N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• was the only effective reagent when performing the reaction at 60 °C in THF [16]. Ketimines were also synthesized with Ti(OEt)4, under microwave irradiation in a solvent-free system [20]. In hindered ketones, Ti(OiPr)4 or Ti(OEt)4 using vacuum or under a nitrogen flow were effective to tert

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• , continuous-flow reactions are currently a general challenge, especially for the pharmaceutical industry. The prerequisite for a successful continuous synthesis in the field of asymmetric addition reactions to enones is the mastery of recyclable heterogeneous catalysis. Very recently, we reported [57] the

• first heterogeneous polystyrene-supported recyclable catalyst for asymmetric conjugate addition reactions of arylboronic acids to five and six-membered enones. In our laboratory, we also attempted to perform this reaction under flow conditions. However, the change from batch to flow arrangement itself

• is another challenging task. Nevertheless, it should be noted at this point that in the case of rhodium complex catalysis, the asymmetric addition of phenylboronic acid to enones in continuous flow has been successful [24]. In 2021, Walhers et al. presented a theoretical study based on the Q2MM

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• 5a–e in the presence of ct DNA were examined with flow linear dichroism (LD) and circular dichroism (CD) spectroscopy (Figure 5, Figure S6, Supporting Information File 1). The binding of ligands 5a–e resulted in the development of negative LD signals at 350–355 nm and 420–429 nm clearly indicating an

• dichroism (LD): Chirascan CD spectrometer, Applied Photophysics. Flow-LD: High Shear Cuvette Cell Accessory (Applied Photophysics); the LD samples were recorded in a rotating cuvette with a shear gradient of 1200 s−1. Melting points: Büchi 545 (Büchi, Flawil, CH). Materials Berberrubine (1b) was synthesized

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• was reduced under nitrogen flow. The received solid product was dissolved in DCM and subsequently reduced under nitrogen flow. This procedure was repeated two more times, followed by a lyophilization step to receive the crude peptide. The crude T7–lipid conjugate was purified by normal-phase

• was used to detect the LNPs, with a slide shutter level set to 1232 and the slider gain set to 219, and the syringe pump speed set to 30 using a flow-cell top plate module. Cell lines and maintenance HeLa and HEK293T cells were purchased from American Type Culture Collection (ATCC, VA). TZM-bls were

• h later, the apical layer was removed, and the basolateral cells were washed, trypsinized, and resuspended in 1× PBS. Detection of Cy5 was measured by flow cytometry on a BD Accuri™ C6 device (Becton, Dickinson and Company, NJ), and the data was analyzed using FlowJo™ Version 10.7.1 (Becton

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• seems to be compromised imposing restrictions on using microwaves at a scale-up level. However, the batch process and continuous flow process seem to provide an entry into scale-up standards with safety. The microwave reactors serving the purpose of batch and parallel approach are designed in various

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• the secondary amine catalyst (Scheme 39). In 2019, Kappe and colleagues [36] reported a method to complete perfluoroalkylation of olefins under visible light in flow. Perfluoroalkylated olefin 118 was prepared by employing olefin 116 and perfluoroalkyl iodides 117 as substrates as well as

• triethylamine as additive at 20 °C and under 405 nm irradiation (Scheme 40). A standard residence time of 5 min was required for the full conversion via the EDA complex that formed by alkene and perfluoroalkyl iodide in flow, while longer residence times were requisite for less reactive alkenes. Moreover, the

• yield of this reaction can reach 7.6 g ⋅ h−1 on a gram scale, indicating that the flow step is promising in photochemistry. In 2019, Aggarwal and colleagues [38] employed Katritzky salt 119 as electron acceptor and HE 79 as electron donor to form an EDA complex, providing the corresponding alkyl radical

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• cholesterol 44 and histamine 45. Scientific literature [97] reports a three-step continuous synthesis of [6,6]-tert-butyl phenyl-C61-butyrate 47 based on tert-butyl 4-benzoylbutyrate hydrazone in a microstructured flow reactor that eliminates the need for stage-by-stage isolation of intermediate products and

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

• acetonitrile 20:80 (v/v) at a flow rate of 0.5 mL/min. (SG)5-KSS-K(C2H4-C6F13)2 (1) was synthesized according to the general procedure using 4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluorononanoic acid. Yield: 121 mg (6.3%); FABMS (m/z): 1916 [M + H]+; HRMS (m/z): [M + H]+ calcd for C61H84F26N17O23, 1916.5511; found

