Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• feedstocks, and scalability up to gram scales in continuous flow. This review provides comparisons between the two techniques (multi-photon photoredox catalysis and PEC) to help the reader to fully understand their similarities, differences and potential applications and to therefore choose which method is

• standardization but also thanks to developments in technology (flow, alternating polarity) and understanding that fundamentally improve selectivity. Among these is its innovative merger with PRC (synthetic PEC) in a fashion that tackles the issues of both parent techniques and has risen to the forefront of

• efficiency and selectivity of the reactions (vide infra, conPET section). Electrolytes have the potential to be i) aqueous-separated and recovered in batch, or ii) decreased, even ultimately eliminated by flow reactors as an engineering control. Regarding purely the chemical reactivity and scope of

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• purified by preparative HPLC on YMC-Pack-ODS-A with aqueous MeCN (63%), and then purified by semi-preparative HPLC on YMC-Pack-ODS-A with aqueous MeOH (82%) to afford 7 (36.1 mg, tR = 21.3 min; flow rate: 3 mL/min). Fr.6.5 (9.3 g) was further fractionated into ten parts (Fr.6.5.1–Fr.6.5.10) by a silica gel

• min, flow rate: 3 mL/min). Fr.6.5.8 (787.3 mg) was separated by VLC on silica gel eluted with petroleum ether/acetone (25:1–1:1) to provide six portions (Fr.6.5.8.1–Fr.6.5.8.6). Fr.6.5.8.4 (91.0 mg) was further purified by semi-preparative HPLC on SEP Basic 120 C18 with aqueous MeCN (46%) to afford 10

• (4.5 mg, tR = 24.9 min; flow rate: 3 mL/min). Fr.6.6 (9.1 g) was further divided into fifteen parts (Fr.6.6.1–Fr.6.6.15) by a YMC-ODS column (MeOH, 45–80%). Fr.6.6.10 (747.8 g) was separated a by silica gel column washed with petroleum ether/acetone (1:9–6:4) to yield thirteen portions (Fr.6.6.10.1–Fr

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• , Macherey-Nagel) and a gradient of acetonitrile in water supplemented with 0.1% (v/v) trifluoroacetic acid. The gradient conditions were as follows: from 20% acetonitrile to 90% in 30 minutes and kept at 90% for 10 minutes. The flow rate was set to 5 mL/min. The elution of compounds was monitored with a

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• /H2O, 70%). Fr. E25 (248.6 mg) was subjected to preparative HPLC (MeOH/H2O (0.04% TFA), 50–100%, flow rate: 10 mL min−1) to obtain six fractions (Fr. E251–Fr. E256). Fr. E254 was concentrated under reduced pressure to yield compound 9 (20.00 mg). Additionally, Fr. E255 (51.8 mg) was further purified

• using semi-preparative HPLC (C30, MeOH/H2O, 25%, flow rate: 3 mL min−1) to yield compound 8 (16.23 mg, tR = 25.04 min). Fr. E5 (9.0 g) was separated into eleven parts (Fr. E51–Fr. E59, Fr. E5A–B) by Sephadex LH-20 (MeOH/H2O, 70%). Fr. E53 (4.26 g) was divided into eleven portions (Fr. E531–Fr. E539, Fr

• :1–1:1), and Fr. E53732 (63.8 mg) was further purified using semi-preparative HPLC (ODS-A, MeCN/H2O (0.04% TFA), 55%, flow rate: 3 mL min−1) to afford compound 7 (15.70 mg, tR = 14.05 min). Fr. E54 (415.3 mg) was separated into twelve fractions (Fr. E541–Fr.E549, Fr. E54A–Fr.E54C) using an MCI gel

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• 10.3762/bjoc.19.55 Abstract We report on the high potential of a honeycomb reactor for the use in aerobic oxidation under continuous-flow conditions. The honeycomb reactor is made of porous material with narrow channels separated by porous walls allowing for high density accumulation in the reactor. This

• structure raised the mixing efficiency of a gas–liquid reaction system, and it effectively accelerated the aerobic oxidation of benzyl alcohols to benzaldehydes under continuous-flow conditions. This reactor is a promising device for streamlining aerobic oxidation with high process safety because it is a

• from operators or the equipment can have disastrous consequences. Because the large headspace of batch reactor aggravates these safety risks, the use of O2 in batch manufacturing is very limited [14]. Recently, continuous flow synthesis has recently been studied as a way to mitigate the safety risks

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• develop a continuous flow process specifically for the C3-alkylation of furfural (Murai reaction). The transposition of a batch process to a continuous flow process is often costly in terms of time and reagents. Therefore, we chose to proceed in two steps: the reaction conditions were first optimized

