Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• -triisopropylsilyloxy-1,3-butadiene (48) gave compound 50 in 96% yield and 91% ee (Scheme 14). In 2006, Nishimoto and co-workers described an interesting application of a Diels–Alder reaction conducted, among others, in water and fluorous solvents [109]. Especially, the employment of water as solvent has gained great

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• thionation reactions, considerable efforts have been devoted to the improvement of the workup procedures of these reactions. For example, Soós and co-workers introduced perfluoroalkylated derivatives of LR, which simplified the product isolation via a fluorous reversed-phase solid extraction technique [9][10

• ]. This method with long perfluorinated alkyl chains is attractive in parallel synthesis and also in high-throughput biological screening. However, both the modified LR and the fluorous solvents are rather expensive and not practical for scaling up. Besides, basic aqueous solutions were utilized as well

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• fluorous interactions developed with the FC gas, we have selected various perfluoroalkyl chain lengths (C6F13, C7F15, and C8F17). The length of the (SG)n sequence was set to n = 5, which was found optimal in a previous report [28]. We synthetized three perfluoroalkylated double-chain peptide–lipid

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• into Class 2, of which applications should be strictly limited, particularly in pharmaceutical industry. To develop an environmentally benign alternative of this useful method, the reaction has been extended to green solvents such as water [16], fluorous solvents [17], supercritical CO2 [18], and very

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• a handle for the incorporation of a fluorous-tag for ease of purification by fluorous solid phase-extraction (FSPE). The use of the fluorous tag enables solution-phase automated synthesis of α-1,2-trimannose in the future as shown previously with a related spacer and fluorous tag [47]. Incorporation

• trichloroacetimidate mannosyl donors 3 and 4 [47][50] and the use of a fluorous tag containing an amino alcohol spacer rather than an alkene that would require late-stage modifications. The aminopentanol spacer 6 used at the reducing end to conjugate to the dendrimer was first protected with fluorous CbzF-NHS 5 to

• these conditions. Therefore, future applications to automated syntheses will exclude this nitrogen protecting group. The light chain fluorous CbzF tag was advantageous in reducing the number of steps to a readily conjugateable molecule for particle functionalization compared to that of our previously

Unexpected loss of stereoselectivity in glycosylation reactions during the synthesis of chondroitin sulfate oligosaccharides

• Teresa Mena-Barragán,
• José L. de Paz and
• Pedro M. Nieto

Beilstein J. Org. Chem. 2019, 15, 137–144, doi:10.3762/bjoc.15.14

• Teresa Mena-Barragan Jose L. de Paz Pedro M. Nieto Glycosystems Laboratory, Instituto de Investigaciones Químicas (IIQ), cicCartuja, CSIC and Universidad de Sevilla, Americo Vespucio, 49, 41092 Sevilla, Spain 10.3762/bjoc.15.14 Abstract Here, we present an exploratory study on the fluorous

• of a fluorous-assisted approach for the synthesis of CS oligosaccharides. The use of a fluorous tag allows the rapid isolation of fluorinated intermediates by performing a simple extraction from fluorous silica gel [27][28][29][30][31][32]. Moreover, this method maintains the advantages of solution

• intermediates by simple fluorous solid-phase extraction (F-SPE). Interestingly, the fluorous tag would be introduced by acylation using commercially available heptadecafluoroundecanoyl chloride and its deprotection would not involve any additional step at the end of the synthesis. N-Trifluoroacetyl (N-TFA

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

• trifluoromethyl radical, providing some selectivity to the process, which indicates that it could be applied to a guided LSF strategy. Itoh and co-workers have described a procedure for the direct C–H perfluoroalkylation of substrates, which can act as fluorous tags. The group utilised the corresponding

Syntheses, structures, and stabilities of aliphatic and aromatic fluorous iodine(I) and iodine(III) compounds: the role of iodine Lewis basicity

