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

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• ]. Noël and co-workers reported the C3–H olefination of indoles using Pd(OAc)2 as a catalyst and molecular oxygen as the oxidant under continuous flow conditions [29]. Jia et al. reported the synthesis of 3-alkenylindoles using Pd(OAc)2 as the catalyst and MnO2 as the oxidant under ball milling conditions

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• heterogeneous and homogeneous catalysts, as well as continuous-flow conditions [13][14][15]. Therefore, we tested microwave heating, a technique which is known for significant acceleration of the C–C coupling reaction [16]. We carried out the optimization studies using model substrates – compound 1a and benzyl

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• mostly chemically indistinguishable, while many P450s are known to selectively act on specific carbon atom(s). A continuous electron input is required to keep CYPs functional [83]. In general, soluble bacterial CYPs utilize class I redox systems, where the electron from NAD(P)H is delivered to CYPs

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• continuous darkness. Headspace collection and GC–MS analysis On the 8th day and 18th day after the transfer of plasmodia to a fresh agar plate, volatiles were collected from the headspace of plasmodia on the agar plate using solid phase microextraction (SPME) (https://www.sigmaaldrich.com). After collection

Dyes in modern organic chemistry

• Heiko Ihmels

Beilstein J. Org. Chem. 2019, 15, 2798–2800, doi:10.3762/bjoc.15.272

• examples clearly show that dye chemistry is a mature and essential topic in organic chemistry, it still constitutes a vibrant research area because of the continuous need for specifically designed dyes with custom-made optical properties for diverse topical applications. Hence, this special issue aimed at

• continuous support. Heiko Ihmels Siegen, October 2019

Progress in metathesis chemistry

• Karol Grela and
• Anna Kajetanowicz

Beilstein J. Org. Chem. 2019, 15, 2765–2766, doi:10.3762/bjoc.15.267

• pills are now truly user friendly. Olefin metathesis catalysts can work under homo- or heterogeneous conditions, as well as under continuous flow. The stability of Ru–methylidene species (an attribute important for a successful ethenolysis process) has been significantly improved. Importantly, we have

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• reflections (Rint 0.0375), R1 0.0439, wR2 0.1215, S 1.011 [for 3451 I > 2σ(I)]. EPR measurements Continuous wave (CW) EPR measurements were carried out using a commercial Bruker Elexsys E540 X-band spectrometer. The CW EPR spectra were simulated using EasySpin [18]. Pulse EPR experiments were carried out

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• explosive azide chemistry involved in a proposed Tamiflu route by taking advantage of the continuous-flow technology. The azide intermediates were safely synthesised in full conversions and >89% isolated yields. Keywords: azide chemistry; continuous flow synthesis; hazardous; safe; Tamiflu; Introduction

• ) (Scheme 1 and Figure 1). Continuous-flow synthesis offers the generation and consumption of dangerous intermediates in situ preventing their accumulation, thus it represents a potential solution for dealing with hazardous reaction intermediates and products [15]. Additionally, microreactors can handle

• exothermic reactions extremely well, due to the inherent high surface area to volume ratio and rapid heat dissipation [16] unlike the conventional batch process. Continuous-flow production may certainly enhance the green metrics of synthesis in several ways [17] and their work clearly demonstrated the

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• -acetylation using NaOMe in MeOH followed by hydrogenolysis in a ThalesNano continuous flow hydrogenation assembly using a 10% Pd-C cartridge [29]. After three cycles of hydrogenation, formation of the target pentasaccharide 1 was evident from the mass spectrum (Scheme 4). Conclusion In conclusion, the

In search of visible-light photoresponsive peptide nucleic acids (PNAs) for reversible control of DNA hybridization

• Lei Zhang,
• Greta Linden and
• Olalla Vázquez

Beilstein J. Org. Chem. 2019, 15, 2500–2508, doi:10.3762/bjoc.15.243

• irradiated to obtain maximal cis (oF4Azo, 520 nm, 10 min) or trans (HTI, 405 nm, 2 min) and stored in the dark. PNA12(oF4Azo) (3) was also measured with continuous heating at 90 °C (gray squares). UV–vis spectra were collected at different time points during 10 h. Curves derived were calculate from two

Reversible switching of arylazopyrazole within a metal–organic cage

• Anton I. Hanopolskyi,
• Soumen De,
• Michał J. Białek,
• Yael Diskin-Posner,
• Liat Avram,
• Moran Feller and
• Rafal Klajn

Beilstein J. Org. Chem. 2019, 15, 2398–2407, doi:10.3762/bjoc.15.232

• this notion, we prepared pure Z-1 (by evaporating the solvent from a solution of E-1 in acetonitrile under continuous UV irradiation) and i) confirmed its high solubility in water (see Figure S24 in Supporting Information File 1 for an NMR spectrum of Z-1 in D2O) and ii) demonstrated light-controlled

Excited state dynamics for visible-light sensitization of a photochromic benzil-subsituted phenoxyl-imidazolyl radical complex

• Yoichi Kobayashi,
• Yukie Mamiya,
• Katsuya Mutoh,
• Hikaru Sotome,
• Masafumi Koga,
• Hiroshi Miyasaka and
• Jiro Abe

Beilstein J. Org. Chem. 2019, 15, 2369–2379, doi:10.3762/bjoc.15.229

• fs is the apparent lifetime because the conformational change from the skewed to the planar structure at sub-picosecond time scale induces the continuous spectral shift. Because the present SVD global analyses do not consider the continuous spectral shift, it is difficult to extract the exact time

• ≈2 ps [45]. The similarity of the time constant of the bond breaking to that of EAS1 supports that the C–N bond is cleaved by the direct excitation of the PIC unit. The spectral evolution from EAS2 (1.4 ps) to EAS3 (38 ps, green in Figure 3d) shows the continuous spectral shift due to the benzil unit

• and the increase in the absorption due to the biradical form (660 nm). Because the continuous spectral shift due to the benzil unit is still observed in EAS2 (1.4 ps), it is suggested that the structural change of the benzil unit of Benzil-PIC is somehow slightly decelerated as compared to that of

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• Ministry of Economic Affairs, Regional Development and Energy for the bioinsecticide project (Grant #1340/68351/13/2013). We are grateful to M. Wahl for continuous encouragement and support.

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• , agricultural, and materials industries. The incorporation of fluorine-containing groups into organic molecules can improve their chemical and physical properties, which attracts continuous interest in organic synthesis. Among various reported methods, transition-metal-catalyzed fluorination/fluoroalkylation

• dehydrogenation process to afford the target product. Also in 2015, Li and co-workers [146] developed a mild and fast Cu(I/II)-catalyzed trifluoromethylation procedure to obtain 3-trifluoromethylcoumarins. The reaction was carried out with a CuCl/CF3SO2Na/TBHP system under continuous-flow conditions, affording