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

• . Furthermore, piperidine and pyrrolidine derivatives could be obtained on preparative scale by continuous electrolysis for approximately 1 hour. Keywords: electrochemical synthesis; electrocyclization; flow microreactor; heterocyclic amines; imine; Introduction Heterocycles are a very important class of

• -current electrolysis in a flow microreactor with fixed channel dimensions, the electricity can be controlled by changing the current density or flow rate. As shown in entries 1 and 2 of Table 4, the yield of 3a increased with the electricity (caused by an increase in the current density) and reached a

• electrolyte, the electrolysis reaction could not be carried out because Et4N∙ClO4 did not dissolve in the THF solution. On the other hand, n-Hex4N∙ClO4 dissolved easily in THF solution and the electrolysis reaction proceeded smoothly. However, the yield of the desired product 3a was slightly lower than that

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

• , sustaining the radical chain. Chlorine gas is a cheap feedstock since it is formed as a byproduct of the electrolysis of NaCl to produce NaOH in an industrial process [7]. We felt that C–H chlorination would be updated by using scalable flash chemistry [8]. Flow C–H chlorination using a compact flow reactor

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• scale-up. Proposed mechanism. Optimization of reaction conditions.a Supporting Information Supporting Information File 372: General procedure, characterization data for electrolysis products and NMR spectra. Funding Financial support of this research from NSFC (21971213) and the Fundamental Research

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

• stimulation by application of variable temperature zones, light or microwave irradiation, electrolysis and even high frequency sonication. The ability to quickly and easily assemble and modify a flow setup allows not only the chemical reaction to be performed as a continuous dynamic flow process but also for

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

• per molecule: This preliminary study is an important step to determine the best conditions for the SF6 electrolysis (the choice of potential polarization, the understanding of current decrease). With these analytical data in hands, the large scale decomposition of SF6 was then undertaken. The

• reactions were carried out in a single compartment with a conventional three-electrode arrangement: two platinum electrodes and one silver reference electrode, SRE (Figure 3). The electrolysis is performed at constant potential (−2.3 V vs Fc+/Fc) with a continuous supply of SF6 placed in a rubber balloon

• (constant bubbling). The electrolysis was investigated on the same electrolyte but with larger surface of Pt electrode (15 cm2) (Figure 4). Figure 4b clearly highlights the consumption of the gas by the decrease of the electrochemical waves. The control of the decomposition of the sulfur hexafluoride was

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

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• ) radicals. Since the dawn of organic chemistry, several radical decarboxylations have been developed, including the Kolbe electrolysis [33][34], the Hunsdiecker reaction [35], and the Barton decarboxylation [36][37][38]. More recently, photoredox catalysis has appeared as a mild alternative to these

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• cathode in an undivided cell in the presence of cinchonidine alkaloid as the source of chirality [30]. They modified the electrolysis conditions using a mixture of CH3CN/H2O and tetraethylammonium iodide as the supporting electrolyte and achieved a slight improvement in the enantiomeric excess (Scheme 7

• for the electrocatalytic oxidative coupling of 42 using constant potential electrolysis of the substrates on a graphite felt electrode modified with TEMPO in the presence of (−)-sparteine 43. The electrolysis resulted in (S)-binaphthyl type dimers 44 with excellent yield and enantiomeric excess

• electrolysis strategy allowed the electroreduction of acetophenone (22a) to pinacol (23) with 6.4% ee (Scheme 21). As mentioned by the author, the radical intermediate diffuses from the double layer, and dimerization occurs in the chiral solvent sphere in the solution phase. Chiral supporting electrolyte

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• ] for 1a (Scheme 1). Electrochemically, they report observing a single, two-electron reduction peak and two distinct one-electron oxidation peaks upon scanning using cyclic voltammetry. They therefore proposed [10] that the electrolysis of 1a proceeds by an “ECE” (electrochemical-chemical

• computations predicted a minimal difference. The electrogeneration of 2b through repeated potential step bulk electrolysis of 1b in acetonitrile-d3 yielded a sufficient quantity of LW to obtain a 1H NMR spectrum, which revealed identical chemical shifts as those for the photogenerated 2b. First and second