• Tathagata Mukherjee,
• Soumik Biswas,
• Andreas Ehnbom,
• Subrata K. Ghosh,
• Ibrahim El-Zoghbi,
• Nattamai Bhuvanesh,
• Hassan S. Bazzi and
• John A. Gladysz

Beilstein J. Org. Chem. 2017, 13, 2486–2501, doi:10.3762/bjoc.13.246

• . Box 23874, Doha, Qatar 10.3762/bjoc.13.246 Abstract The title molecules are sought in connection with various synthetic applications. The aliphatic fluorous alcohols RfnCH2OH (Rfn = CF3(CF2)n–1; n = 11, 13, 15) are converted to the triflates RfnCH2OTf (Tf2O, pyridine; 22–61%) and then to RfnCH2I (NaI

• , acetone; 58–69%). Subsequent reactions with NaOCl/HCl give iodine(III) dichlorides RfnCH2ICl2 (n = 11, 13; 33–81%), which slowly evolve Cl2. The ethereal fluorous alcohols CF3CF2CF2O(CF(CF3)CF2O)xCF(CF3)CH2OH (x = 2–5) are similarly converted to triflates and then to iodides, but efforts to generate the

• corresponding dichlorides fail. Substrates lacking a methylene group, RfnI, are also inert, but additions of TMSCl to bis(trifluoroacetates) RfnI(OCOCF3)2 appear to generate RfnICl2, which rapidly evolve Cl2. The aromatic fluorous iodides 1,3-Rf6C6H4I, 1,4-Rf6C6H4I, and 1,3-Rf10C6H4I are prepared from the

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

• to selectively “catch” the desired tetrasaccharide 153, which was rapidly separated from non-fluorinated impurities by fluorous solid-phase extraction (F-SPE). Subsequent release of the compound from the fluorous tag and F-SPE yielded pure 153 in 61% overall yield from donor 83. One potential side

Fluorinated cyclohexanes: Synthesis of amine building blocks of the all-cis 2,3,5,6-tetrafluorocyclohexylamine motif

• Tetiana Bykova,
• Nawaf Al-Maharik,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2017, 13, 728–733, doi:10.3762/bjoc.13.72

• , with intercalations between negative fluorous faces and positive protic faces of the rings. This was the case as can be seen from the packing structures in Figure 2. For compounds 13 and 14 intermolecular hydrogen bonding between the amide groups also contributes to this stacking structure but for

Organofluorine chemistry: Difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring

• Mathew J. Jones,
• Ricardo Callejo,
• Alexandra M. Z. Slawin,
• Michael Bühl and
• David O'Hagan

Beilstein J. Org. Chem. 2016, 12, 2823–2827, doi:10.3762/bjoc.12.281

• interaction of the positive non-fluorous face with the π-system of an aromatic ring by single crystal X-ray diffraction and NMR experiments. Additionally, the polarity of 4c has been calculated by computational optimisations. It follows that functionalised cyclohexanes containing the 1,3-di-CF2 motif would

Properties of PTFE tape as a semipermeable membrane in fluorous reactions

• Brendon A. Parsons,
• Olivia Lin Smith,
• Myeong Chae and
• Veljko Dragojlovic

Beilstein J. Org. Chem. 2015, 11, 980–993, doi:10.3762/bjoc.11.110

• PTFE fluorous structure. The solvent uptake effect, which was frequently observed in the course of PV-PTFE reactions, can be related to the surface tension of the solvent and the polarity of the solvent relative to the reagent. The lack of pores in bulk PTFE prevents solvents from altering its

• permeability and, therefore, bulk PTFE is impermeable to most solvents and reagents. However, bromine, which is soluble in liquid fluorous media, diffused through the bulk PTFE. A better understanding of the PTFE phase barrier will make it possible to further optimize the PV-PTFE reaction design. Keywords

• : perfluorinated solvents; phase screen; PTFE; semipermeable membrane; synthesis design; Introduction Fluorous reactions are a relatively new addition to the portfolio of synthetic methods [1][2][3][4][5]. In a fluorous triphasic reaction, introduced by Curran in 2001, a fluorous phase screen was used to

