Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• OEEFs (Figure 9B). To elaborate on these great expectations, pristine MWCNTs 3 were drop casted on the graphite anodes of electrochemical microfluidic reactors [44]. The substrate was injected by a syringe pump, the product was collected at the other end of the microflow channel and analyzed by HPLC

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

• Nations in 2015. This is evidenced by the recent publication of special issues on organic electrosynthesis in various academic journals [1][2][3][4][5]. In addition to the conventional two- or three-electrode batch-type electrolytic cells, recent developments include microflow electrolytic reactors

Synthesis of piperidine and pyrrolidine derivatives by electroreductive cyclization of imine with terminal dihaloalkanes in a flow microreactor

• Yuki Naito,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 350–359, doi:10.3762/bjoc.18.39

• ]. The key features of this method are the effective cathodic reduction of imines and their rapid use for the subsequent reactions in a microflow system. Successful preliminary results prompted us to perform the electroreductive cyclization of an imine with terminal dihaloalkanes to afford heterocyclic

High-speed C–H chlorination of ethylene carbonate using a new photoflow setup

• Takayoshi Kasakado,
• Takahide Fukuyama,
• Tomohiro Nakagawa,
• Shinji Taguchi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2022, 18, 152–158, doi:10.3762/bjoc.18.16

• is highly desirable in terms of efficiency and safety in handling highly toxic gases such as chlorine. In 2002, Jähnisch and co-workers reported the first microflow chlorination of 2,4-diisocyano-1-methylbenzene, which used a falling-film reactor developed by IMM [9]. While the flow rate employed was

• after the first report on the microflow chlorination of a toluene derivative by Jähnisch and co-workers, we propose a new photoflow setup for C–H chlorination using chlorine gas, applicable to scalable flow C–H chlorination. In our test reaction using C–H chlorination of ethylene carbonate (1

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

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

• and heteroarenes. The use of flow photochemistry allows the reaction to occur 16 times faster than in batch, while at the same time achieving similar yields. Thanks to the intrinsic properties of microflow systems, especially for the scale-up of photochemical processes, we anticipate this procedure

Contribution of microreactor technology and flow chemistry to the development of green and sustainable synthesis

• Flavio Fanelli,
• Giovanna Parisi,
• Leonardo Degennaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2017, 13, 520–542, doi:10.3762/bjoc.13.51

•  1). The use of an integrated microflow system allowed the preparation of functionalized α-ketoamides by a three-component reaction between carbamoyllithium, methyl chloroformate and organolithium compounds bearing sensitive functional groups (i.e., NO2, COOR, epoxide, carbonyl) (Scheme 2). It should

• polyfunctionalized biaryls, using a flow microreactor, has been recently reported by Yoshida [54]. Using the integrated microflow system reported in Scheme 8, arylboronic esters were prepared by a lithiation/borylation sequence, and used in a Suzuki–Miyaura coupling in a monolithic reactor. A remarkable aspect of

• the process was the use of an integrated supported monolithic Pd(0) catalyst that allowed to perform cross-coupling reactions in continuous flow mode (Scheme 8). This integrated microflow system allow to handle the borylation of aryl halides (Ar1X), and the subsequent Suzuki–Miyaura coupling using

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• gaseous and liquid components. The high energy efficiency, low hazard potential, and precise control of reaction parameters have also prompted several adoptions of microflow techniques in technical manufactures of fine chemicals, polymers [26], and pharmaceutical intermediates [27][28][29][30]. The vast

• majority of applications of microflow setups involved reagents in the same aggregation state (homogeneous, mostly liquid phase). In contrast, an especially complex problem beyond the scope of most microreactor setups are heterogeneous reactions [31][32] between three dispersed entities such as a liquid

• gas in the liquid phase which is pressure-dependent according to Henry’s law [69]. Reaction parameters of a model photooxygenation The often poor selectivities of reactions with molecular oxygen (being a triplet biradical in its ground state) [70] have prompted applications of microflow reactors to

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• been adapted to efficiently generate novel small molecules in an electrochemical microflow system [26][30]. Combining the advantages of the cation-pool method with microflow technologies has enabled the concept of “cation flow” systems (Figure 1). In this arrangement a porous carbon felt is used as an

