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

• bearing a perfluoroalkyl or perfluoroacyl group [27][28][29][30]. Furthermore, they extended this methodology to tandem cyclization to provide fused difluoromethylene-containing heterocycles [31]. In consideration of these facts, we studied the cathodic reduction of 1 using a mediator. Indirect cathodic

Synthesis of novel alkynyl imidazopyridinyl selenides: copper-catalyzed tandem selenation of selenium with 2-arylimidazo[1,2-a]pyridines and terminal alkynes

• Mio Matsumura,
• Kaho Tsukada,
• Kiwa Sugimoto,
• Yuki Murata and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 863–871, doi:10.3762/bjoc.18.87

• reagents and 1,3-dipolar azide–alkyne cycloaddition based on the alkyne moiety. Keywords: alkynyl imidazopyridinyl selenide; copper catalyst; imidazo[1,2-a]pyridine; selenium; tandem reaction; terminal alkyne; Introduction Imidazo[1,2-a]pyridines are important heterocycles that serve as key functional

• this study, the synthesis route still has some limitations such as the yields of alkynyl imidazopyridinyl selenides and the scope of substrates. Nevertheless, the scope of future research includes the application of this synthesis route using other heterocycles, and the investigation of the biological

• regioselective 1,3-dipolar azide–alkyne cycloaddition to form 5-selanyl-1,2,3-triazole. The investigation of the biological activity of the compounds obtained in this study and the application of this synthesis route using other heterocycles, instead of imidazopyridine, are currently underway in our laboratory

Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons

• Hengjia Liu and
• Guohua Xie

Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83

• fluorescent materials containing Lewis basic nitrogen heterocycles are more likely to provide the feasible band gap modulation. The essence of such phenomenon originates from Lewis acid–base coordination and adducts, which highly depends on the electron-accepting property of the Lewis acids. This

• of nitrogen-containing heterocycles in the fluorescent materials, the addition of a Lewis acid tended to induce red-shifted absorption and emission, shedding light on the fact that the Lewis acid interacts easily with the nitrogen-containing fluorescent materials. This interaction mechanism is the

• nitrogen-containing heterocycles, resulting in the change of energy levels and spectra. The following will illustrate Lewis acids used in the exploration of luminescent materials and mechanisms due to Lewis acid–base interactions. The chemical structures of some candidate Lewis acids are shown in Figure 1

Thiophene/selenophene-based S-shaped double helicenes: regioselective synthesis and structures

• Mengjie Wang,
• Lanping Dang,
• Wan Xu,
• Zhiying Ma,
• Liuliu Shao,
• Guangxia Wang,
• Chunli Li and
• Hua Wang

Beilstein J. Org. Chem. 2022, 18, 809–817, doi:10.3762/bjoc.18.81

• )2-bb-DSS, the notation bb means that the positions of the heteroatoms of the outer two heterocycles are on the same side as those of the middle heterocycle. Taking dithienothiophene as example, according to the positions of sulfur atoms, there are six isomers of dithienothiophene, in which the

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• experimentally observed stereoselectivity. Keywords: azomethine ylides; cycloaddition; cyclopropenes; DFT calculations; spiro heterocycles; Introduction Spiro compounds (molecules containing at least two rings with only one common atom) are an important class of both synthetic and naturally occurring

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

• , they are often used in heterocycles formation [8][9], multicomponent strategies [10][11], polymers production [12][13], and metal complexation [14][15]. The molecular structure is composed of an N–C planar triple bond where the nitrogen atom assumes a positive charge due to the fourth bond with a

• -methylimidazole were carried out, the outcomes were not as good as those already documented with pyridine in the literature. Possible explanations for this phenomenon are either a different electronic distribution between the two heterocycles or the absence of intermolecular interactions caused by the solvent

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

• technique can be easily automated. Thus, protocols can be iteratively repeated by simply changing building blocks so that compound libraries can be quickly accessed [54][55]. The formation of heterocycles traditionally often requires very harsh conditions, so that high pressure and high temperature can

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

• ten innovative technologies that IUPAC recognized [7]. To perform organic transformations in a greener way, the mechanochemical methods can also be considered as one of the alternative approaches [8][9][10]. The one-pot multicomponent synthesis of important heterocycles can be the state of art

• direct C–H amination is vital to provide many amine derivatives by sustainable methods [36][37]. The dehydrogenative C–N cross-coupling reactions from unreactive N–H and C–H bonds can lead to various nitrogen-containing heterocycles [32][38]. Herein, we disclose the DDQ-mediated oxidative C–N coupling

Synthesis of sulfur karrikin bioisosteres as potential neuroprotectives

• Martin Pošta,
• Václav Zima,
• Lenka Poštová Slavětínská,
• Marika Matoušová and
• Petr Beier

