a (110 mg, 0.47 mmol), but-3-yn-1-yl tosylate (150 mg, 0.67 mmol) and Et3N (100 mg, 0.98 mmol

• -yn-1-yl)-1-(4-fluorobenzoyl)piperazine (4b): Compound 3b (70 mg, 0.34 mmol), but-3-yn-1-yl tosylate (90 mg, 0.40 mmol) and Et3N (51 mg, 0.50 mmol) were dissolved in anhydrous THF (6 mL) and the resulting mixture was stirred at 60 °C for 3 d. After reaction control by TLC, THF was changed by ethyl

Synthesis of medronic acid monoesters and their purification by high-performance countercurrent chromatography or by hydroxyapatite

• Elina Puljula,
• Jouko Vepsäläinen and
• Petri A. Turhanen

Beilstein J. Org. Chem. 2016, 12, 2145–2149, doi:10.3762/bjoc.12.204

• . Results and Discussion The synthesis of mixed tetraesters from the tetraalkylammonium salt of medronic acid trimethylester and alkyl tosylate utilizes a similar strategy used previously for the synthesis of monoesters (Scheme 2). The starting point for the synthesis was tetramethyl methylene-BP, from

• which one of the methyl groups was removed by selective demethylation with tributylamine. The resulting mono N,N,N,tributyl-N-methylammonium salt of the triester was then refluxed with the desired alkyl tosylate in acetonitrile. The resulting mixed tetraesters 2a–g were purified by column chromatography