• between anodically generated carbocations occurs by mass transfer diffusion across the liquid–liquid contact area. Therefore, one liquid can be oxidized and the other liquid containing the nucleophile can intercept the N-acyliminium ion formed in the microflow reactor (when the two sides of the channel

• are anode and cathode) (viz. Figure 2). This technique of microflow mixing can also be applied to the synthesis of polymers [29]. A single channel miniaturised microfluidic electrolysis cell that is modular with other microfluidic techniques has now been developed to perform anodic methoxylation

A combined continuous microflow photochemistry and asymmetric organocatalysis approach for the enantioselective synthesis of tetrahydroquinolines

• Erli Sugiono and
• Magnus Rueping

Beilstein J. Org. Chem. 2013, 9, 2457–2462, doi:10.3762/bjoc.9.284

• have been adopted for photochemical applications and microflow photochemistry has emerged as efficient synthesis tool [23][24][25][26][27][28][29][30][31]. The narrow inner dimensions of microfabricated reactors is advantageous for photochemical synthesis since it allows better light penetration and

• isolated in 59% yield and 93% enantiomeric excess (Table 1, entry 1 vs entry 2). Improvement of the reaction yield shows the superior performance of the microflow reactor since the light penetration through the microchannels was significantly increased. A slight improvement of yield was achieved when the

Microflow photochemistry: UVC-induced [2 + 2]-photoadditions to furanone in a microcapillary reactor

• Sylvestre Bachollet,
• Kimitada Terao,
• Shin Aida,
• Yasuhiro Nishiyama,
• Kiyomi Kakiuchi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2013, 9, 2015–2021, doi:10.3762/bjoc.9.237

• chemistry; furanone; microflow chemistry; photochemistry; Introduction Continuous-flow chemistry has recently emerged as a new methodology in organic chemistry [1][2][3][4]. The combination of microstructured dimensions and flow operations has also proven advantageous for photochemical applications [5][6

• . However, higher cycloalkenes (cyclohexene and cis-cyclooctene) gave stereoisomeric mixtures even under these direct irradiation conditions. Microflow photochemical syntheses with UVC light are rare. Jamison and coworkers have recently used custom-made quartz coils [32][33], however, these are difficult to

• smaller diameter, the light transmission in the microcapillary was still superior with 53%, compared to 0.3% in the test tube. [2 + 2]-Cycloadditions with cyclopentene The photoaddition of cyclopentene (2) to 1 was subsequently investigated in detail under batch and microflow conditions (Scheme 2, Table 1

Flow Giese reaction using cyanoborohydride as a radical mediator

• Takahide Fukuyama,
• Takuji Kawamoto,
• Mikako Kobayashi and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2013, 9, 1791–1796, doi:10.3762/bjoc.9.208

• flow reaction technology [31]. In this study, we report that cyanoborohydride-based Giese reactions of primary, secondary, and tertiary iodoalkanes with ethyl acrylate can be carried out efficiently using a microflow system. Optimal conditions for each substrate were quickly determined by the use of an

• automated microflow reactor [32], which revealed that running the continuous flow reactions at 70 °C for 10–15 min gave good yields of Giese addition products with effective suppression of the byproducts. Results and Discussion We employed an automated microflow reactor system, MiChS® System X-1 [33

• cyanoborohydride-mediated Giese reaction of alkyl iodides 1a, 1b, and 1c with ethyl acrylate was studied in a continuous microflow reaction system. Optimized conditions with minimum formation of byproducts for the conversion of 1a to 3a were rapidly located by the use of an automated microflow system, MiChS® X-1

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

• -reactor system that have been used for synthetic photochemistry. • Microflow [19]. These devices consist of fabricated microchannels and range from bespoke “lab-on-a-chip” designs to highly engineered glass and metal systems. They are generally defined as having channels less than 1 mm in thickness and

• theoretical productivity of the reaction if all the emitted photons are absorbed. The small aperture and limited channel coverage of a microflow reactor puts it at a distinct disadvantage in this aspect. The microchannels are milled or etched into a planar surface and cannot efficiently capture the radial