• using a laboratory-built pulsed-flow system to save reagents. The optimized conditions in this pulsed-flow mode were then successfully transferred to a continuous flow reactor. In addition, the versatility of this continuous flow device allowed both steps of the reaction to be carried out, namely the

• formation of the imine directing group and the C3-functionalization with some vinylsilanes and norbonene. Keywords: biomass; C–H activation; flow; furfural; homogeneous catalysis; Introduction The conversion of biomass derivatives into value-added products is one of the key branches of green chemistry and

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• . Note that in 2018, Besset and Lebel developed a more efficient process for the palladium-catalyzed trifluoromethylthiolation by C–H bond activation under continuous flow conditions [127]. I.4) Difluoromethylthiolation of aromatic and vinylic C(sp2)–H bonds (C–SCF2H and C–SCF2CO2Et bonds) More recently

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• a Netzsch 204 F1 Phoenix apparatus (both from Netzsch Group, Selb, Germany). The TG–DTG and DSC conditions were similar: temperature program of 25–500 °C, with a heating rate of 10 °C/min, nitrogen purge and protection flow of 40 mL/min, the data acquisition and handling by Netzsch Proteus-Thermal

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• of Science, Charles University, 128 43 Prague 2, Czech Republic 10.3762/bjoc.19.25 Abstract The first continuous flow method was developed for the synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin starting from native β-cyclodextrin through three reaction steps, such as monotosylation, azidation

• and reduction. All reaction steps were studied separately and optimized under continuous flow conditions. After the optimization, the reaction steps were coupled in a semi-continuous flow system, since a solvent exchange had to be performed after the tosylation. However, the azidation and the

• reduction steps were compatible to be coupled in one flow system obtaining 6-monoamino-6-monodeoxy-β-cyclodextrin in a high yield. Our flow method developed is safer and faster than the batch approaches. Keywords: azidation; continuous flow; β-cyclodextrin; H-cube; 6-monoamino-6-monodeoxy-β-cyclodextrin

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• K. HFIP was supplemented with 3 g/L potassium triflate, and the flow rate was adjusted to 0.50 mL/min. Calibration was performed using PEG standards with molar masses ranging from 0.1–1,000 kg/mol. Before every measurement, samples were filtered through 0.2 µm PTFE filters, Roth (Karlsruhe, Germany

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• (0.1% TFA) were held for the first 1 min, followed by a linear gradient to 100% MeOH (0.1% TFA) over 59 min, all at a flow rate of 9 mL/min. Sixty fractions (60 × 1 min) were collected from the start of the HPLC run. Fractions containing UV-active material were analysed by 1H NMR spectroscopy and LCMS

• first 1 min, followed by a linear gradient to 80% MeOH/20% H2O (0.1% TFA) over 59 min, all at a flow rate of 9 mL/min. 3-(4-(Difluoromethoxy)phenyl)-5-phenethoxy-8-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyrazine (10). White amorphous solid (6 mg, 12%); UV (MeOH) λmax (log ε): 243 (3.94), 324 (3.50) nm

Modern flow chemistry – prospect and advantage

• Philipp Heretsch

Beilstein J. Org. Chem. 2023, 19, 33–35, doi:10.3762/bjoc.19.3

• Philipp Heretsch Institute of Organic Chemistry, Leibniz Universität Hannover, Schneiderberg 1B, 30167 Hannover, Germany 10.3762/bjoc.19.3 Keywords: flow chemistry; method development; reactor design; Organic chemistry has shaped modern society by fulfilling the basic needs for pharmaceuticals

• , agrochemicals, fragrances, and many more. Implementation of new and innovative technologies has played a vital role in this mission and has contributed to the opening of new research areas and to pushing the frontiers of existing ones. Among these new technologies, continuous flow chemistry has stepped on the

• chemicals. This has again led to improved scalability, higher purity of products, and eventually decreased manufacturing costs. From the undisputed role of continuous flow chemistry for process chemists, the advent of this technology in academic research laboratories, especially for method development and

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• continuous-flow procedure for the generation of six-membered diaryliodonium salts. The accompanying scalability and atom economy are significant improvements to existing batch methods. Benzyl acetates are submitted to this two-step procedure as highly available and cheap starting materials. An acid-catalyzed

• Friedel–Crafts alkylation followed by an anodic oxidative cyclization yielded a defined set of cyclic iodonium salts in a highly substrate-dependent yield. Keywords: electrochemistry; flow chemistry; hypervalent compounds; iodine; oxidation; Introduction Hypervalent iodine compounds (HVI) are well

• anodic oxidation [37][38][39][40]. Due to the apparent advantages of electrochemical processes, their implementation in flow is simple and straightforward since further dilution or additives are unnecessary [41][42]. One early example of this combination in the field of HVI chemistry is the anodic