• 2b. The addition of benzoquinone (a chemical oxidant) to the electrochemically reduced solution under argon gave similar results, consistent with our hypothesis. When the yellow solution remained open to the atmosphere during electrolysis, the initially yellow solution turned green at first

Small anion-assisted electrochemical potential splitting in a new series of bistriarylamine derivatives: organic mixed valency across a urea bridge and zwitterionization

• Keishiro Tahara,
• Tetsufumi Nakakita,
• Alyona A. Starikova,
• Takashi Ikeda,
• Masaaki Abe and
• Jun-ichi Kikuchi

Beilstein J. Org. Chem. 2019, 15, 2277–2286, doi:10.3762/bjoc.15.220

• solvents. To quantify the electronic interactions between the NAr3 units in the MV state, 1b was investigated in CH2Cl2/n-Bu4NPF6 by a spectroelectrochemical method. The medium was chosen to reduce the influence of disproportionation to the 1b and 1b2+ species. When the electrolysis of 1b was performed at

• Information File 1). When the electrolysis is performed at E1/22 + 0.15 V, the first band deriving from the π–π* transition of the NAr3•+ moiety increased in intensity (Supporting Information File 1, Figure S10), reflecting the presence of two chromophores in the generated two-electron-oxidized species 1b2

• ferrocenium moiety is accommodated largely on the d orbital, while that of the NAr3•+ moiety is delocalized from the nitrogen center to the benzene ring adjacent to the urea bridge. The MV species 1a+ and the dication 1a2+ were also generated by the controlled-potential electrolysis and characterized by UV

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• imidazopyridine-containing biaryls via central-to-axial chirality transfer (Scheme 1). Results and Discussion The substituents on the phenyl ring (R1) and at the propargylic position (R2) of carbamate 2 were varied to study their effects on the diastereoselectivity (Table 1). The electrolysis was conducted under

Reactions of 3-(p-substituted-phenyl)-5-chloromethyl-1,2,4-oxadiazoles with KCN leading to acetonitriles and alkanes via a non-reductive decyanation pathway

• Akın Sağırlı and
• Yaşar Dürüst

Beilstein J. Org. Chem. 2018, 14, 3011–3017, doi:10.3762/bjoc.14.280

• methods have been reported for the conversion of organic nitriles into the parent alkanes; such as oxidative decyanation [20], dehydrocyanation [21] and more commonly, reductive decyanation [22]. Among them, the reductive decyanation is a widely used method employing metal hydrides [23], electrolysis [24

Oxidative and reductive cyclization in stiff dithienylethenes

• Michael Kleinwächter,
• Ellen Teichmann,
• Lutz Grubert,
• Martin Herder and
• Stefan Hecht

Beilstein J. Org. Chem. 2018, 14, 2812–2821, doi:10.3762/bjoc.14.259

• unequivocally proven by a preparative electrolysis of Z-sDTE66-PhCN and subsequent product analysis, showing a closed to Z-isomer ratio of 69:31 (Figure S43, Supporting Information File 1). Interestingly and in strong contrast to the Z-isomer, for the E-isomer a reversible reduction wave was observed and no

Learning from B₁₂ enzymes: biomimetic and bioinspired catalysts for eco-friendly organic synthesis

• Keishiro Tahara,
• Ling Pan,
• Toshikazu Ono and
• Yoshio Hisaeda

Beilstein J. Org. Chem. 2018, 14, 2553–2567, doi:10.3762/bjoc.14.232

• also described, with a focus on radical-involved reactions in terms of organic synthesis. Keywords: dehalogenation; electrolysis; green chemistry; heptamethyl cobyrinate; methyl transfer; 1,2-migration; photosensitizer; vitamin B12; Review 1. Introduction 1-1. Redox and coordination chemistry of B12

• -migration of carboylic ester (80%) and some simple reduction product (20%) were obtained under controlled-potential electrolysis at −2.0 V vs SCE in the presence of catalyst 1 in DMF (Scheme 1b) [54]. There were different ratios for the simple reduced product and the ester-migrated product, depending on the

