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

• diphenylamines yielding N,N-diarylbenzidines and N,N-diaryldihydrophenazines were reported in [21]. By varying the reaction conditions and additional substituents in the phenyl rings, a possibility for the selective oxidation of ortho-(2-pyridyl)diphenylamine to the corresponding nitroxide, as well as the

• the post-electrolysis mixture. Instead, a complex mixture of products was obtained. It looks as if the oxidation is non-selective; not a single reaction path dominates. This is typical for diarylamines containing electron-withdrawing substituents in both rings; commonly, electrochemical oxidation

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• De Esch et al. [55] and by Kazuta el al. [56]. The primary aim was the design of a new class of highly H3-selective agonists lacking H4 affinity by restricting the flexibility of the aminoethyl chain. Previous structure–activity exercises demonstrated an impact on selectivity upon introducing a

• studies. Thiazoles: 2-Thiazolylethylamine was characterized as a more selective and potent histamine H1 agonist [70]. Based on this, Govoni et al. [71] analyzed the pharmacological profile of several histamine H1 antagonists, with a section covering thiazole-based compounds. 2-(Thiazol-4-yl)ethylamine (99

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

• compatibility of the GBB reaction with typical KTGS conditions, such as aqueous solvent at near-physiological pH and high dilution, and the achievement of selective ligand amplification. First, molecular modeling studies were carried out to verify that building blocks and intermediates could bind the target

• cyclophanyl-imidazole-based library of ligands. The synthesis of ligands based on the [2.2]paracyclophane (PCP) moiety, thanks to its structural features and inherent planar chirality upon selective substitution, has been recently reviewed by the same author [46]. Starting from 4-formylcyclophane 37, a GBB

• multistep procedure, however, by employing 3,6-diamino-1,2,4-triazin-5-one 44 as amidine derivative, 46 could be simply obtained through a GBB-3CR. The amino group in position 3 was opportunely protected to drive the GBB reaction to the selective formation of 45. Microwave heating appeared to be beneficial

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

• . Lanthipeptide biosynthetic genes have undergone complex evolutionary processes that have produced chemically diverse active peptides [11][12]. These genes are predominantly found in bacteria and have evolved through selective pressures driven by competition for resources and defense against predators [13]. The

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• to be overoxidized and provided only traces of multiple products. Some overoxidation of 4d was observed as 12-methoxychrysene-5,6-dione (10), but the alternative product chrysene-6,12-dione was not formed. In contrast to the ortho-selective oxidations of PAPs with SIBX [18], the electrochemical

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

• 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

• cyclopamine. Comparing the biological results of the compound with the activity of desmethylveramiline (a des-E analogue of cyclopamine) has suggested that the rigidity of the oxetane ring is crucial for the potency of compound 7 [12]. Spiro-β-lactone steroids Beller et al. reported a selective method for

• 9763), displaying selective antifungal activity akin to nystatin, alongside with low cytotoxicity on cancer cell lines (HeLa, MDA-MB-453, and MDA-MB-361). Additionally, they exhibited robust activity against leukemia K562 cells [51]. Spiro-1,2,4-triazolidin-3-one steroids Sharma et al. developed a

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• toward developing a chemo-enzymatic synthetic process. Presumably, the reactive iron(IV)-oxo species in dioxygenase BscD abstracts an allylic hydrogen at C1 and generates intermediate A. Subsequent α-face-selective hydroxylation of the resulting allylic radical at the C3 position would yield brassicicene

• skeletal rearrangement, providing the distinct skeleton of 11 via carbocation C. This rearrangement involves the preferential migration of an alkenyl group in C to the carbocation, followed by deprotonation at C18 to form an exo-olefin. β-face-selective hydroxylation at C12 in 11 by the P450 enzyme BscG

• on a decagram scale in five steps from (+)-limonene oxide (13), involving epoxide manipulation, oxidative cleavage, and intramolecular aldol condensation. Similarly, the right-half fragment, allyl chloride 16, was synthesized from limonene in five steps. Site-selective hydrogenation, oxidative

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

• established in several oxidative transformations including the synthesis of complex molecules and drugs [12][13]. The most prominent examples are the pentavalent derivatives 2-iodoxybenzoic acid (IBX) and Dess–Martin periodinane (DMP) [14][15]. Although mild and selective oxidants, these highly oxidized λ5

