Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• ]; (ii) the incorporation of the iodine atom in the 5-membered heterocycle [10]; and (iii) the trans effect, due to the interaction of the hypervalent bonds established by the axial ligands, where iodine orbitals are shared with both heteroatoms [11]. As a result, benziodoxol(on)es have found application

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• efficiencies in atom economy [3][4]. The extension of the reaction to an intramolecular version represents a viable approach for the construction of several fused-ring skeletons [5]. Such ring structures containing heterocyclic rings would be of crucial importance because heterocycle-fused ring structures [6

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• build the principal heterocycle of the compounds. Good reaction yields (70–87%) made it possible to obtain the aminothiophene carboxylates necessary for the following steps of the route [52]. Some of the intermediates of the Gewald reaction were oxidized to provide further exploration of the

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• this review aims to fill. The synthetic uses of HVI reagents [14][15][16], their involvement in heterocycle synthesis [17][18][19], and alkene functionalisation [20][21], have each been well-reviewed elsewhere. Review Hypervalent iodine-mediated fluorocyclisation Fluorine can substantially improve the

• . The authors proposed two possible mechanisms for the reaction (Scheme 24). Firstly, a chloronium ion is generated by HVI and LiCl followed by intramolecular nucleophilic attack by nitrogen to form the heterocycle. Secondly, oxidation of the unsaturated guanidine forms an intermediate aziridinium A

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• rigidity along the C–C bond between the heterocycle and ethene bridge due to the fused cyclic fragment. As a consequence of the additional ring, the fluorescence efficiency increased. At the same time, solid-state emission was observed due to the steric hindrance, which prevented intermolecular

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• this Li and Jiang, created an effective ball-milling process for the N-arylation of amines 38 with the assistance of diaryliodonium salts 16 (Scheme 15) [67]. The arylation of an amino group or nitrogen heterocycle occurred effectively when the reaction is performed under solvent-free conditions or

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• [48], switching catalyst to Pd(PPh)3, and base to Na2CO3 (Table 1, entry 16) gave no product. Ultimately, an increased catalyst loading of 25 mol % per C–Br bond gave the desired porphyrin in a 16% yield when using Cs2CO3 as base. The synthesis of other heterocycle-appended dodecasubstituted

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• established for these compounds. The electrochemical behavior of the studied compounds is influenced by several factors: the nature of the heterocycle and its substituents, the presence of a sulfur atom in the catechol ring, or a thione group in the heterocyclic core. The radical scavenging activity and

• possibility of alkylation of the nitrogen atom in the heterocycle cannot be excluded. This alternative pathway is similar to the previously described interaction of the aforementioned catechol with 3,5-dimethylpyrazole or benzimidazole [55]. A study of the structure, electrochemical properties, anti

• ). At the same time, the interaction of 2-mercapto-substituted derivatives of 1,3,4-oxadiazole or 1,2,4-triazole with the starting catechol proceeds at the nitrogen atom of the five-membered heterocycle due to the possibility of the thione–thiol tautomerism in the starting thiol [26][27]. Consequently

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• coupling reactions of the obtained compounds 2. It should be emphasized that amino-1,2,5-oxadiazoles correspond to very weak nucleophiles due to the highly electron-withdrawing effect of the heterocycle. Our previous efforts achieved a certain result indicating that (1,2,5-oxadiazolyl)diazonium salts

• , indicating that the developed tandem protocol does not depend on the presence of the N-oxide moiety in the parent heterocycle. All synthesized triazinones 1 and 7 were fully characterized by IR, 1H and 13C NMR spectroscopy, and high-resolution mass spectrometry. The structure of compounds 1b and 7h was

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• Federation Research Institute of Chemistry, Рeoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya Street, 6, Moscow, 117198, Russian Federation 10.3762/bjoc.20.188 Abstract A one-pot three-component synthesis of substituted meta-hetarylanilines from heterocycle-substituted 1,3

• desired meta-heterocycle aniline 3ag was prepared in low yield. Finally, the developed method is suitable for the late-stage arylation of drug-like molecules such as deacetyllinezolid (3ak). The meta-substituted anilines 3 are formed in a sequence of reactions shown in Scheme 6 [53]. Firstly, the reaction

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• reaction. At the same time, Bachi et al. succeeded in synthesizing a 5-membered nitrogen-containing heterocycle based on the 5-exo cyclization of isocyanides with alkenyl or alkynyl groups using thiols as mediators (Scheme 14) [57]. The generated thiyl radical attacks the isocyano group and forms imidoyl

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -acetoacetylcoumarin 41, 3-bromoacylpyran 42, and semicarbazide 40 (Scheme 12) [65]. Alternatively, the corresponding chromenes can replace the 3-bromoacylpyrans. A notable advantage of this process is its catalyst-free nature and the achievement of good regioselectivity. Due to the high heterocycle density, this

• reactions in heterocycle synthesis [163][164] and certainly also for substituted pyrazoles. Four classes of 1,3-dipoles are considered as synthetic equivalents for the CN2 synthon: diazo compounds [165], nitrilimines [166], sydnones [167], and azomethinimines [168]. These intermediates undergo (3 + 2

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• access to diazo compounds as either synthetic intermediates or products. A special attention is paid to the reaction mechanism with the aim to encourage further development in this field. Keywords: C–H functionalization; diazo compound; electrosynthesis; hydrazone; nitrogen-containing heterocycle

