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

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• versatile starting materials in organic synthesis [1][2]. Specifically, due to their keto–enol tautomerism and high reactivity, diketones are excellent precursors for different pharmaceuticals [3]. Cyclic 1,3-diketones have been widely exploited to access enantiomerically enriched scaffolds with increased

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• Information File 258: General information, synthesis procedures, and spectral data. Acknowledgements The authors are grateful to Mr. S. Belyakov (Latvian Institute of Organic Synthesis, Riga, Latvia) for performing the X-ray analysis. Funding This work has been accomplished with financial support provided by

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• Fluminense, Faculdade de Farmácia, Departamento de Tecnologia Farmacêutica, 24241-000, Niterói-RJ, Brazil 10.3762/bjoc.18.5 Abstract Several low molecular weight naphthoquinones are very useful in organic synthesis. These compounds have given rise to thousands of other naphthoquinones that have been tested

• used in organic synthesis, they are excellent analytical derivatization reagents to spectrophotometrically determine drugs containing primary and secondary amino groups. This review summarizes the literature involving β-NQS. Keywords: biological activities; derivatization reagents; β-NQS; organic

• new fragments in the general structure or modifying functional groups. In Figure 1, eight low molecular weight naphthoquinones are highlighted, which are the most commonly used in organic synthesis. Among them, quinones 1–5 are naturally occurring, are simple to prepare and are commercially available

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• -aryl-substituted cyclic tertiary amines including N-arylpiperidines and N-aryltetrahydroisoquinolines. The high reusability of the catalyst at least seven times further enhanced the importance of this strategy in the field of organic synthesis. 1.2 Cyanation of amines using homogeneous catalysts An

Stepwise PEG synthesis featuring deprotection and coupling in one pot

• Logan Mikesell,
• Dhananjani N. A. M. Eriyagama,
• Yipeng Yin,
• Bao-Yuan Lu and
• Shiyue Fang

Beilstein J. Org. Chem. 2021, 17, 2976–2982, doi:10.3762/bjoc.17.207

• obtained. However, for many other applications, which include as linkers in organic synthesis and bioconjugation [8], as ingredients in nanomedicines to stabilize nanoparticles and to assist nanoparticle cell entry [9][10][11], and as PEGylation agents to stabilize drugs based on biologic molecules such as

• protecting groups would be preferred. Such routes can double the length of the PEG in three easy steps and the PEG product is asymmetric. It is noted that the use of base-labile protecting groups or linkers in organic synthesis involving carrying out reactions under less basic reactions and removing the

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• catalysts is desirable from both an ecological and economic standpoint. Certainly, in the past couple decades, iron has become a key player in the development of sustainable coupling chemistry and has become an indispensable tool in organic synthesis. Over the last ten years, organic chemistry has witnessed