• 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

• iodanes (NHIs) as effective λ3-iodane oxidants for the selective synthesis of ketones and aldehydes, avoiding overoxidation to carboxylic acids. The developed protocols proved particularly effective for benzylic alcohols, yielding good to excellent results. The beneficial role of chloride salt additives

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• bond to create new connections has attracted increasing interest [1]. While past methods allowed for C–H transformations in simple molecules, recent synthetic protocols [2] enable selective C–H activation and diversification in larger molecules. This has, for example, attracted the pharmaceutical

• pharmaceutical intermediates that undergo selective borylation to compare our QM workflow and ML model with experimentally determined reaction sites. The quantum chemistry-based workflow Following work by Ree et al. [12][13][14][15], we present a fully automated QM-based workflow for computing C–H pKa values. A

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• (Figure 1a). Upon 625 nm red-light irradiation for 60 s at 20 °C to reach the photostationary state (PSS), the strong absorption band at 470–685 nm was diminished, with a clear isosbestic point at 259 nm (Figure 1a, red line), which indicates a selective photoisomerization process from the open-isomer O

•  1d and Figure 1f, blue line), the strong absorption band had recovered and indicated a selective photoisomerization process from the open-isomers O-DA7 and O-DA6 (Figure 1c–f, black and blue lines) to the cyclized-isomers C-DA7 and C-DA6 (Figure 1d and Figure 1f, red line). The results showed

• the absorption band at 430–800 nm decreased and that at 250–325 nm increased. At the same time, isosbestic points were clearly observed at 286 nm, 357 nm, and 443 nm (Figure 2a, red line). The results indicated a slower selective photoisomerization process from O-DA11 to C-DA11 in aqueous medium

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• straightforward conditions (Scheme 1). The synthesis of aryl halides is of great academic and industrial importance. Recently, our research group has developed a new procedure for the ortho-selective chlorination of phenols under mild conditions in a short reaction time [26]. The chlorinating species was

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• Ana Flavia Candida Silva Francisco A. Martins Matheus P. Freitas Department of Chemistry, Institute of Natural Sciences, Federal University of Lavras, 37200-900, Lavras, MG, Brazil Department of Chemistry, University of Houston, Houston, TX, USA 10.3762/bjoc.20.140 Abstract Selective fluorination

• stereochemical behavior. Consequently, various molecular properties, such as polarity, viscosity, and intra- and intermolecular interactions, are impacted by the C‒F bond. These features underlie the important role of selective fluorination in pharmaceuticals and agrochemicals development [1]. For instance

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• aryl halides [42]. PEM reactors are also gaining industrial attention. Weber et al. reported a series of large-scale syntheses using PEM reactors [43]. We studied electrochemical transformations [44][45][46][47][48][49] and recently reported the selective reduction of enones using a PEM reactor [50

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

• Alexander P. Atkins Alice C. Dean Alastair J. J. Lennox University of Bristol, School of Chemistry, Bristol, BS8 1TS, U.K. 10.3762/bjoc.20.137 Abstract The selective fluorination of C(sp3)–H bonds is an attractive target, particularly for pharmaceutical and agrochemical applications. Consequently

• , over recent years much attention has been focused on C(sp3)–H fluorination, and several methods that are selective for benzylic C–H bonds have been reported. These protocols operate via several distinct mechanistic pathways and involve a variety of fluorine sources with distinct reactivity profiles

• compound, carry that functional group through synthesis and also protect any potentially labile group that would otherwise displace during the installation of the fluorine atom [6][7][8]. Therefore, methodologies for the selective C–H fluorination represent a valuable class of reactions [1][9][10], for

Tetrabutylammonium iodide-catalyzed oxidative α-azidation of β-ketocarbonyl compounds using sodium azide

• Christopher Mairhofer,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1510–1517, doi:10.3762/bjoc.20.135

• Bu4NI allowed for the clean and selective formation of 1a, we observed significant amounts of the α-I-ketoester 3 when using KI instead. Having established the combination of DBPO and Bu4NI as the best-suited catalyst/oxidant combination for the α-azidation of 1a using NaN3, we finally optimized