Beilstein J. Org. Chem. 2022, 18, 549–554, doi:10.3762/bjoc.18.57

• synthesis of these heterocycles is rather challenging, because the fused pyran and furanone system cannot be easily prepared by standard cyclization methods [15][16][17]. Although karrikins are extremely active plant growth regulators [14][18][19], their biological activity in humans was not investigated

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• position 1 of the pyrazole ring with the aim to obtain new compounds with antimalarial and/or anti-SARS-CoV activity. Polyhalo-1,3-butadienes, carrying at least one nitro group, are valuable starting materials for the directed synthesis of highly functionalized heterocycles. During the past years, we have

• persubstituted pyrazoles were unknown until now. In addition, it is known that polyhalogenated nitrobutadienes are versatile synthetic precursors for many bioactive heterocycles such as insecticidal neonicotinoids [34]. Evaluation of biological properties Antibacterial and cytotoxic properties The general

Substituent effect on TADF properties of 2-modified 4,6-bis(3,6-di-tert-butyl-9-carbazolyl)-5-methylpyrimidines

• Irina Fiodorova,
• Tomas Serevičius,
• Rokas Skaisgiris,
• Saulius Juršėnas and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 497–507, doi:10.3762/bjoc.18.52

• ]. Moreover, the number and nature of various side units on the emitter framework can also affect the properties of TADF compounds [3]. Among the electron-donating units, 9,10-dihydroacridine, carbazole or phenoxazine derivatives often are used as D units, while the π-electron-deficient nitrogen heterocycles

• of aryl moieties into methylthio-substituted nitrogen heterocycles such as tCBz-mPYR are a Ni(0)-catalyzed cross-coupling reaction with Grignard reagents [34][36] or the Liebeskind–Srogl reaction employing arylboronic acids [37][38][39]. Taking into account a large assortment of arylboronic acids and

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• ; 3,4,5-trisubstituted isoxazoles; Introduction Isoxazoles are a privileged class of five-membered heterocycles, which are found in numerous bioactive natural products [1][2] and synthetic small molecule drugs [3][4], and are used as important precursors for the synthesis of β-hydroxycarbonyl compounds

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

• reaction, among pericyclic reactions, is a very important synthetic approach to obtain several molecular scaffolds, including naturally occurring molecules, drugs, polymers, and heterocycles with promising biological activity. Especially, Diels–Alder reactions involving quinones and dienes as starting

• outcome, although electronic effects can be considered to play a role, especially with substituted α-amino acids. Lanfranchi and co-workers also studied the menadione (10) alkylation by oxidative decarboxylation using carboxylic acids containing nitrogenous heterocycles as substituents, and achieved very

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

• which realizes for the construction of medium-sized saturated nitrogen heterocycles [21]. Although the process enables the rapid construction of saturated nitrogen heterocycles from acyclic precursors, it requires homogeneous precious transition metal complexes as photocatalysts. On the other hand

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

• Jonali Das Sajal Kumar Das Department of Chemical Sciences, Tezpur University, Napaam, Tezpur-784028, Assam, India 10.3762/bjoc.18.33 Abstract Indole-3,4- and 4,5-fused carbo- and heterocycles are ubiquitous in bioactive natural products and pharmaceuticals, and hence, a variety of synthetic

• an SEAr reaction as the ring-closure step can generate indole 3,4-fused cabo- and heterocycles or/and their indole 4,5-fused counterparts (Scheme 1B). This is primarily due to the fact that such substrates have two proximal nucleophilic sites: the indole C5 as the ortho position and intrinsically

• -unsubstituted, 4-substituted indoles have recently been successfully applied in the construction of indole 3,4- and 4,5-fused carbo- and heterocycles. Notably, most of these reactions are highly to completely regioselective, despite having two potential ring-closure sites in the substrates. From these reports

New efficient synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines through a Passerini/Staudinger/aza-Wittig/addition/nucleophilic substitution sequence

• Long Zhao,
• Mao-Lin Yang,
• Min Liu and
• Ming-Wu Ding

Beilstein J. Org. Chem. 2022, 18, 286–292, doi:10.3762/bjoc.18.32

• reaction has also been utilized widely in preparation of various heterocycles under mild neutral conditions [30][31][32]. Recently we have reported the synthesis of 3H-2-benzoxepin-1-ones, 4H-3,1-benzoxazines and oxazoles by combination of a Passerini with an intramolecular aza-Wittig reaction [33][34][35

• ]. Continuing our interest in the synthesis of N-heterocycles via the aza-Wittig reaction and multicomponent reactions [36][37][38], we wish to report herein a facile synthesis of polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines via sequential Passerini/Staudinger/aza-Wittig/addition