• emission from most common light sources. Even LEDs, which can be considered as planar light sources, often have a beam width wider than the actual channels; however, this issue could easily be addressed by a more directed reactor design. As a result microflow reactors are often inefficient at capturing

Continuous-flow catalytic asymmetric hydrogenations: Reaction optimization using FTIR inline analysis

• Magnus Rueping,
• Teerawut Bootwicha and
• Erli Sugiono

Beilstein J. Org. Chem. 2012, 8, 300–307, doi:10.3762/bjoc.8.32

• . The internal reaction temperature was monitored with an internal thermal sensor. The ReactIR 45m microflow cell equipped with a DiComp ATR (diamond-composite attenuated total reflection) probe was attached to the microreactor at the end of the reaction stream and was used as an inline analytical tool

Koch–Haaf reaction of adamantanols in an acid-tolerant hastelloy-made microreactor

• Takahide Fukuyama,
• Yu Mukai and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2011, 7, 1288–1293, doi:10.3762/bjoc.7.149

• Takahide Fukuyama Yu Mukai Ilhyong Ryu Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan 10.3762/bjoc.7.149 Abstract The Koch–Haaf reaction of adamantanols was successfully carried out in a microflow system at room temperature. By

• organic molecules, and we also reported that Pd-catalyzed carbonylation [13] and radical carbonylation [16] could be successfully carried out in a continuous microflow system with higher efficiency than in a batch autoclave system. In this study, we focused on the carbonylation of carbocation

• intermediates carried out in a continuous microflow system [22][23][24]. The Koch–Haaf reaction [25], that is the carbonylation of alcohols or olefins with formic acid in the presence of a strong acid, is an important reaction for the preparation of carboxylic acids, which are widely used in organic synthesis

Scaling up of continuous-flow, microwave-assisted, organic reactions by varying the size of Pd-functionalized catalytic monoliths

• Ping He,
• Stephen J. Haswell,
• Paul D. I. Fletcher,
• Stephen M. Kelly and
• Andrew Mansfield

Beilstein J. Org. Chem. 2011, 7, 1150–1157, doi:10.3762/bjoc.7.133

• demonstrated by Uozumi et al. [11], where carbon–carbon bond forming reactions of aryl halides and arylboronic acids under microflow conditions can be achieved quantitatively within 4 s residence time. However, the stability of the catalytic membrane was not discussed. Monolith based devices have shown good

A practical microreactor for electrochemistry in flow

• Kevin Watts,
• William Gattrell and
• Thomas Wirth

Beilstein J. Org. Chem. 2011, 7, 1108–1114, doi:10.3762/bjoc.7.127

• -supported, paired electrosynthesis of 2,5-dimethoxy-2,5-dihydrofuran from furan with excellent yields and flow rates of up to 0.5 mL·min−1. A microflow system where the current flow and liquid flow are parallel was reported by Yoshida et al. [7]. Two carbon fibre electrodes were separated by a hydrophobic

• the continuous synthesis of diaryliodonium compounds. A microflow electrochemical reactor made out of two aluminium bodies (50 mm diameter, 25 mm height) was manufactured. The electrodes are constructed of two PTFE plates (35 mm diameter, 4 mm height) onto which 0.1 mm platinum foil electrodes [16

Microphotochemistry: 4,4'-Dimethoxybenzophenone mediated photodecarboxylation reactions involving phthalimides

• Oksana Shvydkiv,
• Kieran Nolan and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2011, 7, 1055–1063, doi:10.3762/bjoc.7.121

• intra- and intermolecular photodecarboxylation reactions involving phthalimides have been examined under microflow conditions. Conversion rates, isolated yields and chemoselectivities were compared to analogous reactions in a batch photoreactor. In all cases investigated, the microreactions gave

• superior results thus proving the superiority of microphotochemistry over conventional technologies. Keywords: microflow; microreactor; photochemistry; photodecarboxylation; phthalimide; Introduction Organic photochemistry is a highly successful synthesis method that allows the construction of complex

• considered “exotic” by synthetic chemists [12]. Over the last decade, microflow chemistry has emerged as a new tool in preparative organic chemistry [13][14][15][16]. Microflow reactors (μ-reactors) offer a number of advantages for photochemical transformations. In particular, their narrow reaction channels

