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

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• stereoselective asymmetric synthetic methods to access 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides, and their fused and spiro derivatives are in high demand and should be developed in the near future. Biologically active 1,2-azaphospholine 2-oxide derivatives. Diverse synthetic strategies for

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

• groups in many biologically active substances and pharmaceuticals, such as zolpidem, alpidem, and GSK812397 [1][2][3]. Therefore, the development of multiple chemical modification methods, at the 3-position of the imidazo[1,2-a]pyridine skeleton, for the synthesis of 3-substituted-imidazo[1,2-a]pyridines

• concentrated under reduced pressure. The residue was purified by column chromatography using hexane/AcOEt as eluent to give the desired products 4aa–ma. Biologically active selenides having alkynyl or imidazopyridinyl groups. (a) ORTEP drawing of 4aa and (b) its stacking structure. Proposed mechanism. Control

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

• substances. Many biologically active natural products have a spirocyclic skeleton in their structure [1][2]. In this regard, there is interest in studying heterocyclic spiro compounds for drug discovery. These compounds were found to exhibit a broad range of biological activities, including antioxidant [3

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

• that play important roles in antimalarial activity by damaging membranes, inhibiting nucleic acid and protein syntheses, and so on [8][9]. The best studied endoperoxide-containing compound is probably prostaglandin H2 (PGH2), the common precursor of biologically active prostanoids [10][11][12

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• -coupling reactions [9][10][11][12][13][14][15][16][17][18][19] or components of pharmaceuticals and biologically active molecules [20][21]. The synthetic aspects of both approaches in solution are well established. The need for green and sustainable chemistry [22] has led to the development and synthetic

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

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• of this library will be reported in due course. Biologically active cholic acid hybridized with different heterocyclic scaffolds. Structures of target compounds 4a–v. Synthesis of cholyl 1,3,4-oxadiazole-2-thiol 2. Synthesis of cholyl 2-(propargylthio)-1,3,4-oxadiazole 3. Synthesis of target

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

• , natural products, and biologically active compounds such as pergolide, scopolamine, morphine, nicotine, hygrine, and procyclidine (Figure 1) [2][3][4]. Therefore, a considerable number of synthetic approaches to pyrrolidines and piperidines have been investigated [5][6][7][8][9][10][11][12][13

• with THF and analyzed using HPLC. Piperidine and pyrrolidine rings in biologically active compounds. Schematic diagram of the electroreductive cyclization for the synthesis of 1,2-diphenylpiperidine (3a) in an electrochemical flow microreactor. Adapted with permission from ref. [33]. Copyright 2021

Synthesis of 5-unsubstituted dihydropyrimidinone-4-carboxylates from deep eutectic mixtures

• Sangram Gore,
• Sundarababu Baskaran and
• Burkhard König

Beilstein J. Org. Chem. 2022, 18, 331–336, doi:10.3762/bjoc.18.37

• further chemical transformations on the DHPM skeleton. We hope that this environmentally benign one-pot method will find application in the synthesis of 5-unsubstituted dihydropyrimidinones. Biologically active functionalized DHPMs. Synthesis of 5-unsubstituted DHPMs.a Supporting Information Supporting

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

• polysubstituted 3,4-dihydroquinazolines and 4H-3,1-benzothiazines under mild reaction conditions is still of high demand in the discovery of biologically active compounds. The Passerini reaction is an isocyanide-based multicomponent reaction, which has been used in preparing various α-acyloxy adducts starting

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

• reported metal-catalyzed reactions of heterobicyclic alkenes and applications towards the synthesis of biologically active compounds (top). Representative examples of regioselectivity in different metal-catalyzed ring-opening reactions of C1-substituted oxabenzonorbornadiene derivatives (bottom left

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

• . Keywords: antifungal activity; nucleophilic substitution; oxidative cyclization; [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines; Introduction Azolo-annulated azines can be regarded as purine isosteres and are of great interest for modern medicinal chemistry as potential biologically active compounds. In