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• equivalents of KHMDS. Further application of this “batch protocol” for a “continuous-flow microreactor” reaction is now ongoing in our laboratory towards industrial collaboration. Experimental A test tube containing 1 (0.4 mmol) in triglyme (0.7 mL) was charged with HCF3 (9.9 mL, 1.1 equiv, measured by a

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• pressure: 77.1 kPa, He flow: 23.3 mL min−1, 2) injection volume: 2 μL, 3) splitless injection, 4) temperature program: 5 min isothermic at 50 °C, then increasing with 5 °C min−1 to 320 °C, and 5) He carrier gas flow: 1.2 mL min−1. The parameters of the MS were 1) transfer line temperature: 250 °C, 2) ion

• 2.1L (deuterium lamp, 190–700 nm) and a YMC ChiralART Cellulose-SC column (5 μm; 250 × 20 mm) with a guard column of the same type (30 × 20 mm). The elution was performed with hexane/propanol 60:40 (isocratic) at a flow rate of 10 mL min−1 (36 bar). The UV–vis absorption was monitored at 275 nm

1,2,3-Triazoles as leaving groups: S_NAr reactions of 2,6-bistriazolylpurines with O- and C-nucleophiles

• Dace Cīrule,
• Irina Novosjolova,
• Ērika Bizdēna and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 410–419, doi:10.3762/bjoc.17.37

• Agilent Technologies 1200 Series chromatograph equipped with an Agilent XDB-C18 (4.6 × 50 mm, 1.8 µm) column was used. Eluent A: 0.1% TFA solution with 5% v/v MeCN added; eluent B – MeCN. Gradient: 10–95% B 5 min, 95% B 5 min, 95–10% B 2 min. Flow: 1 mL/min. Wavelength of detection was 260 nm. LC–MS was

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• flow process is presented that couples a Curtius rearrangement step with a biocatalytic impurity tagging strategy to produce a series of valuable Cbz-carbamate products. Immobilized CALB was exploited as a robust hydrolase to transform residual benzyl alcohol into easily separable benzyl butyrate. The

• resulting telescoped flow process was effectively applied across a series of acid substrates rendering the desired carbamate structures in high yield and purity. The derivatization of these products via complementary flow-based Michael addition reactions furthermore demonstrated the creation of β-amino acid

• species. This strategy thus highlights the applicability of this work towards the creation of important chemical building blocks for the pharmaceutical and speciality chemical industries. Keywords: biocatalysis; CALB; Curtius rearrangement; flow synthesis; reaction telescoping; Introduction Continuous

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• this reagent are its safety, low cost, and commercial availability. The reagent is compatible with a range of functionalized substrates for the gem-difluorocyclopropanation when using NaI as an initiator (Table 2). Both, electron-rich and comparatively electron-poor examples have been described. Flow

• reaction conditions were also applied to this reaction (Scheme 15). The reagents were premixed in THF at room temperature and injected into a heated reactor fitted with a back pressure regulator to allow operation at temperatures that exceeded the boiling point of the solvent. In this flow chemistry setup

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• Michael Andresini Leonardo Degannaro Renzo Luisi Flow Chemistry and Microreactor Technology FLAME-Lab, Department of Pharmacy – Drug Sciences, University of Bari “A. Moro”, Via E. Orabona 4, Bari, 70125, Italy 10.3762/bjoc.17.20 Abstract The reported flow-batch approach enables the easy

• and potentially automatable method for the synthesis of interesting strained compounds. Keywords: aziridines; 2H-azirines; flow chemistry; green chemistry; organolithium compounds; Introduction Since their conception in the early 1990s, Green Chemistry Principles (GCP) have been applied with

• risks [6]. Recently, a variety of sustainable solvents has been therefore identified, and their use have been combined with those of enabling technologies. In this scenario, the development of continuous flow synthetic methodologies has found its fortune in the past two decades [7][8][9]. Several

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• an Agilent Technologies 1200 Series system equipped with an XBridge C18 column, 4.6 × 150 mm, particle size 3.5 μm, with a flow rate of 1 mL/min, using eluent A–0.1% TFA/H2O with 5 vol % MeCN and eluent B–MeCN as the mobile phase. The wavelength of detection was 260 nm. Gradient: 30–95% B 5 min, 95