Cyclodextrin-grafted polymers functionalized with phosphanes: a new tool for aqueous organometallic catalysis

• Jonathan Potier,
• Stéphane Menuel,
• David Mathiron,
• Véronique Bonnet,
• Frédéric Hapiot and
• Eric Monflier

Beilstein J. Org. Chem. 2014, 10, 2642–2648, doi:10.3762/bjoc.10.276

• supercritical CO2, ionic liquids or fluorous phases have been used to immobilize the organometallic catalyst [3][4][5]. Co-solvents, surfactants, amphiphilic phosphanes, molecular receptors, polymers or dispersed particles have also been investigated to favour contacts between the aqueous and the organic

Supercritical carbon dioxide: a solvent like no other

• Jocelyn Peach and
• Julian Eastoe

Beilstein J. Org. Chem. 2014, 10, 1878–1895, doi:10.3762/bjoc.10.196

• identification of Lewis acid–base interactions as a mechanism for solubility in CO2 has given rise to many potentially CO2 soluble polymers, including oxygenated and acylated species [26][71][79][80]. The first non-fluorous polymers to be effectively designed and solubilised were poly(propylene glycol)-diol

One-pot synthesis of cyanohydrin derivatives from alkyl bromides via incorporation of two one-carbon components by consecutive radical/ionic reactions

• Shuhei Sumino,
• Akira Fusano,
• Hiroyuki Okai,
• Takahide Fukuyama and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2014, 10, 150–154, doi:10.3762/bjoc.10.12

• reaction conditions where a catalytic amount of fluorous tin hydride and an excess amount of sodium cyanoborohydride were used, initially formed aldehydes can be converted into hydroxymethylated compounds in one-pot [7][8][9], since borohydride acts not only as the reagent for the regeneration of tin

Synthesis of enantiomerically pure (2S,3S)-5,5,5-trifluoroisoleucine and (2R,3S)-5,5,5-trifluoro-allo-isoleucine

• Holger Erdbrink,
• Elisabeth K. Nyakatura,
• Susanne Huhmann,
• Ulla I. M. Gerling,
• Dieter Lentz,
• Beate Koksch and
• Constantin Czekelius

Beilstein J. Org. Chem. 2013, 9, 2009–2014, doi:10.3762/bjoc.9.236

• observed, this stability was mainly attributed to a higher hydrophobicity or the formation of a fluorous core [2][10]. Tirrell et al. found that the biological function of the helical GCN4 transcription factor can be retained, when utilizing racemic mixtures of 5,5,5-trifluoroisoleucine (5-F3Ile) as

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• of perfluorodecyldiphenylphosphine coordinate to palladium dichloride to form a catalytically active palladium complex that is useful for a fluorous/organic biphasic system. Cummins devised radical phosphination of bromobenzene or bromocyclohexane with white phosphorus by means of a trivalent

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• reported the application of the synthetically powerful Suzuki–Miyaura reaction within aqueous microdroplets buffered by catalytically active fluorous interfaces [45]. Images of the flow channels captured by a high-speed camera provided preliminary kinetic data by allowing the precipitation of the solid

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• unsaturated building blocks. The approach involved the iterative attachment of a propagating and a terminating building block to a fluorous-tagged initiating building block. Metathesis cascade chemistry was used to “reprogram” the molecular scaffolds. Remarkably, in one case, a cyclopropanation reaction

• competed with the expected metathesis cascade process. Finally, it was demonstrated that the metathesis products could be derivatised to yield the final products. At each stage, purification was facilitated by the presence of a fluorous-tagged protecting group. Keywords: alkaloids; cyclopropanes

• of metathesis substrates by iterative attachment of simple unsaturated building blocks to a fluorous-tagged linker 1 (e.g., → 2 or 3). Subsequently, metathesis cascade reactions were used to “reprogram” the molecular scaffolds, concomitantly releasing the products from the linker (e.g., → 4 or 5) [14

Recyclable fluorous cinchona alkaloid ester as a chiral promoter for asymmetric fluorination of β-ketoesters