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

• biologically active reaction products, led us to explore the implementation of a continuous flow platform to reduce these hazards, while maintaining the high efficiency of the reaction. Results and Discussion We began with the investigation of various oxidative cyclisations of acyl hydrazones to compare 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

• , 2-oxobut-3-enoates [10]. A 1,2-dicarbonyl moiety is also an important structural fragment present in various natural products and biologically active compounds [11]. 1,2-Diketones have been used for the synthesis of photosensitive polymers [12] and substituted imidazoles [13][14] and have been used

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

• important class of heterocyclic compounds that plays a fundamental role in drug discovery [1][2][3][4][5][6][7]. Many amino-functionalized 1,2-oxazole derivatives are biologically active substances that include naturally occurring and synthetic neuroactive compounds. Specifically, natural products such as

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

• East Coast fever. This drug is effective in the treatment of cattle infected with Theileria annulata transmitted by the brown tick Rhipicephalus appendiculatans [34][35][36]. As part of our research program on the synthesis of biologically active quinones, we are interested in the synthesis and

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• biologically active natural products and pharmaceutical compounds with antipsychotic and antifungal activities, such as SB 209670, indatraline, tefludazine, mutisianthol, rasagiline, and ramelteon (Figure 1) [1][2][3][4][5]. Therefore, this structural motif has attracted great attention of researchers in the

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• biologically active molecules are currently being investigated in our laboratories. Some antitumor agents containing the 4-anilinoquinazoline moiety. Examples of N-arylation reactions using 4-chloroquinazolines as substrates. Synthesis of verubulin analog. Synthesis of 4-chloro-6-halo-2-phenylquinazolines 8a

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

• of functional groups with neither EDGs nor EWGs altering the reactivity of the acrylamide. Once synthesized, the authors demonstrated the oxindoles could be transformed into fused indoline–heterocycle frameworks in good yield, an attractive scaffold found in many biologically active compounds [119

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

• alkaloids – that can be used as building blocks to obtain natural product-like compound libraries of potential biologically active compounds. Experimental Commercially available reagents and solvents were used without further purification. The IR spectra of the compounds obtained were recorded on a Bruker

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• underway. Biologically active 1-aminoisoquinolines. Comparison of our work with the previous approaches for the synthesis of 1-aminoisoquinolines. Substrate scope of anilines for the synthesis of 1-aminoisoquinolines (5a–m). Reaction conditions: 3 (1 equiv), 4 (1.5 equiv), Me3Al (2 equiv) in toluene at 110

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• target product 69 (Scheme 23). This catalytic approach encompasses a wide range of substrates and functional groups to construct atropisomeric N-arylbenzimidazoles that are widely used in natural products, biologically active molecules, ligands, and catalysts. Axially chiral arylpyrroles are the core

• and could considerably improve the stereocontrol of the reaction [21]. The axially chiral arylquinazolinones form the backbones of a large number of natural products and biologically active compounds as well as chiral ligands [83]. Nevertheless, a simple chiral phosphoric acid-catalyzed

• and spiranes The enantioselective construction of spirocyclic centers is an exciting synthetic challenge that plays a prominent role in the discovery of new catalysts and complex molecules [98]. Spirocyclic frameworks are present, for example, in biologically active natural products (e.g

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• bile acids, derivatives with altered hydrophobicity are being studied [12][13][14]. The tetrazole moiety can be found in many biologically active compounds, and monosubstituted tetrazole is being used in medicinal chemistry as a bioisostere of carboxylic acid [15] because it increases the lipophilicity

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• 108 to aliphatic α,β-unsaturated aldehydes 109 and synthesized biologically active acyclonucleoside 110 via an iminium-ion activation mechanism. The initially formed product was reduced in situ to afford the final product in 82–89% yield and 89–96% ee (Table 25) [66]. In a similar method, Joie et al