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• authenticated by isothermal calorimetric titration or fluorescence titration and stopped-flow analysis. Furthermore, the quantum yield and reaction velocity of the photocatalysis can be verified by actinometry and UV–vis measurements. Therefore, with the aid of various analytical and spectroscopic studies, we

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• flow rate of 2 mL/min. Low pressure liquid chromatography (LPLC) was performed with a LiChroprep Lobar-A Si 60 column (Merck, Darmstadt, Germany) and an FMI QSY-0 pump. Open columns packed with silica gel 60 (70–230 and 230–400 mesh; Merck), RP-18 silica gel (230–400 mesh; Merck, Darmstadt, Germany

Controlled decomposition of SF₆ by electrochemical reduction

• Sébastien Bouvet,
• Bruce Pégot,
• Stéphane Sengmany,
• Erwan Le Gall,
• Eric Léonel,
• Anne-Marie Goncalves and
• Emmanuel Magnier

Beilstein J. Org. Chem. 2020, 16, 2948–2953, doi:10.3762/bjoc.16.244

• from the consumption of SF6 at the interface electrode/acetonitrile. The current intensity depends on the SF6 flow in agreement with the 1st Fick’s Law from which the Cottrell equation is originated [29]. The upper limit on time was determined from the straight line reported in the insert figure

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• a cryogenically-cooled CCD sensor (Princeton Instruments, PyLoN:2KBUV). To avoid the possible interference by sample container material and to eliminate sample degradation by excess exposure to UV light, the liquid sample was circulated in a home-built free-flow system similar to the one employed

Incorporation of a metal-mediated base pair into an ATP aptamer – using silver(I) ions to modulate aptamer function

• Marius H. Heddinga and
• Jens Müller

Beilstein J. Org. Chem. 2020, 16, 2870–2879, doi:10.3762/bjoc.16.236

• eluents at a flow rate of 1 mL/min: trimethylamine/acetic acid 1:1, 10 mM in water (solvent A) and trimethylamine/acetic acid 1:1, 10 mM in water/CH3CN 1:4 (solvent B). Gradient applied: 0–5 min, 3% B; 5–45 min, 3–40% B; 45–50 min, 100% B. The quantification of the sequences was achieved using a Thermo

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• color patterns (see Supporting Information File 1, Figure S1) [4], are widely distributed, and parapatric in north-eastern Peru [5]. Despite the geographic overlap in distribution, a recent genetic study showed limited gene flow [4]. Reproductive isolation in mimetic butterflies can be driven by

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• flow photoreactors. In this work, we are reviewing structured photoreactors by elaborating on the bottleneck of this field: the development of an efficient scale-up strategy. In line with this, micro- and mesostructured bench-scale photoreactors were evaluated based on a new benchmark called

• designing multiphase photoreactors, and this complicates the design even further [10]. Photoreactions are typically performed in batch reactors. With the process intensification efforts towards green chemistry approaches, continuous flow technologies, micro- and mesostructured flow photoreactors having

• photoreactors with the help of various catalyst structures, beads, static mixers, and/or Taylor flow [4][11]. In addition, these reactors allow safer operation since it is easier to control overheating and the handling of hazardous chemicals in smaller volumes [4][11]. In addition to photomicroreactors, micro

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• ][26][27][28][29]. Therefore, the area of buckybowls particularly sumanene chemistry is gaining more and more pace which can be seen by the inspection of a flow of publications appearing in the literature day-by-day [26]. As far as our knowledge is concerned, this is the first comprehensive review

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• to the 83% yield under the standard conditions. This reaction was also demonstrated in continuous flow under similar conditions [139]. 3.2 Polarity matching-guided unactivated C(sp3)–H fluorination 3.2.1 Synthetic applications: In another seminal paper, Tan and co-workers [198] discovered the

• path length of l = 17.7 mm at which distance (from the surface) 90% of the light is absorbed. Flow chemistry provides an elegant means for scaling photochemical reactions [211][212][213][214], primarily due to the shorter path lengths for light transmission provided by flowing the reaction mixture

• through small-diameter (μm–mm) channels. Lectka and co-workers reported the processing of their benzil-photosensitized enone-directed C(sp3)–H fluorination in a custom-built flow reactor, comprised of a syringe pump, a coil of fluorinated ethylene propylene (FEP) tubing (7.5 m; inner diameter 1.6 mm