• bulkiness, the yields of the migrated products are higher for the smaller ester group [55]. Furthermore, we succeeded in tuning selectivity in the 1,2-migration of a functional group mediated by 1 by controlling the electrolysis potential (Scheme 2) [56]. The electrolysis of diethyl 2-bromomethyl-2

Direct electrochemical generation of organic carbonates by dehydrogenative coupling

• Tile Gieshoff,
• Vinh Trieu,
• Jan Heijl and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2018, 14, 1578–1582, doi:10.3762/bjoc.14.135

• technology [11][12]. Several groups developed interesting protocols to use electrochemistry for carbonate generation, but these approaches suffer from complex electrolysis set-ups and lack in scalability [13][14][15][16][17][18][19][20]. In this context, we decided to focus onto a novel electrochemical

• Within initial experiments the anodic electrolysis of benzene in an aqueous media with metal carbonate salts was investigated. Due to the challenging combination of both, benzene and carbonate source in sufficient concentration within the electrolyte, first experiments were not successful. Benzene

• mixed carbonates [33]. Electrolysis experiments were conducted in undivided 5 mL beaker-type cells. Initial studies with benzene as the aromatic compound in acetonitrile in the presence of the described methyl carbonate salt did not result in the desired organic carbonate. Polymerization of the benzene

Cobalt–metalloid alloys for electrochemical oxidation of 5-hydroxymethylfurfural as an alternative anode reaction in lieu of oxygen evolution during water splitting

• Jonas Weidner,
• Stefan Barwe,
• Kirill Sliozberg,
• Stefan Piontek,
• Justus Masa,
• Ulf-Peter Apfel and
• Wolfgang Schuhmann

Beilstein J. Org. Chem. 2018, 14, 1436–1445, doi:10.3762/bjoc.14.121

• with the same electrode. Electrolysis of HMF using a CoB modified nickel foam electrode at 1.45 V vs RHE achieved close to 100% selective conversion of HMF to FDCA at 100% faradaic efficiency. Keywords: alternative anode reaction; electrocatalysis; electrosynthesis; HMF oxidation; hydrogen evolution

• large scale electrochemical hydrogen production. Advantageously, the oxidation of an alternative substrate at the anode, for example a biomass-derived fuel, allows to generate high value products besides hydrogen concomitantly with an increase in energy conversion efficiency during electrolysis [4

• ]. Evidently, as already seen during RDE voltammetry the presence of HMF allowed an oxidation process to occur prior to the OER. However, neither the degree of oxidation, product distribution nor the reaction pathway for HMF oxidation can be resolved from voltammograms. Constant potential electrolysis at 1.45

Spectroelectrochemical studies on the effect of cations in the alkaline glycerol oxidation reaction over carbon nanotube-supported Pd nanoparticles

• Dennis Hiltrop,
• Steffen Cychy,
• Karina Elumeeva,
• Wolfgang Schuhmann and
• Martin Muhler

Beilstein J. Org. Chem. 2018, 14, 1428–1435, doi:10.3762/bjoc.14.120

• influence on the water electrolysis on Pt(111) [28] and Ir(111)/oxide electrodes [29]. Different Pt single crystal surfaces [30] and other electrochemical reactions such as CO [30], formate [31] and ethylene glycol oxidation [32][33] were studied as well. Especially for these more complex oxidation

• found for Au electrodes in the case of ethanol and methanol oxidation [26] and H2O electrolysis in alkaline media [28]. In our case using CNT-supported Pd NPs, the observed cation-related activity trend suggests another reason due to the differently functionalized CNT surfaces. Gosselink et al. [40

Stereoselective nucleophilic addition reactions to cyclic N-acyliminium ions using the indirect cation pool method: Elucidation of stereoselectivity by spectroscopic conformational analysis and DFT calculations

• Koichi Mitsudo,
• Junya Yamamoto,
• Tomoya Akagi,
• Atsuhiro Yamashita,
• Masahiro Haisa,
• Kazuki Yoshioka,
• Hiroki Mandai,
• Koji Ueoka,
• Christian Hempel,
• Jun-ichi Yoshida and
• Seiji Suga

