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

• sequences, these strategies enable advancements in reaction scalability as well as tunability. Having described the research that has been conducted to achieve suitable ‘electrical’ replacements of conventional ‘chemical’ organic transformations, it is clear that the establishment of stereoselective

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

• András György Németh,
• György Miklós Keserű and
• Péter Ábrányi-Balogh

Beilstein J. Org. Chem. 2019, 15, 1523–1533, doi:10.3762/bjoc.15.155

• characterized by 1H NMR, 13C NMR, HRMS and melting point. After the successful application of various nucleophiles, it was our intention to investigate the scalability of the procedure. Thus, a twenty-fold scale-up of the reaction between the isocyanide 1a, sulfur and methanol (2a) was performed (Scheme 5). In

Hoveyda–Grubbs catalysts with an N→Ru coordinate bond in a six-membered ring. Synthesis of stable, industrially scalable, highly efficient ruthenium metathesis catalysts and 2-vinylbenzylamine ligands as their precursors

• Kirill B. Polyanskii,
• Kseniia A. Alekseeva,
• Pavel V. Raspertov,
• Pavel A. Kumandin,
• Eugeniya V. Nikitina,
• Atash V. Gurbanov and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2019, 15, 769–779, doi:10.3762/bjoc.15.73

• alkaline media in a total yield of 61–73% (Table 2). It should be noted that the above-described method was useful for the synthesis of styrenes in quantities of up to 100 g (or even more, if necessary). This scalability was purposefully demonstrated by the multigram synthesis of 5e (see Experimental part

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• reproducibility, ease of product purification, scalability of the reactions and versatility of the substituents introduced. Specifically, the prepared ditosylated β-CDs were separated using preparative reversed-phase column chromatography and their structures were elucidated by NMR experiments. Azidation led to

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• reactions in larger scale, e.g., the synthesis of β-ketoenamides KE35 that was prepared in 3.5 g quantity [34]. The scalability of the three-component reactions seems therefore no problem which is important for the multistep preparation of subsequent products (see below). Aromatic dinitriles such as 1,3

Assembly of fully substituted triazolochromenes via a novel multicomponent reaction or mechanochemical synthesis

• Robby Vroemans,
• Yenthel Verhaegen,
• My Tran Thi Dieu and
• Wim Dehaen

Beilstein J. Org. Chem. 2018, 14, 2689–2697, doi:10.3762/bjoc.14.246

• salicylaldehydes are used. Complementary to this the one-pot three-component reaction gave better results for liquid salicylaldehydes. In order to show the utility of the developed methodologies towards possible drug discovery, the scalability of the reactions was explored (Scheme 4). Both developed methodologies

Microfluidic light-driven synthesis of tetracyclic molecular architectures

• Javier Mateos,
• Nicholas Meneghini,
• Marcella Bonchio,
• Nadia Marino,
• Tommaso Carofiglio,
• Xavier Companyó and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2018, 14, 2418–2424, doi:10.3762/bjoc.14.219

• spanning from 41% to 72% (Figure 3). In order to demonstrate the easy scalability of the present method (Scheme 1) two MFPs were used in a parallel setup producing 948 mg of 4a after 14 h with an overall productivity rate of 0.196 mmol·h−1 [15]. Subsequently, a series of manipulations were conducted on

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• , authentically mild conditions (40 °C stirring) as well as practical scalability. Keywords: additive-free; catalyst-free; cycloaddition; enaminones; on water; 1,2,3-triazole; Introduction Discovering sustainable chemical syntheses constitutes one central issue of modern organic chemistry. A large number of

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• reaction specifically investigated the dimerization of thiols. Some of the experiments carried out by the group were in a flow chemistry set up, exemplifying the scalability of the procedure. In addition, the oxidant that achieves the transformation is molecular oxygen, making this a very sustainable route

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

Mild and selective reduction of aldehydes utilising sodium dithionite under flow conditions

• Nicole C. Neyt and
• Darren L. Riley

Beilstein J. Org. Chem. 2018, 14, 1529–1536, doi:10.3762/bjoc.14.129

• chemicals increasing lab safety and direct scalability. These are all beneficial in moving towards more efficient and sustainable techniques in chemical processing [3][4][6][7]. The reduction of carbonyl groups are a standard type of transformation in organic synthesis, however, to date under flow

Nanoreactors for green catalysis

• M. Teresa De Martino,
• Loai K. E. A. Abdelmohsen,
• Floris P. J. T. Rutjes and
• Jan C. M. van Hest

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

• industry. A number of reasons can account for this. First of all, the construction of the nanoreactors is not always a cost-efficient process. Scalability and reproducibility in nanoreactor production also are key factors that have to be addressed. The recyclability and cost price should be improved to

Investigating radical cation chain processes in the electrocatalytic Diels–Alder reaction

• Yasushi Imada,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 642–647, doi:10.3762/bjoc.14.51

