Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations

• Ian Walsh,
• Matthew S. F. Choo,
• Sim Lyn Chiin,
• Amelia Mak,
• Shi Jie Tay,
• Pauline M. Rudd,
• Yang Yuansheng,
• Andre Choo,
• Ho Ying Swan and
• Terry Nguyen-Khuong

Beilstein J. Org. Chem. 2020, 16, 2087–2099, doi:10.3762/bjoc.16.176

• inconsistency method with a cut-off threshold of 0.7, which was determined as achieving the same discrimination as manual classification on some test electropherograms. The data points presented to the clustering algorithm were an array of continuous signal intensities between migration time 2.9 and 4.1 (i.e

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• 41; a radical propagation pathway through the reduction of 18 was discounted, as the reaction required continuous irradiation. To further support this mechanistic hypothesis, we used ESIMS to identify the formation of the conjugated N-acyliminium 14a. The addition of 18 to allenamide 15 under the Ir

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• , Janssen-Cilag, S.A., C/ Jarama 75A, Toledo, Spain 10.3762/bjoc.16.159 Abstract The combination of supported ionic liquids and immobilized NHC–Pd–RuPhos led to active and more stable systems for the Negishi reaction under continuous flow conditions than those solely based on NHC–Pd–RuPhos. The fine tuning

• PdII. In this way, a “cocktail” of catalytic species, including molecular complexes, clusters and nanoparticles may be responsible for the catalytic activity [15]. In a continuous system, this can be accompanied by a significant leaching of the catalytic metal. In order to avoid a loss of activity by

• under continuous flow conditions. Results and Discussion Scheme 1 summarizes the synthetic approach used for the preparation of the functionalized polymers considered in this work. A commercially available PS-DVB bead-type macroporous chloromethylated polymer 1 (Merrifield resin with 20% DVB and 1.2

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• photochemical reactions due to the inherent lack of scalability issues as a consequence of the Beer–Lambert law of absorption. Consequently, continuous-flow chemistry represents one of the few ways in which pharmaceutically relevant quantities of compounds can be synthesized through photoinduced transformations

• ]. Targeting more sustainable protocols, a manganese catalyst was selected to trigger the coupling between an aryldiazonium salt and simple (hetero)aryls. A unique reactivity was obtained under irradiation with blue LEDs and a continuous-flow process allowed achieving higher reactivity. Under the optimized

• heteroarene coupling partners. Indeed, furans, thiophenes, and pyrroles underwent selectively the non-directed C–H functionalization, delivering a diversity of heteroaryl–aryl coupling products. Remarkably, the continuous-flow technique rendered this transformation perfectly suited for large-scale and rapid

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• with radioactively labeled substrates, the use of fluorescently labeled probes offers several advantages, including the continuous monitoring of the transport and a better time resolution. For reasons of comparison, the α-configured ᴅ-mannose probe MPC-3 was synthesized in parallel. The

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• this reaction under continuous flow using two catalytic beds. Finally, we emphasize that mechanistic insights on the catalytic conversion of biomass-derived platform molecules are required to make this value chain competitive with respect to the traditional synthesis of chemicals from fossil fuels. In

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• ribbons, and the associated sponge Spongia cf. agaricina (Demospongiae, Porifera), collected from Bunaken National Park (BNP, North Sulawesi, Indonesia). Nudibranchs and their egg ribbons revealed higher concentrations of the scalarane in comparison to the sponge, likely due to a continuous accumulation

Mechanochemical green synthesis of hyper-crosslinked cyclodextrin polymers

• Alberto Rubin Pedrazzo,
• Fabrizio Caldera,
• Marco Zanetti,
• Silvia Lucia Appleton,
• Nilesh Kumar Dhakar and
• Francesco Trotta

Beilstein J. Org. Chem. 2020, 16, 1554–1563, doi:10.3762/bjoc.16.127

• . Nanosponges, as a powder, could be used as excipients in tablets, capsules, suspensions and dispersions, and topical formulations [8]. The most common NS synthetic pathway consists in dissolving the chosen CD in a suitable solvent, under continuous stirring, and then adding the crosslinker followed by a

