Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• major products were phenyliodane 23, presumably a result of ligand exchange and reduction, and iodoalcohol 18. Different solvents, temperatures and activators were investigated and the results are shown in Table S3 in Supporting Information File 1. Fluorobenzene was only ever observed in trace amounts

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• undergo reversible chemical reduction processes, as determined by cyclic voltammetry in CH2Cl2 solvent (Figure 4). There are two factors at play. The imide substitution is impactful as the N-phenyl derivatives are roughly by 100 mV easier to reduce than the N-hexyl analogs. The anthracene scaffold also

• lends itself to a more facile reduction process, with an approximately 150 mV shift of the event toward more positive potentials for 8-R vs 7-R. When compared to other structural isomers, aromatic diimides with 5-membered cyclic imides tend to be slightly harder to reduce than those with 6-membered

• title compounds indicates that they are optically and electronically similar to previously reported naphthalene and anthracene diimides, absorbing/emitting light in the visible region and readily undergoing one-electron-reduction processes. As such, this work opens the possibility of incorporating the

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

• with a reduced reactivity in the synthesis of 3H-benzo[e][1,4]diazepin-5-ones, heterocycles previously synthesized by our research group through Ugi/Staudinger/aza-Wittig and Ugi/reduction/cyclization sequences, using 2-azidobenzoic [20] and 2-nitrobenzoic [21] acids, respectively. The first

• chromatography column, while the more eco-friendly second strategy needs an additional stage for the reduction of the nitro group on the Ugi adduct. In order to find a more efficient synthesis, we thought that the second nitrogen in the diazepine nucleus could be incorporated without the need of surrogates or

• reaction took place with a α,3-like relative configuration on the major diastereomer, similar to that obtained for the Ugi/Staudinger/aza-Wittig sequence and complementary to that observed for the Ugi/reduction/cyclization sequence (see Supporting Information File 1, Figure S2). With the aim of building

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

• showed irreversible oxidation processes within the oxidative potential window, scaling from 0.79 V to 1.10 V vs Fe/Fe+. The oxidation peak potential difference between isomers of chrysenols 3 and phenanthrols 6 was 20–310 mV. No reduction peaks were observed in the reverse scan in solutions of neither

• chrysenols nor phenanthrols, suggesting a chemically irreversible reaction of the radical cation intermediate with the ensuing product no longer being electrochemically active within the potential window of the CV scans. However, a reduction peak was observed for compound 1b (see Figure S2 in Supporting

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

• protecting group yielded the corresponding hydroxyalkynyl derivative 4. Subsequent Lindlar reduction resulted in the (Z)-alkene and a chemoselective tosylation of the primary alcohol led to the formation of tosylate 5. This intermediate underwent a stereospecific 4-exo cyclization upon exposure to iodine

• epoxide was then opened by treatment with sodium azide and boric acid, yielding the azide derivative 146 in 87% from estrone. A subsequent reduction of the azide with LiAlH4 provided the aminoalcohol derivative 147 in 64% yield. Then, a chloroacetamido moiety was formed at the amino function in 51% yield

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

• , and subsequent reduction of the exomethylene at C11–C18 catalyzed by BscH yield brassicicene O (12). Renata and co-workers successfully accomplished the chemoenzymatic total syntheses of cotylenol (1) and nine brassicicenes (Scheme 3) [19]. In the cyclization phase, a suitably functionalized 5/8/5

• evolution using site-saturation mutagenesis targeting the putative active sites L110 and Y112, led to the variant MoBsc9 Y112M, which substantially improved the enzymatic conversion into 22, achieving an isolated yield of up to 67%. Diastereoselective reduction of the C8 ketone was then achieved using the

• protocol of Nakada and co-workers [27], enabling the chemo-enzymatic total synthesis of cotylenol (1). Similarly, diastereoselective reduction of the C8 ketone in 20 yielded the biosynthetic intermediate 8 for brassicicenes. Although substrate 8 has a different oxidation state at C8 and lacks the C9

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

• known compounds, the generated GBB chemical space is unique as compared to the available compound collections. This fact is even more apparent from the t-distributed stochastic neighbour embedding (t-SNE) analysis, a technique widely used for the dimension reduction in data visualization [47]. Due to

• the relatively high computational costs of this method, we randomly selected 50,000 compounds to represent each database. The dimension reduction algorithm uses molecular features as the starting inputs to generate a few coordinates (in this case, t-SNE1 and t-SNE2) reflecting the probability of the

• (due to the large size of the dataset, a preliminary clusterization was performed to achieve ca. 5-fold size reduction); C) ZINC15 drug-like compounds, and D) enamine’s stock screening collection. Average T values are shown by dotted lines. t-Distributed stochastic neighbor embedding (t-SNE

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

• nitrogen atmosphere, followed by reduction of the indole motif in compound 1n to indoline in 2n. The ester group in compound 2n was deprotected under basic conditions to give compound 3n (Scheme 2). DAn with different chain lengths of the alkyl linker were synthesized through an aza-Piancatalli