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• -selective manner with moderate levels of enantioselectivities (up to 83:17 er). Furthermore, the obtained products can be successfully engaged in nucleophilic ring opening reactions, thus giving highly functionalized α-amino acid derivatives. Keywords: allenoates; amino acids; azlactones; organocatalysis

• studies we also realized that the masked β-AA derivatives 2 undergo enantioselective β-addition to allenoates 3 under chiral ammonium salt catalysis (Scheme 1B) [18]. Interestingly, hereby we also found that the use of alternative catalyst systems (i.e., tertiary phosphines) allows for a γ-selective

• thus wondering if we could extend this ammonium salt-catalyzed β-selective allenoate functionalization strategy to other amino acid classes. Azlactones 1 have previously been used for γ-selective additions to allenoates under chiral phosphine catalysis [28]. In addition, glycine Schiff base derivatives

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• equivalents of dihydroxyazobenzene 6 were used for the selective monoglycosylation step, with the excess of azobenene being recovered after column chromatography. Under these conditions, no bisglycosylated azobenzene was observed [28]. The observed 1,2-trans glycosylation could be explained either by the

• with the surface. Due to enthalpy–entropy compensation, that is a general effect in protein–carbohydrate interactions [41], this does not reflect in differences in affinity. However, these observations, together with future modeling studies, will help in designing new compounds with more selective

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• reactions. Therefore, electrochemical polymerizations can be utilized for selective synthesis. Cyclic oligosaccharides are an important class of host molecules, and some natural cyclic oligosaccharides are produced by enzymatic processes. However, the corresponding chemical syntheses are still primitive [6

• effect. Although glycosyl donors with an N3 group in position C-2 have been used for α-selective glycosylation [20][21], we have already found that β-selective glycosylation proceeds using a glycosyl donor with an N3 group under electrochemical conditions [22]. The results of the electrochemical

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• intermediates through selective FeCl3-catalyzed intramolecular N-annulation. Keywords: α-aminoacetals; fused-ring systems; heterocyclic hemiaminals; heterocyclic N,O-aminals; multicomponent reactions; Introduction N-Fused heterocycles are ubiquitous within crucial molecules, including biologically active

• process and developed a catalytic system-controlled selective intramolecular N-annulation process for ring-fused biheterocyclic N,O-aminal derivatives as stable imine equivalents and useful tools for new bond formation in view of further fused-heterocylization processes. Moreover, control experiments

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• . Acknowledgements We thank Dr. Yong W. Kim (University of Toledo) for NMR assistance. Mr. Babatunde Obadawo (University of Toledo) is acknowledged for collecting the high-resolution mass spectrometry data. We acknowledge Dr. Navdeep Kaur’s Ph. D. for her contributions in her Ph. D. thesis titled “Selective

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• hybrids. The selective N-functionalization of the triazene-protected pyrazoles was conducted, and the cleavage of triazenylpyrazoles to the corresponding azides was described for the first time with regioisomer 17, whereas regioisomer 18 is acid-insensitive and cannot be converted. The azides were reacted

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• also simplifies product isolation and purification and improves the overall sustainability of the process [23][24]. However; specific reaction requirements ensure efficient and selective utilization of solvents. Marvi and Talakoubi carried out the Cannizzaro reaction [25] using montmorillonite K-10 and

• ability to introduce carboxylic acid functionalities and facilitate functional group interconversions makes it a valuable method for chemists engaged in the design and synthesis of diverse organic compounds. A selection of applications is depicted herein. Mehta et al. established a highly selective

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• a methoxy group were transformed into the products in good yields (3la–na). 4-(Trifluoromethoxy)iodobenzene also well participated in this reaction, affording 3oa in 65% yield. Aryl iodides having fluoro and chloro substituents underwent selective C–I bond cleavage to provide monoalkylated products

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• -induced cyclization of the eunicellane skeleton (Figure 2). When 1 and 2 were individually subjected to acidic conditions (i.e., TFA in CHCl3), both cyclized into 6/6/6-tricyclic skeletons via a selective C2–C7 cyclization after protonation at C6 to give trans-BC ring systems (i.e., cis,trans-6/6/6 for 1

• . Scaffold exploration of the eunicellane skeleton During protonation-induced cyclization of 1 and 2, the C6–C7 alkene showed higher nucleophilicity than either of the other two double bonds likely due to the unique conformation of the eunicellane skeleton. This selective reactivity was further supported

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113