• hydrazones initiated with the SET anodic oxidation of the hydrazone and deprotonation to form the N-centered radical 10. After aza-cyclization on the aromatic ring, a second SET oxidation and deprotonation delivered the heterocycle 9. This mechanism was supported by cyclic voltammetry analysis of a model

• point of view, the authors proposed the formation of N-pyridyl radical 18 through the anodic oxidation of in situ-generated anion 17. Subsequent radical cyclization, second anodic cyclization and deprotonation yielded the fused heterocycle 16. Similarly, Youssef and Alajimi disclosed the electrochemical

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• indazoles would provide greater synthetic utility for this valuable heterocycle. These examples suggest a common intermediate such as methyl 5-bromo-1H-indazole-3-carboxylate (6) could be used to generate such compounds. An alkylation strategy that uses the vast array of commercially available alcohols as

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• electrode in MeCN solution using Bu4NBF4 as a supporting electrolyte. Oxidation of the salts occurs at high positive potentials (>2 V vs Ag/AgCl, KCl(sat.), Figure 1a), in accordance with the cationic nature of the heterocycle. In the negative potential range, an irreversible peak can be observed in the

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• (azetidin-2-one) scaffold to medicinal chemistry and drug design is self-evident. This four-membered heterocycle is a key fragment of many antibiotics [1], including penicillin and its analogues, as well as other pharmacologically important molecules [2]. Therefore, the search for new efficient and

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• subsequent sections. Influence of heterocycle type In this section, we focus on the character and type of the rings comprising the cc-hPASs, going from the broader perspective (size) to a more detailed view (aromatic/antiaromatic) and finally to the specific type of ring. Size of ring In the broadest sense

• in Supporting Information File 1, section 3.2.). Specific identity of heterocycle The previous analyses revealed two relationships: lower LUMO values were shown to correspond to both the presence of boron-containing rings and to the presence of antiaromatic rings. However, two-thirds of our

• shows scatter plots of the HOMO versus LUMO, each colored according to the presence of a specific type of heterocycle. To avoid ambiguity, only molecules that contain benzene and the heterocycle highlighted in the respective plot are colored (i.e., molecules that contain mixtures of heterocycles are not

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• several precursors, forming superclusters. The RiPPMiner platform [5] was used to predict in silico post-translational modifications of the mature lanthipeptides. Based on these predictions, several clusters did not contain precursor peptides with a predicted lanthipeptide heterocycle formation and were

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• , azomethines based on aromatic amines and substituted pyrrolecarbaldehyde [40] or pyrrolyl-β-chlorovinylaldehyde [39], contain several frequently encountered motifs in drugs and drug candidates – a pyrrole heterocycle and an azomethine C=N fragment (Figure 1) – and exhibit some biological activity. Thus, Ugi

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• order to improve the synthesis of this fused heterocycle, different strategies were tried, e.g., performing the Ugi reaction in different solvents (dichloromethane, ethyl acetate, methanol) to prevent the precipitation of benzodiazepine 5c, conducting the Ugi reaction in boiling methanol or treating the

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• predominant. The outlined synthetic procedures emphasize the pivotal steps for constructing the heterocycles, often accompanied by a detailed account of the overall synthesis pathway. The review encompasses innovative compounds, including bis-steroids linked by a spiro heterocycle and steroids conjugated to

• the future design of more potent and selective drugs. Keywords: biological activity; drug development; heterocycle; spiro steroid; synthetic transformations; Introduction Small-ring heterocycles constitute valuable scaffolds in medicinal chemistry for generating biologically active derivatives

• functional groups of the steroid involved in heterocycle formation. Many descriptions also include the parent steroid alongside the total steps required to synthesize the target compound. Furthermore, numerous compounds feature data regarding their biological activity, underscoring the remarkable potential

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• Thomas J. Kuczmera Pim Puylaert Boris J. Nachtsheim Institute for Organic and Analytical Chemistry, University of Bremen, Bremen, Germany Institute for Inorganic Chemistry and Crystallography, University of Bremen, Bremen, Germany 10.3762/bjoc.20.149 Abstract We present N-heterocycle-stabilized

• the corresponding carboxylic acids [16]. Additives such as bromide salts or Al2O3 can eliminate this problem and allow selective oxidation to some extent [17][18][19][20]. During the past years, N-heterocycle-stabilized iodanes (NHIs) were demonstrated as suitable tools for various applications among

• proved to be effective in a model oxidation reaction of n-octanol (2). Since previous investigations have repeatedly shown that the number of heteroatoms in the N-heterocycle correlates with the NHIs activity, a series of tetrazole- and tetrazine-substituted NHIs 1a–e was synthesized (Figure 2) [29][30

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• reaction is a three-component condensation of an α-amino heterocycle (e.g., 2-aminopyridine) 1, an aldehyde 2, and an isonitrile 3 providing the corresponding fused imidazoles (e.g., imidazo[1,2-a]pyridines) of general formula 4 (Scheme 1) [18][19][20][21]. Imidazo[1,2-a]pyridines and related heterocycles

• }). Some of these results (e.g., on the reactivity of aminopyrimidine derivatives) were in accordance with the previous literature data [21][29]. Meanwhile, electronic effects of the substituents in the amino heterocycle reported in the previous works were somewhat contradictory. Whereas for the NO2 group

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• ]. The authors proposed the formation of a charge-transfer complex between the heterocycle and Selectfluor, capable of promoting an ET/PT or PCET pathway to furnish the carbon-centred radical at the heterobenzylic position. Fluorine-atom-transfer with Selectfluor then afforded the desired product