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

• Christopher G. Thomson Ai-Lan Lee Filipe Vilela Institute of Chemical Sciences, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS Scotland, United Kingdom 10.3762/bjoc.16.125 Abstract The synergy between photocatalysis and continuous flow chemical reactors

• irradiation. Herein, we review some important developments of heterogeneous photocatalytic materials and their application in flow reactors for sustainable organic synthesis. Further, the application of continuous flow heterogeneous photocatalysis in environmental remediation is briefly discussed to present

• demonstrated the safe use of gaseous CF3I as a reagent for the continuous flow PRC trifluoromethylation of 5-membered heterocycles, such as N-methylpyrrole (1, Scheme 1), with a high conversion and selectivity for the monofunctionalised product 2 [62]. The system achieved full conversion for a variety of

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• -membered keto ester derivatives did not show any desired reaction. In combination with a continuous-flow strategy, this disulfide-catalyzed aerobic oxidation process can be scaled up to a gram-scale. A plausible mechanism of the reaction is shown in Scheme 11. The hydroxylation starts with the formation of

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• batch-to-batch variability. Tubular reactors of solid reagents combined with solution-phase reagents enable the continuous-flow preparation of organomagnesium reagents. The use of stratified packed-bed columns of magnesium metal and lithium chloride for the synthesis of highly concentrated turbo

• , most probably due to the disaggregation of oligomers [43][44]. We used this approach to overcome the solubility issue under continuous conditions. First, we verified that similar results are achieved in presence and absence of LiCl in solution for the EtMgBr formation (Section 2.2, Supporting

• continuous and stable generation of iPrMgCl⋅LiCl (≈100 mmol) in the steady state under similar ODR prototype conditions. A certain volume of the starting material solution (6 mL) was discarded to prevent the dilution of iPrMgCl⋅LiCl at the beginning and at the end of the experiment due to solvent diffusion

Photocatalytic trifluoromethoxylation of arenes and heteroarenes in continuous-flow

• Alexander V. Nyuchev,
• Ting Wan,
• Borja Cendón,
• Carlo Sambiagio,
• Job J. C. Struijs,
• Michelle Ho,
• Moisés Gulías,
• Ying Wang and
• Timothy Noël

Beilstein J. Org. Chem. 2020, 16, 1305–1312, doi:10.3762/bjoc.16.111

• , Road, North Chicago, Illinois 60064, United States of America 10.3762/bjoc.16.111 Abstract The first example of photocatalytic trifluoromethoxylation of arenes and heteroarenes under continuous-flow conditions is described. Application of continuous-flow microreactor technology allowed to reduce the

• residence time up to 16 times in comparison to the batch procedure, while achieving similar or higher yields. In addition, the use of inorganic bases was demonstrated to increase the reaction yield under batch conditions. Keywords: C–H functionalization; continuous-flow; organic synthesis; photoredox

• photoredox protocols for the radical trifluoromethoxylation of unfunctionalized (hetero)arenes by using specifically designed CF3O radical-releasing agents (Scheme 1B). Following our long-standing interest in the development of continuous-flow approaches for C–H functionalization [18][26] and photochemical

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• mmol) and AN (5 mL, 76.33 mmol) in CH3CN (100 mL) was poured to a quartz Erlenmayer flask. The solution was purged with N2 for 30 min and then irradiated for 20 h with continuous stirring. After the irradiation, the solvent was removed on a rotary evaporator and the crude reaction mixture was

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• miscibility during the production process [78][94]. Ultrasonic spray pyrolysis (USP) The USP method for continuous preparation of meso- and macroporous carbon spheres was used by Skrabalak et al. Ultrasonically nebulization of a precursor solution (carbon source and inorganic salts) by a humidifier results in

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• source and a Q-ToF mass analyzer. Acetonitrile and methanol were used as solvents. Samples were introduced at a continuous flow of 0.2 mL/min, and nitrogen served both as the nebulizer gas and the dry gas. Infrared spectra were recorded on a Spectrum 100 Perkin-Elmer FTIR spectrophotometer, with a

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• conjugated photosensitizers show increasing potential in photocatalysis since they combine both photo- and electrochemical properties which can substitute available metalloorganic photocatalysts. Batch and continuous-flow approaches are presented highlighting the relevance of enabling technologies for the