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• , bipolamine I (176) was obtained from 169 via a samarium diiodide reduction of the mesylate, followed by sodium borohydride reduction of the ketone, hydroboration, and base-mediated cyclization. Flow-controlled divergent synthesis of aporphine and morphinandienone natural products (Felpin 2022) [92

• reported the flow-controlled divergent synthesis of aporphine and morphinandienone alkaloids based on biomimetic common scaffolds (e.g., 180) using hypervalent iodine(III) reagents. Capitalizing on previously reported mechanistic investigations, they assumed that 180 can rearrange to glaucine (183) through

• produce aporphine natural products, while the use of PIDA or PIFA in the presence of BF3·OEt or TMSOTf in wet CH3CN allows to diverge the synthesis to morphinandienone natural products (e.g., 181, Scheme 15). The flow reaction was performed in a reaction coil at room temperature. Two reaction loops were

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• under dry nitrogen gas with a constant flow rate of 60 cm3·min−1 and the samples were heated to a maximum temperature of 400 °C at a constant rate of 10 K·min−1. Differential scanning calorimetry (DSC): DSC analyses were performed on a DSC XP-10 instrument (Surface Solutions GmbH), and the data analysed

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• Jorge Garcia-Lacuna Marcus Baumann School of Chemistry, University College Dublin, Science Centre South, Belfield, Dublin 4, Dublin, Ireland 10.3762/bjoc.18.182 Abstract Continuous flow technology has become the method of choice for many academic and industrial researchers when developing new

• exploited to achieve effective and reliable flow processes. This perspective article summarizes recent applications of different inline purification techniques such as chromatography, extractions, and crystallization from academic and industrial laboratories. A discussion of the advantages and drawbacks of

• these tools is provided as a guide to aid researchers in selecting the most appropriate approach for future applications. It is hoped that this perspective contributes to new developments in this field in the context of process and cost efficiency, sustainability and industrial uptake of new flow

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• -inflammatory [4][5][6][7][8], insecticidal, fungicidal, etc [9]. In addition to the above-mentioned activities, macarpine was also used as a DNA probe for flow cytometry and fluorescence microscopy due to its fluorescent properties [10]. Despite some research on the activities of macarpine had been performed

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• % formic acid) were employed for the first minute, followed by a linear gradient to 100% MeOH (0.1% formic acid) over 8 min followed by a 1.5 min isocratic elution of 100% MeOH (0.1% formic acid) all at a flow rate of 0.3 mL/min. UHPLC–MS data was analysed using Thermo Scientific Dionex Chromeleon 7

• a further 10 min, all at a flow rate of 9 mL/min. Sixty 1 min fractions were collected from time 0 to 60 min to afford 5-debromopurealidin H (1, 11.1 mg, tR 32–34 min, 0.111% dry wt), and the known alkaloid ianthesine E (2, 161.2 mg, tR 40–41 min, 1.612% dry wt). 5-Debromopurealidin H (1): Yellow

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• note here that the system is kept under a constant flow of either argon or nitrogen, mainly to avoid side reactions with components in the air (humidity, oxygen), but also to prevent the solid in the addition funnel from contacting any vapour and turning soggy before it is added to the round-bottomed

• flask. As can be seen in Figure 1, this is achieved by flowing the gas through the powder addition funnel via a gas inlet. This also allows for the quick removal (usually complete in less than 30 minutes) of residual triisopropyl phosphite at the end of the reaction by simply increasing the gas flow

Molecular and macromolecular electrochemistry: synthesis, mechanism, and redox properties

• Shinsuke Inagi and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 1505–1506, doi:10.3762/bjoc.18.158

• of organic electrochemistry for energy material applications. Organic semiconductor design for electron or hole transport is important for transistor and solar cell applications, and redox-active (but stable) organic and polymeric materials are promising for secondary batteries and redox flow

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• with the measured values. The CT character of the 1CT and 3CT states is visible in the electronic density difference (EDDs) plots shown in Scheme 2, which clearly indicates the flow of electron density from the PTZ to the NI moieties. Conversely, the LE states are fully localized within the acceptor

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• effect on an animal model of the disease. Then, past these two hurdles, the task of selecting a clinical candidate and produce up to tons of it is also a major endeavor that has been often overlooked by the academia. However, a noteworthy exception would be the recent flow chemistry developments in the

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• into new modes to activate matter by force (e.g., twin-screw extrusion [71], resonant acoustic mixing [72], vortex fluidic mixing [73], laminar flow [74], etc.) will continue to unveil similarities and complementarities, rather than disparities, between the ways polymer and small molecule

• mechanochemical reactions occur. As a result, the field of mechanochemistry as a whole will ultimately be strengthened. Representation of (a) cavitation and elongational flow caused by pulsed ultrasonication, (b) mixer mill, (c) planetary ball mill, and (d) ring-and-puck mill (vibrating disc mill). Structure of