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• approach. This entails the use of a heated packed-bed reactor filled with solid K2CO3 as a base. Using DMSO as solvent, this flow method generates the target heterocycles within short residence times of 10 minutes and in yields up to 93%. Scale-up of this flow process was achieved (34 mmol/h) and featured

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

• -oxazoles [34][35]. This study aimed to develop and synthesize methyl 5-(cycloaminyl)-1,2-oxazole-4-carboxylates, as new amino acid-like building blocks. This type of functionalized heterocycles could exhibit not only useful biological properties, but also find application as building blocks for the

• correlates with the literature data [49]. In addition, there were some marginal differences between the bond lengths in the two 1,2-oxazole rings. Conclusion A series of novel 1,2-oxazole-4-carboxylate derivatives possessing Boc-protected 4-, 5- and 6-membered saturated nitrogen heterocycles were synthesized

Chemoselective N-acylation of indoles using thioesters as acyl source

• Tianri Du,
• Xiangmu Wei,
• Honghong Xu,
• Xin Zhang,
• Ruiru Fang,
• Zheng Yuan,
• Zhi Liang and
• Yahui Li

Beilstein J. Org. Chem. 2022, 18, 89–94, doi:10.3762/bjoc.18.9

• , heterocycles, such as carbazole, can also be used as nucleophiles in this reaction. Keywords: indole; N-acylation; nucleophilic substitution; thioesters; Introduction Molecules containing N-acylindoles have attracted wide attention in the synthetic polymers and pharmaceutical industry because of their unique

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• biological activities [6][7]. Moreover, they can be used as starting substances for different heterocycles, as precursors for the synthesis of polymers, as potential pharmacons, for the synthesis of natural products or analogues, and also as building blocks in drug research [8][9][10][11]. Furthermore, some

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• -2-yl)alkanamides and 1-(oxazolin-2-yl)alkylphosphonates. Keywords: aziridine; diazooxoester; diazo compound; ketene; oxazoline; ring expansion; Introduction Oxazoline derivatives are an important class of nitrogen and oxygen-containing five-membered unsaturated heterocycles [1] and widely exist in

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

• intracellular ROS and includes inhibition of tubulin polymerization (Scheme 9). Semicarbazides and thiosemicarbazides are substances used to identify aldehydes and ketones, are very versatile in the synthesis of heterocycles, and have several applications in the preparation of important drugs. Nucleophilic

• % yield (Scheme 11) [89]. Modifications in β-carbonyls 1,2-Naphthoquinone derivatives can be obtained through modifications in the carbonyls, leading to the formation of new compounds containing different groups, such as hydroxylamines, oxiranes, hydrazones, and heterocycles. These modifications can be

• involving the addition of arylamines to β-NQS 18 followed by N-alkynylation and then Cu(I)-catalyzed heterocyclization with tosyl azide in toluene at room temperature, leading to triazoles 50c–k in moderate to excellent yields (Scheme 14). The research group that most explored the formation of heterocycles

A two-phase bromination process using tetraalkylammonium hydroxide for the practical synthesis of α-bromolactones from lactones

• Yuki Yamamoto,
• Akihiro Tabuchi,
• Kazumi Hosono,
• Takanori Ochi,
• Kento Yamazaki,
• Shintaro Kodama,
• Akihiro Nomoto and
• Akiya Ogawa

Beilstein J. Org. Chem. 2021, 17, 2906–2914, doi:10.3762/bjoc.17.198

• facilitate the industrial use of α-bromolactones as important intermediates. Keywords: α-bromolactone; metal-free; one-pot operation; tetraalkylammonium hydroxide; two-phase system; Introduction Lactones are important heterocycles in the organic chemistry, materials science, and medicinal chemistry fields

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

• 166 which is oxidized by Fe(III) to a carbocation species 167. Subsequent attack by the nitrile affords the nitrilium ion 168 which upon hydrolysis gives the final product 164. Oxime esters and ethers represent a widely used starting material for the generation of nitrogen-containing heterocycles. Due

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• of natural product-like compound libraries. Keywords: [bis(trifluoroacetoxy)iodo]benzene PIFA; nitrogen heterocycles; oxidative cyclization; pyrrolo[1,2-a]quinazolines; Introduction An important design concept in current drug discovery includes structural modifications of naturally occurring

• )-ones 7 upon action of bis(trifluoroacetoxy)iodobenzene (PIFA) (see Scheme 1D). A part from the well-known applications of hypervalent iodine compounds for oxidative rearrangements, fragmentations, halogenations and hydroxylations [37][38], they were also involved in the synthesis of N-heterocycles [39

• nitrogen atom to nitrenium intermediates occurred initially; further stabilization of these species resulted in the formation of hydroxylated lactams [44][45][46][47][48], azaspirocycles [49][50][51][52][53], or tricyclic nitrogen-containing heterocycles [44][53]. Our study commenced with the synthesis of