• ) [1][2][3]. This effect limits the penetration of photons to only a short distance into the reaction vessel, provoking increases of the reaction time, photocatalyst loading, byproducts, overheating and so on. Notably, the use of continuous-flow reactors for photochemical applications allows us to

• continuous-flow photochemistry a sustainable alternative approach being applied already by the chemical and pharmaceutical industries. Porphyrinoid is the term given for a class of organic compounds containing four pyrrole rings connected by four methylene bridges, and include porphyrin, chlorin

A method to determine the correct photocatalyst concentration for photooxidation reactions conducted in continuous flow reactors

• Clemens R. Horn and
• Sylvain Gremetz

Beilstein J. Org. Chem. 2020, 16, 871–879, doi:10.3762/bjoc.16.78

• centered on the combination of light with continuous flow reactors [1][2][3][4][5][6]. The reason for this increased interest is that continuous flow photochemical reactors can overcome various limitations that occur when the same reaction run in batch reactors [7]. For example, the flow reactor can

Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K₂CO₃/n-Bu₄PBr in water

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati and
• Gregor Schnakenburg

Beilstein J. Org. Chem. 2020, 16, 778–790, doi:10.3762/bjoc.16.71

• broad substrate scope, functional group tolerance, and simple purification technique is highly desired. In our continuous effort of synthesizing indole derivatives [29][30][31], herein, we report an efficient synthesis of multiple halogen-substituted (1H-indol-3-yl)methanol derivatives in the presence

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• peroxide bridge, has been subject of extensive scientific investigations during the last decade [53][54][55][56][57][58][59][60][61][62][63]. In this context, Seeberger and co-workers successfully developed an ingenious continuous-flow process for the hemisynthesis of pure artemisinin from

• review also shed light on the continuous improvement of protocols relying on this reaction, potentially leading to tailorable properties of earmarked therapeutic agents. Intramolecular (A) and intermolecular (B) enyne metathesis reactions. Ene–yne and yne–ene mechanisms for intramolecular enyne

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• -2,3-Disubstituted butanediacetal derivatives of dimethyl tartrates 9–11 can be converted to cis-isomers 12–14 (Scheme 2) [32]. Compound 12 can be obtained from trans-dimethyl ester 9 in a two-step procedure either following a traditional way or using continuous flow chemistry [32][33][34]. The

A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• proceeded well using a catalytic amount of the synthesized catalyst 58 in water at 70 °C to create 1,4-disubstituted 1,2,3-triazole products in good to high yields (Scheme 9). In terms of recyclability, there was a continuous decrease in the catalytic activity of 58 from the first to the second to the third

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• synthesis of β-nitrate ester carboxamides using tert-butyl nitrite as the nitro source and oxygen as the oxidant through the ring opening of 2-oxazolines [9] (Scheme 1a). Kappe reported a two-step continuous-flow synthesis of N-(2-aminoethyl)acylamides through ring opening/hydrogenation of oxazolines with

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• moderate to good yields. Notably, alkyl iodides were also suitable substrates. The methodology proved to be compatible with a broad range of functional groups. To demonstrate the synthetic utility of the process, the reaction was developed under continuous flow conditions to afford an easy and

• synthesized in 57% yield. Importantly, the reaction scale was increased to 1 g under continuous flow conditions. Then, the reaction was extended to the cyclization of a stilbene derivative into phenanthrene in a moderate 23% isolated yield. To explain the reaction pathway, the authors suggested an oxidative

• mechanism. One year later, 2013, Collins and co-workers extended this concept to the synthesis of carbazole derivatives under continuous flow conditions (Scheme 30) [44]. Using, the [Cu(I)(dmp)(xantphos)]BF4 catalyst, the oxidative cyclization of various triarylamines was carried out in the presence of I2

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

• catalyst concentration by continuous regeneration of Cu(I) species using Cu(II) as starting material. These methods include initiators for continuous activator regeneration (ICAR) ATRP, activators regenerated by electron transfer (ARGET) ATRP, supplemental activators and reducing agent (SARA) ATRP, and

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• rapid redox reaction between the oxidant and the reducing agent instead of converting the substrate). Excitation of the photocatalyst, on the other hand, allows continuous formation of low concentrations of both oxidized and reduced radical forms of the substrate(s), and the excited catalysts (and/or