Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

• Wei-Hsin Hsu,
• Susanne Reischauer,
• Peter H. Seeberger,
• Bartholomäus Pieber and
• Dario Cambié

Beilstein J. Org. Chem. 2022, 18, 1123–1130, doi:10.3762/bjoc.18.115

• ; heterogeneous catalysis; metallaphotoredox catalysis; packed bed; photochemistry; Introduction The amount and impact of visible-light-mediated protocols in organic synthesis have increased dramatically since the late 2000s [1]. The main driving force of this phenomenon is the novel reactivity afforded by

• [4][5]. This is underlined by several photochemical and photocatalytic transformations that have been performed on industrial scales in continuous-flow reactors [6][7][8]. A particularly appealing branch of photocatalytic organic synthesis is the combination with other modes of catalysis in dual

• visible-light photocatalysts that enable new reaction pathways that were previously difficult or impossible to realize [2]. Technical advancements, such as the rise of light-emitting diodes (LEDs) and new reactor technologies were similarly important incentives to popularize light-mediated organic

Electrogenerated base-promoted cyclopropanation using alkyl 2-chloroacetates

• Kouichi Matsumoto,
• Yuta Hayashi,
• Kengo Hamasaki,
• Mizuki Matsuse,
• Hiyono Suzuki,
• Keiji Nishiwaki and
• Norihito Kawashita

Beilstein J. Org. Chem. 2022, 18, 1116–1122, doi:10.3762/bjoc.18.114

• organic synthesis as versatile building blocks [1][2][3][4][5]. In general, some synthetic procedures for cyclopropane derivatives have been discovered, e.g., the Simmons–Smith reaction and the use of metal carbenoids being two of the more prominent and reliable methods [6][7][8][9]. Aggarwal and

Electrochemical hydrogenation of enones using a proton-exchange membrane reactor: selectivity and utility

• Koichi Mitsudo,
• Haruka Inoue,
• Yuta Niki,
• Eisuke Sato and
• Seiji Suga

Beilstein J. Org. Chem. 2022, 18, 1055–1061, doi:10.3762/bjoc.18.107

• reactor; Introduction Catalytic hydrogenation of α,β-enones is a significant transformation in organic synthesis [1]. Hydrogenation of enones can give ketones, allyl alcohols, and saturated alcohols, and the control of the chemoselectivity is important. Therefore, there have been numerous studies on the

• environmentally benign organic transformations. Despite these advantages, the utility of PEM reactors in precise organic synthesis has long been unclear. Recently, however, Atobe and co-workers showed that PEM reactors can be used as a powerful and novel tool for precise organic synthesis [22][23][24][25][26

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• in organic synthesis and sometimes appear in biologically active compounds, pharmaceuticals, agrochemicals and functional molecules, amidomethylation induced by N-acyliminium ions is a helpful and valuable protocol for direct introduction of an amide function into organic molecules. Generation of N

• has also been applied to organic synthesis [17][18][19][20]. However, when electrochemical oxidation of amides/carbamates in the presence of nucleophiles, such as electron-rich arenes or silyl enol ethers, is carried out for Friedel–Crafts-type amidomethylation, electrochemical oxidation of electron

• amidomethylated products in good to high yields. Keywords: electrochemical oxidation; Friedel–Crafts type amidomethylation; N-acyliminium ion; quasi-divided cell; trialkylammonium salt; Introduction Oxidation of amides generates useful intermediates, N-acyliminium ions, which have been widely used in organic

Electrochemical vicinal oxyazidation of α-arylvinyl acetates

• Yi-Lun Li,
• Zhaojiang Shi,
• Tao Shen and
• Ke-Yin Ye

Beilstein J. Org. Chem. 2022, 18, 1026–1031, doi:10.3762/bjoc.18.103

• ; Introduction Organoazides play important roles in pharmaceutical, bioorthogonal chemistry, and many other interdisciplinary research areas [1][2][3]. Among them, azidoketones are also very versatile building blocks in organic synthesis, pharmaceutical, and materials science [4][5][6]. Therefore, the

First example of organocatalysis by cathodic N-heterocyclic carbene generation and accumulation using a divided electrochemical flow cell

• Daniele Rocco,
• Ana A. Folgueiras-Amador,
• Richard C. D. Brown and
• Marta Feroci

Beilstein J. Org. Chem. 2022, 18, 979–990, doi:10.3762/bjoc.18.98

• scale up. In the case of the flow procedure, a 0.1 M solution of the IL is employed, which may be more convenient than using pure ILs. Further investigations of electrogeneration of NHCs and applications in organic synthesis are underway. Experimental Materials and methods Chemicals were purchased from

Cathodic generation of reactive (phenylthio)difluoromethyl species and its reactions: mechanistic aspects and synthetic applications

• Sadanobu Iwase,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2022, 18, 872–880, doi:10.3762/bjoc.18.88

• , these methods require various metal and organometallic reagents. On the other hand, electrochemical organic synthesis is a metal-free process and does not require any hazardous reagents and it produces less waste than conventional chemical syntheses. Therefore, electrochemical synthesis is desirable

Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• provide great potential for applications in organic synthesis, pharmaceutical chemistry and materials science. Experimental 1. General procedure for the preparation of the spiro[carbazole-3,3'-inolines] 1a–j and 1a’–j’: A mixture of 2-methyl-1H-indole (0.5 mmol, 1.0 equiv), aldehyde (0.6 mmol, 1.2 equiv

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• synthesis of odorants is the only way to provide them in sufficient quantities when natural sources are rare, or their production is unethical as it is the case for ingredients obtained from animals such as musk or civet [9][10]. In recent years, flow chemistry has enriched organic synthesis as an enabling

• organic synthesis that simplifies upscaling and, in some cases, allows to overcome limitations in batch, while being safer and more sustainable. These advantages have been utilized for the preparation of various odorants, reaching from fruity and green odorants, which are typically small and volatile

Complementarity of solution and solid state mechanochemical reaction conditions demonstrated by 1,2-debromination of tricyclic imides

• Petar Štrbac and
• Davor Margetić

Beilstein J. Org. Chem. 2022, 18, 746–753, doi:10.3762/bjoc.18.75

• , irradiation and electrochemistry as methods of chemical activation [8]. Based upon our experience in applications of this method to organic synthesis [9][10][11][12], we recognized its potential for the adjustment of conditions in zinc-mediated debromination reactions. Highly reactive dienophiles such as

A trustworthy mechanochemical route to isocyanides

• Francesco Basoccu,
• Federico Cuccu,
• Federico Casti,
• Rita Mocci,
• Claudia Fattuoni and
• Andrea Porcheddu

Beilstein J. Org. Chem. 2022, 18, 732–737, doi:10.3762/bjoc.18.73

• first synthetic approaches were reported by Ugi and Hofmann (Scheme 1) [3][4], who described their characteristic odour as “horrible” and “extremely distressing”. With such a breakthrough, isonitriles gained wide popularity in organic synthesis due to their extreme versatility [5][6][7]. Especially

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• attention in the field of natural products and organic synthesis. In this review, we summarize the structural analyses, mechanistic investigations, and proposed reaction mechanisms of endoperoxide-forming oxygenases, including cyclooxygenase, fumitremorgin B endoperoxidase (FtmOx1), and the asnovolin A

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• chemistry, but also in medicine. Traditionally, inductive heating is used in industry, e.g., for heating large metallic objects including bending, bonding, and welding pipes. In addition, inductive heating has emerged as a partner for flow chemistry, both of which are enabling technologies for organic

• synthesis. This report reviews the combination of flow chemistry and inductive heating in industrial settings as well as academic research and demonstrates that the two technologies ideally complement each other. Keywords: catalysis; enabling technologies; flow chemistry; inductive heating; multistep

Rapid gas–liquid reaction in flow. Continuous synthesis and production of cyclohexene oxide

• Kyoko Mandai,
• Tetsuya Yamamoto,
• Hiroki Mandai and
• Aiichiro Nagaki

Beilstein J. Org. Chem. 2022, 18, 660–668, doi:10.3762/bjoc.18.67

• with good operational stability, evaluated by a constant high yield of cyclohexene oxide, to obtain the desired product with high productivity. Keywords: air; continuous flow; cyclohexene oxide; flow epoxidation; rapid gas–liquid reaction; Introduction From the past to the present, organic synthesis

• has contributed to the development of science and technology. With the rapid advances in the 21st century, increasing demand for organic synthesis has led to a strong need for faster and more sophisticated methods. The gas–liquid reaction is one of the organic synthetic methods of importance because

• the reaction with good efficiency [11][12]. The continuous flow technology has brought a dramatic change and new aspects in organic synthesis [13][14][15][16][17][18][19][20][21][22][23] and has been noticed to provide significant improvement in gas–liquid reactions [24][25]. Thus, we envisioned that

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• constructing C–N bonds are in high demand in organic synthesis since nitrogen-containing organic compounds are widely used in biologically active substances [1], multifunctional materials [2][3], and metal ligands [4][5]. Among them, the synthesis of aromatic amines has been important to researchers in recent

DDQ in mechanochemical C–N coupling reactions

• Shyamal Kanti Bera,
• Rosalin Bhanja and
• Prasenjit Mal

Beilstein J. Org. Chem. 2022, 18, 639–646, doi:10.3762/bjoc.18.64

• . Keywords: ball mill; 1H-benzo[d]imidazole; C(sp2)–H amidation; DDQ; mechanochemistry; quinazolin-4(3H)-one; Introduction The reawakening approaches to use solvent-free and environmentally benign conditions in organic synthesis have facilitated new opportunities [1][2][3][4]. The research area of

• moiety in 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), it was well established as a hydride transfer reagent in various organic reactions [14][15]. Generally, DDQ assists in dehydrogenation reactions in organic synthesis [16]. In this context, various carbon–heteroatom bond formation reactions such

• as C–P [17], C–O [18][19][20], and C–S [21] were achieved using DDQ as an oxidant [22][23]. In addition, the utilization of DDQ as a photoredox catalyst [24] and co-catalyst [25][26] have also been documented in organic synthesis [27]. DDQ-mediated oxidative C–N cross-coupling reactions are well