• ). We finally turned our attention to the scalability of the reaction. On the basis of the above discussed radical cation chain mechanism, even higher concentrations of the substrates would still be effective (Table 2). To our delight, a high current efficiency of around 5000% was maintained even at 1.0

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• rapid reaction [44]. In this field, flow reactors offer benefits in terms of mass and heat transfer, both enhanced by the geometry of the reactor. Furthermore, the possibility to have a continuous production and to easily perform multiple modular reactions, leads to the improved scalability of these

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• bromides proceeded smoothly to form the corresponding products. A late-stage trifluoromethylation of an estradiol derivative and a gram-scale reaction were performed with this protocol demonstrating the applicability of this protocol to other pharmaceutically relevant molecules and its scalability

Main group mechanochemistry

• Agota A. Gečiauskaitė and
• Felipe García

Beilstein J. Org. Chem. 2017, 13, 2068–2077, doi:10.3762/bjoc.13.204

• obtained in small-scale via salt metathesis reactions due to poor starting material (SrI2 and K[Cp′]) solubility in ether solution. LAG provides a high yielding synthetic methodology circumventing the scalability issues associated with the inefficient diffusion of reactants in large-scale solution-based

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• transformation of 8a to the sultam 10a was achieved (Table 1, entries 8, 9). To demonstrate the scalability of this synthesis of the sultam 10a, the reaction was carried out with 7.1 g of 8a and just 2 mol % of Pd(OAc)2, to furnish an isolated yield of 4.3 g (83%) of the sultam 10a. Under the optimized reaction

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• significant catalytic activity (yield = 38%). Finally, to test the scalability of the process, a set of reactions was carried out increasing the amount of substrate rac-1a under the optimized reaction parameters. (Table 4). Relative to the results obtained with 1 equivalent of rac-1a in the presence of LAG

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• in 2010 was developed with a main focus on scalability. Alternative access routes to key fragments allowed the efficient synthesis of multigram quantities of late stage intermediates. Finally, 1.3 g of the highly pure extended mycolactone core were prepared. Kishi’s 1st generation synthesis of the

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• formed in high yields and selectivity. While the overall sequence towards 5 consequently required twice a two-step adaption of the oxidation state which renders this route quite lengthy, the authors argue that the robustness, facile conduction and scalability of each step was very high and made them

Fast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction

• Qi An,
• Youssef Hassan,
• Xiaotong Yan,
• Peter Krolla-Sidenstein,
• Tawheed Mohammed,
• Mathias Lang,
• Stefan Bräse and
• Manuel Tsotsalas

Beilstein J. Org. Chem. 2017, 13, 558–563, doi:10.3762/bjoc.13.54

• solid liquid interfacial layer-by-layer (LbL) synthesis of CMP-nanomembranes via Cu catalyzed azide–alkyne cycloaddition (CuAAC). However, this process featured very long reaction times and limited scalability. Herein we present the synthesis of surface grown CMP thin films and nanomembranes via light

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

• acknowledged as viable and very often superior alternative to batch processing. Continuous-flow techniques offer increased safety, scalability, reproducibility, automation, reduced waste and costs, and accessibility to a wide range of new chemical possibilities, seldom not accessible through classic batch

A chemoselective and continuous synthesis of m-sulfamoylbenzamide analogues

• Arno Verlee,
• Thomas Heugebaert,
• Tom van der Meer,
• Pavel I. Kerchev,
• Frank Van Breusegem and
• Christian V. Stevens

Beilstein J. Org. Chem. 2017, 13, 303–312, doi:10.3762/bjoc.13.33

• the direct scalability of the developed protocol. For these reactions the required amount of product was aimed at 100–200 mg which took about 3 hours of production. Compound 3cb, which corresponds with AK-7, was also produced on gram scale which took approximately 24 hours. Table 5 shows 15 analogues

NMR reaction monitoring in flow synthesis

• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2017, 13, 285–300, doi:10.3762/bjoc.13.31

• applications even for NMR metabolomics [26]. Stripline coils represent a simple and effective coil design with interesting applications even as detectors in DNP methods [22][27]. Stripline coils produce high and homogeneous B1 field, can be integrated on a microfluidic chip and show scalability as reported by

Continuous-flow synthesis of highly functionalized imidazo-oxadiazoles facilitated by microfluidic extraction

• Ananda Herath and
• Nicholas D. P. Cosford

Beilstein J. Org. Chem. 2017, 13, 239–246, doi:10.3762/bjoc.13.26

• using polar organic solvents such as dimethylformamide (DMF) [7][8][9][15]. However, the challenges of removing large amounts of high boiling solvents during the purification and isolation process can limit scalability and efficiency. Furthermore, many useful synthetic reactions are incompatible with

• multistep continuous-flow method allowed the construction of complex molecules rapidly without the need for purification and isolation of intermediates, lower flow rates and small reactors limited the scalability of the method. As noted previously, the use of high boiling point solvents, such as DMA, are