Beilstein J. Org. Chem. 2018, 14, 1192–1202, doi:10.3762/bjoc.14.100

• pool” method can realize the generation and accumulation of highly reactive cationic species such as N-acyliminium ions in relatively high concentrations by low temperature electrolysis [6][7][8][9][10]. The N-acyliminium ions thus generated can directly react with a variety of carbon nucleophiles to

• -phenyl-2,3,4,5-tetrahydropyridin-1-ium (C1) derived from precursor 1a and ArS(ArSSAr)+ (Ar = p-FC6H4) generated by the low temperature electrolysis was first performed with several nucleophiles (Table 1). The starting 1a and other N-acyliminium ion precursors were synthesized by the modified Beak’s

• protocol [12] (see Supporting Information File 1). As observed in our previous studies, the Boc protecting group was found not suitable for the direct cation pool method due to its cleavage by protic acid generated during the electrolysis of the cation precursor. However, it can be utilized in the indirect

Polysubstituted ferrocenes as tunable redox mediators

• Sven D. Waniek,
• Jan Klett,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2018, 14, 1004–1015, doi:10.3762/bjoc.14.86

• correlated with the sum of Hammett constants. The 1/1+–4/4+ redox couples are chemically stable under the conditions of electrolysis as demonstrated by IR and UV–vis spectroelectrochemical methods. The energies of the C=O stretching vibrations of the ester moieties and the energies of the UV–vis absorptions

• are: (i) Both components of the redox couple should be soluble. (ii) Homogeneous and heterogeneous electron-transfer (ET) reactions should be fast. (iii) Both components should be stable under the electrolysis conditions and should not react irreversibly with any component of the supporting

• spectroelectrochemical (SEC) cell, confirming the chemical stability of the ferrocenyl esters under the conditions of electrolysis (Figure 3b, Figure 4, Figures S7–S14, Table S1, Supporting Information File 1). Triester 3 and tetraester 4 cannot be quantitatively oxidized to 3+ and 4+ in the SEC cell up to a potential

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• solution (Pt cathode) yields selectively 2-ethynylnaphthalene or 2-(bromoethynyl)naphthalene in high yields, depending on the electrolysis conditions. In particular, by simply changing the working potential and the supporting electrolyte, the reaction can be directed towards the synthesis of the terminal

• corresponding carbanion and halogen anion, can be achieved by a bielectronic cathodic process (Scheme 2). The electrolysis is carried out at a suitable controlled potential, i.e., at a potential that is negative enough to achieve the selective fission of the envisaged C–halogen bond [23]. Therefore, the

• -dibromoalkenes in the presence of acetic acid. The electrolysis conditions in this transformation were optimized in order to avoid or minimize the formation of the terminal alkyne. The latter was obtained as the major product in the absence of a proton donor and its formation could be suppressed when performing

Anodic oxidation of bisamides from diaminoalkanes by constant current electrolysis

• Tatiana Golub and
• James Y. Becker

Beilstein J. Org. Chem. 2018, 14, 861–868, doi:10.3762/bjoc.14.72

• : anodic oxidation; bisamides; constant current electrolysis; methoxylation; Introduction It is well known that the anodic oxidation of amides involving a hydrogen atom at the α-position to the N atom could undergo alkoxylation, carboxylation and hydroxylation at this position [1][2][3][4][5] (Scheme 1

• (Scheme 5). The selectivity of the anodic process was found to be highly dependent on the electrolyte used, and to a lesser extent, on the substrate concentration. Notably the importance of the former parameter in electrolysis has been well documented [15][16]. More recently the effect of the functional

• properties of α,ω-bisamides derived from α,ω-diaminoalkanes. However, notably that the bisamide 3,5-diaza-2,6-heptanedione was obtained from N-methylacetamide by electrolysis on a Pt anode in water [20]. The present work describes the electrochemical behavior of eight synthesized bisamides (from diamines

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• molecule 5. In this letter we report the electrochemical behavior of thiocarbonates 4 and 6 in aqueous methanol MeOH/H2O (80:20) with 0.5 M AcOH/AcONa buffer as supporting electrolyte, as well as the results of several reductive electrolysis performed under green chemistry conditions. Cyclic thiocarbonate