Acid- mediated reactions under microfluidic conditions: A new strategy for practical synthesis of biofunctional natural products

• Katsunori Tanaka and
• Koichi Fukase

Beilstein J. Org. Chem. 2009, 5, No. 40, doi:10.3762/bjoc.5.40

• 13 and 14 in excellent yields, respectively (entries 3 and 4). The BH3·Et3N in MeCN system was also applicable to the microflow reduction of muramic acid derivative 9, which contains a lactic acid ester at the C3-hydroxyl, affording 6-O-benzyl derivative 15 as a single isomer (entry 5). Finally, the

• performed in each entry of Table 3. Furthermore, no special dehydration procedures, such as pre-drying of the reaction apparatus and the solvents by molecular seives, are necessary, making the present microflow reaction a practical procedure for large-scale synthesis [30]. Based on the established

Radical carbonylations using a continuous microflow system

• Takahide Fukuyama,
• Md. Taifur Rahman,
• Naoya Kamata and
• Ilhyong Ryu

Beilstein J. Org. Chem. 2009, 5, No. 34, doi:10.3762/bjoc.5.34

• Takahide Fukuyama Md. Taifur Rahman Naoya Kamata Ilhyong Ryu Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan 10.3762/bjoc.5.34 Abstract Radical-based carbonylation reactions of alkyl halides were conducted in a microflow reactor under

• demonstrated by our group [4][5][6] as well as others [7][8][9][10][11]. In our recent report, we demonstrated that excellent thermal efficiency of the microflow system would lead to effective execution of tin hydride and TTMSS (tris(trimethylsilyl)silane)-mediated radical reduction and cyclization reactions

• [12]. The Seeberger group reported reduction and hydrosilylation using TTMSS in a microflow system [13]. In our study, we found that the combination of a rapidly decomposing radical initiator with a microreaction device allowed the reactions to be completed in a very short period of time giving good

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• significantly higher when compared to a carousel-type reactor typically used for parallel synthesis. Organocatalytic asymmetric aldol reactions in microflow devices were recently reported by our laboratory [15]. The aldol condensation of various aromatic aldehydes with acetone was carried out at higher

Oxidative cyclization of alkenols with Oxone using a miniflow reactor

• Yoichi M. A. Yamada,
• Kaoru Torii and
• Yasuhiro Uozumi

Beilstein J. Org. Chem. 2009, 5, No. 18, doi:10.3762/bjoc.5.18

• molecular diffusion path in narrow space reactors often drastically improve the efficiency of a given chemical reaction. As a case in point, we have previously developed a catalyst-installed microflow reactor where a membranous polymeric palladium catalyst was deposited inside a micro-channel reactor at the

• laminar flow interface [16], resulting in the instantaneous production of biaryls (quantitative yield within 4 s of residence time) via a palladium-catalyzed Suzuki-Miyaura reaction under microflow conditions. An additional advantage of micro- and minireactors is the small heat capacity of the micro- and

Synthesis of unsymmetrically substituted biaryls via sequential lithiation of dibromobiaryls using integrated microflow systems

• Aiichiro Nagaki,
• Naofumi Takabayashi,
• Yutaka Tomida and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2009, 5, No. 16, doi:10.3762/bjoc.5.16

• Aiichiro Nagaki Naofumi Takabayashi Yutaka Tomida Jun-ichi Yoshida Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyotodaigakukatsura, Nishikyo-ku, Kyoto, 615-8510, Japan 10.3762/bjoc.5.16 Abstract A microflow system consisting of

• with 1 equiv of n-butyllithium followed by the reaction with electrophiles was achieved using a microflow system by virtue of fast micromixing and precise temperature control. Sequential introduction of two different electrophiles was achieved using an integrated microflow system composed of four

• micromixers and four microtube reactors to obtain unsymmetrically substituted biaryl compounds. Keywords: dibromobiaryls; fast mixing; integrated microflow system; selective lithiation; unsymmetrically substituted biaryls; Introduction Unsymmetrical biaryls have received significant research interest