• Wen-Bin Yi,
• Xin Huang,
• Zijuan Zhang,
• Dian-Rong Zhu,
• Chun Cai and
• Wei Zhang

Beilstein J. Org. Chem. 2012, 8, 1233–1240, doi:10.3762/bjoc.8.138

• , Boston, MA 02125, USA 10.3762/bjoc.8.138 Abstract A fluorous cinchona alkaloid ester has been developed as a chiral promoter for the asymmetric fluorination of β-ketoesters. It has comparable reactivity and selectivity to the nonfluorous versions of cinchona alkaloids and can be easily recovered from

• the reaction mixture by simple fluorous solid-phase extraction (F-SPE) and used for the next round of reaction without further purification. Keywords: asymmetric fluorination; β-ketoester; fluorous cinchona ester; organocatalysis; recyclable chiral promoter; Introduction Fluorinated organic

• supported cinchona alkaloids have been developed as recyclable chiral promoters or organocatalysts. Among them, the Cahard group developed soluble polymer- and ionic-liquid-supported cinchona alkaloids for electrophilic fluorination [21][22]. The Fache and Soόs groups developed fluorous tag-attached

Efficient and selective chemical transformations under flow conditions: The combination of supported catalysts and supercritical fluids

• M. Isabel Burguete,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2011, 7, 1347–1359, doi:10.3762/bjoc.7.159

• below the detection limit of 1 ppm [52]. c) Catalysts immobilized in other liquid phases Other unconventional solvents such as fluorous solvents, polyethyleneglycol (PEG) or water were also used in a manner similar to that described above for ILs [19]. An example is the hydrogenation of itaconic acid or

• acetamido acrylate by means of a chiral Rh catalyst based on a fluorous BINAPHOS ligand. In this case, the substrate and the product are dissolved in water while the liphophilic catalyst is maintained in a scCO2 phase, in a so-called inverted biphasic system [53][54]. A regime based on repetitive batch

• have shown a remarkable stability, with consistent results for at least 17 days of continuous operation. Conclusion The development of flow processes using scFs in combination with catalysts supported either on solid or liquid phases (ILs, PEG, fluorous phases, etc.) presents a large potential for

Synthesis of diverse dihydropyrimidine-related scaffolds by fluorous benzaldehyde-based Biginelli reaction and post-condensation modifications

• Bruno Piqani and
• Wei Zhang

Beilstein J. Org. Chem. 2011, 7, 1294–1298, doi:10.3762/bjoc.7.150

• achieved by conducting a multicomponent reaction for improved atom economy, under microwave heating for fast reaction, and with fluorous solid-phase extractions (F-SPE) for ease of purification. Keywords: Biginelli reaction; dihydropyrimidine; diversity-oriented synthesis; fluorous; Suzuki coupling

• intermediate for post-condensation reactions including cycloaddition, Liebeskind–Srogl reaction and Suzuki coupling to form three different heterocyclic skeletons. The high efficiency of the diversity-oriented synthesis was achieved by conducting fast, microwave-heated reactions and simple fluorous solid-phase

• extractions (F-SPE) for purification [7]. The perfluorooctanesulfonyl group served as a phase tag for F-SPE and also as a convertible linker for the Suzuki coupling to introduce biaryl functionality to the heterocyclic skeletons [8][9][10][11][12]. Result and Discussion Fluorous benzaldehydes 1 were prepared

Solvent-free phase-vanishing reactions with PTFE (Teflon^®) as a phase screen

• Kevin Pels and
• Veljko Dragojlovic

Beilstein J. Org. Chem. 2009, 5, No. 75, doi:10.3762/bjoc.5.75

• benefits in using heavier liquid perfluoro compounds as phase screens [19]. Gladysz used Teflon® tape to deliver and recover a fluorous catalyst [20]. Recently, we reported preliminary results on use of a solid perfluoro compound, PTFE (polytetrafluoroethylene, Teflon®) tape, as a phase screen between the