A study of the photochemical behavior of terarylenes containing allomaltol and pyrazole fragments

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2022, 18, 588–596, doi:10.3762/bjoc.18.61

• organic synthesis. Thus, an actual problem is to study the photochemical behavior of various compounds capable of photogeneration of these unstable intermediates. Moreover, the results of such investigations can be used for the development of UV-promoted synthetic methods. Among the photochemical

• processes used in organic synthesis, 6π-electrocyclization of 1,3,5-hexatriene systems is attracting considerable attention [10][11][12][13][14][15][16][17]. The photocyclization of terarylenes leading to the formation of polyheterocyclic compounds is one of the most widely studied processes of this type

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• used to access menadione derivatives, to highlight the importance of this substrate for organic synthesis. The most common reaction types and reaction sites of menadione derivatization are depicted in Figure 4. The vast majority of the methods involve the unsaturated α,β-system of the naphthoquinone

• attention in the last few years in organic synthesis due to its physical and chemical properties. The authors studied the Diels–Alder reaction between menadione (10) and 2,3-dimethyl-1,3-butadiene (51) and it was possible to draw a comparison between the reported properties for this type of solvent (Table 4

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• . Keywords: calix[4]pyrrole; chalcogen bonding; ketones; Se···O bonding interactions; supramolecular catalysis; Introduction Noncovalent catalysis has been established as one of the fundamental concepts in organic synthesis that enables achieving numerous chemical transformations [1]. Among these

• range of typical reactions [24], thus providing a new platform for organic synthesis. The phenomenon of chalcogen bonding was initially observed in the crystal structures of small organic molecules as well as proteins [25]. The application of this type of bonding interactions has achieved significant

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• constructing carbon–carbon and carbon–heteroatom bonds in organic synthesis [8][9][10]. In the course of their diversity-oriented synthesis of indole-based peri-annulated compounds, You and co-workers in 2013 reported the intramolecular Tsuji–Trost reaction of indolyl allyl carbonates 1 under the catalysis of

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• , Kottayam, Kerala, 686560, India 10.3762/bjoc.18.31 Abstract Iron- and cobalt-catalyzed Sonogashira coupling reactions are becoming central areas of research in organic synthesis. Owing to their significant importance in the formation of carbon–carbon bonds, numerous green and nanoparticle protocols have

• original Sonogashira coupling. Both, iron and cobalt catalysts are considered environmentally friendly as they are non-toxic and inexpensive, and thus have significance in modern organic synthesis. The use of an aqueous medium in Fe-catalyzed reactions represents the most reasonable and green option for

• 30 mol % of dmeda as ligand in toluene at 135 °C for 72 h (Scheme 7). On the other hand, acetylenes with alkyl substitution showed lower reactivity. In addition, to increase the importance of iron catalysts as a versatile tool in organic synthesis, a novel iron-catalyzed domino Sonogashira coupling

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study

• Angel Ho,
• Austin Pounder,
• Krish Valluru,
• Leanne D. Chen and
• William Tam

Beilstein J. Org. Chem. 2022, 18, 251–261, doi:10.3762/bjoc.18.30

• hydride, and C–C bond-forming reductive elimination. Computational results indicate the origin of regioselectivity is involved in the reductive elimination step. Keywords: C–H activation; density functional theory; hydroacylation; iridium catalysis; regioselectivity; Introduction Organic synthesis is

• the art and science of selective molecular engineering [1]. To date, organic synthesis has largely been governed by the interconversion of pre-existing functional groups through the use of more traditional transition-metal-catalyzed cross-coupling reactions [2][3][4][5]. Although these reactions have

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• Anna V. Korotina Svetlana G. Tolshchina Rashida I. Ishmetova Natalya P. Evstigneeva Natalya A. Gerasimova Natalya V. Zilberberg Nikolay V. Kungurov Gennady L. Rusinov Oleg N. Chupakhin Valery N. Charushin Laboratory of Heterocyclic Compounds, Postovsky Institute of Organic Synthesis, Russian

• studies were carried out using equipment of the Center for Joint Use “Spectroscopy and Analysis of Organic Compounds”, located in Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences. Funding This work was supported by the Ministry of Education and Science of the

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• . Most notably, this step can go through a liquid–liquid separation that requires multiple operations generating large amounts of waste notably arising from the different organic and aqueous layers. In the context of the development of more eco-compatible organic synthesis limiting the number of

• yield (Scheme 3). This highlights the potential of this technique for organic synthesis. Conclusion To conclude, we have disclosed a new approach considerably limiting waste and operations necessary for amine purification. Taking advantage of a temporary protonation with TCA, the solid amine salts

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• encountered in organic synthesis as precursors for the synthesis of nitrogen and oxygen-containing molecules [1][2][3][4][5]. The high reactivity caused by the polarization of the N–O bond enables the nitrosoarenes to undergo a wide range of transformations in a chemo- and regioselective manner [6][7][8]. The