• −1.6 V, respectively (Figure 1), indicating the possibility of reducing these compounds in two electrochemical steps under the selected conditions. In order to determine which functional group is reduced, an electrolysis using 0.25 mmol of compound 4 was carried out under controlled potential after the

• classical Corey–Winter reaction. When potential-controlled electrolysis (PCE) is used a particular functional group in a molecule, in this case the thiocarbonate vs the α,β-unsaturated ester, can be selectively reduced. Under PCE feasibility and affordability of the reaction are limited by the potentiostat

Functionalization of N-arylglycine esters: electrocatalytic access to C–C bonds mediated by n-Bu₄NI

• Mi-Hai Luo,
• Yang-Ye Jiang,
• Kun Xu,
• Yong-Guo Liu,
• Bao-Guo Sun and
• Cheng-Chu Zeng

Beilstein J. Org. Chem. 2018, 14, 499–505, doi:10.3762/bjoc.14.35

• undivided cell under constant current electrolysis. It was observed that n-Bu4NI promotes the reaction dramatically and higher yields of α-functionalized products were afforded compared with the direct electrolysis. Results and Discussion Initially, N-arylglycine ester 1a and C–H nucleophile 1,3,5

• -trimethoxybenzene (2a) were chosen as model compounds to optimize the electrolytic conditions. As shown in Table 1, when constant current electrolysis (CCE) of 1a and 2a was performed in an undivided cell equipped with 0.1 M LiClO4 in CH3CN in the presence of AcOH using two graphite plates as anode and cathode, the

• method to the CDC reaction. In addition, it was observed that the electrocatalytic process is superior to the direct electrolysis. Further application of this electrochemical protocol for the formation of new C–C bonds is still on the way in our group. Experimental Instruments and reagents All melting

The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives

• Shunsuke Kuribayashi,
• Tomoyuki Kurioka,
• Shinsuke Inagi,
• Ho-Jung Lu,
• Biing-Jiun Uang and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2018, 14, 389–396, doi:10.3762/bjoc.14.27

• -fluorination. Based on these findings, we anticipated that the α-cationic intermediate could also be generated anodically from S-alkyl benzothioates. Moreover, we previously successfully carried out an anodic fluorodesulfurization of S-aryl thiobenzoates, and found that the indirect electrolysis using a

• triarylamine mediator gave much better yields of benzoyl fluorides compared to the direct electrolysis [23]. Therefore, we became interested in the anodic behavior of S-alkyl benzothioates in the presence of fluoride ions. With this in mind and in order to provide an additional application of our

• electrolytic conditions. Electrolysis was performed at a constant current (40 mA) with platinum electrodes (2 cm × 2 cm) in several solvents containing various fluoride salts in an undivided cell at room temperature and current was passed basically until 1a was consumed. The results are summarized in Table 1

Synthesis of naturally-derived macromolecules through simplified electrochemically mediated ATRP

• Paweł Chmielarz,
• Tomasz Pacześniak,
• Katarzyna Rydel-Ciszek,
• Izabela Zaborniak,
• Paulina Biedka and
• Andrzej Sobkowiak

Beilstein J. Org. Chem. 2017, 13, 2466–2472, doi:10.3762/bjoc.13.243

• ) (PtBA) side arms was synthesized via a simplified electrochemically mediated ATRP (seATRP), utilizing only 78 ppm by weight (wt) of a catalytic CuII complex. To demonstrate the possibility of temporal control, seATRP was carried out utilizing a multiple-step potential electrolysis. The rate of the

• polymerizations was well-controlled by applying optimal potential values during preparative electrolysis to prevent the possibility of intermolecular coupling of the growing polymer arms. This appears to be the first report using on-demand seATRP for the synthesis of QC-(PtBA-Br)5 pseudo-star polymers. The

• -defined star-like polymers, consisting of a quercetin core and hydrophobic PtBA arms with narrow MWDs by ATRP under multiple-step potential electrolysis conditions. Results and Discussion A flavonoid-based macromolecule initiator with 5 Br atoms (QC-Br5) was synthesized by the transesterification reaction