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

• cyanoarenes, nitroarenes, quinolines, and pyridines using a proton-exchange membrane (PEM) reactor was developed. Cyanoarenes were then reduced to the corresponding benzylamines at room temperature in the presence of ethyl phosphate. The reduction of nitroarenes proceeded at room temperature, and a variety of

• anilines were obtained. The quinoline reduction was efficiently promoted by adding a catalytic amount of p-toluenesulfonic acid (PTSA) or pyridinium p-toluenesulfonate (PPTS). Pyridine was also reduced to piperidine in the presence of PTSA. Keywords: cyanoarene; nitroarene; PEM reactor; pyridine

• ; quinoline; Introduction Nitrogen-containing molecules are important bioactive compounds and intermediates in chemical synthesis. Therefore, the chemical transformations of nitrogen-containing compounds have been widely studied in the field of organic synthesis [1][2][3][4]. For instance, the reduction of

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

• ]. Photoexcitation of the Ir(III) catalyst I with blue light resulted in the photoexcited Ir(III)* catalyst, which was capable of performing a single-electron reduction on N-acyloxyphthalimide, promoting decarboxylation, releasing CO2, a methyl radical, anionic phthalimide and an Ir(IV) species. The resultant methyl

• , generated from reduction of tert-butyl benzoperoxoate (TBPB), selective benzylic HAT afforded the benzylic radical. Subsequent oxidation by Ir(IV) generated the benzylic cation that could be trapped by fluoride to afford the benzyl fluorides. An impressive scope with broad functional group tolerance

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• using acetonitrile as the solvent frequently led to the observation of Cu deposition at cathode (Table 1, entry 4). We reasoned that DMF could coordinate to the copper center, acting as a ligand to prevent copper from cathode reduction. Constant current electrolysis is also applicable to the reaction

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• PKSs. (b) Stereocontrol of KR domains. KRs can be classified into A-type (β-ʟ-hydroxy), B-type (β-ᴅ-hydroxy), and C-type (reduction-incompetent; β-keto) depending on the product structure and into subtypes 1 (non-epimerizing, α-ᴅ-substitution product) and 2 (epimerizing, α-ʟ-substitution product). (c

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• reduction. This electrophilic aromatic substitution usually needs harsh reaction conditions, tedious synthetic procedures and sometimes encounters the trouble of separating positional isomers caused by orientation or steric effects of the pre-existed amino group on the aryl moiety. Nevertheless, anilines

• are not always readily accessible. Typically, the preparation methods involve SNAr reactions with N-centered nucleophiles [5], nitroarene reduction [6] and transition metal (e.g., Pd, Cu)-catalyzed C–N cross coupling of aryl halides, aryl sulfonates or arylboronic acid reagents with ammonia or NH

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

• simplified form, focuses on the base-induced disproportionation of two molecules of a non-enolizable aromatic and/or aliphatic aldehyde (without an α-hydrogen atom). These aldehydes undergo in the presence of concentrated alkali or other strong bases, a simultaneous oxidation and reduction sequence of two

• flavoring agents, it plays a vital role for the development of unique sensory compounds [56][57]. The Cannizzaro disproportionation has also been observed in several electrochemical transformations [58] and during the electrocatalytic reduction of carbon dioxide [59]. A recent study by Liu et al. witnessed

• where other methods of oxidation or reduction might be challenging or impractical. The present discussion focuses on some recent synthetic advances and their application in biologically active compounds. Lewis acid-catalyzed intramolecular Cannizzaro reaction Wang et al. [73] depicted a highly

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• , the addition of the benzoyl radical to azobenzene results in the generation of a nitrogen-centered radical. This radical is then subjected to reduction by the reduced photocatalyst, producing the nitrogen-centered anion intermediate. Ultimately, the protonation of this anion gives rise to the desired

• prefunctionalized alcohols that are used under visible-light photoredox conditions to generate alkyl radicals by homolysis of C–O bonds. Thiocarbonyl: In 2014, Ollivier and co-workers [43] demonstrated visible-light-mediated iridium-catalyzed reduction of thiocarbonyl derivatives derived from alcohols. The

• final reductive elimination gives the desired alkene and Ni(I). The two catalytic cycles are finally completed by single-electron reduction of [Ni(I)] by [Ir(II)], which regenerates [Ni(0)] and ground-state [Ir(III)]. Cyclic oxalates readily form the corresponding alkyl radicals under iridium

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

• conditions. The key to success is the use of 1,3-dicyanobenzene as a redox mediator and visible-light irradiation, which effectively suppresses the formation of simple reduction, i.e., hydrodehalogenation, products to afford the desired products in good to high yields. Mechanistic investigations proposed

• beneficial features, such as higher chemical stability and wide commercial availability, compared with other precursors, e.g., diazonium salts [11]. Classical approaches toward aryl radical species from the corresponding halides would involve halogen abstraction or single-electron reduction processes using

• ][34][35][36]. In this context, the electrochemical single-electron reduction of aryl iodides, bromides, and activated (bearing at least one electron-withdrawing group) aryl chlorides has been demonstrated as a useful method to generate aryl radical species under mild reaction conditions [37]. Although

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• laboratory according to a previously published procedure [107]. The starting aminofuranes were easily prepared by reduction of Schiff bases (formed by condensation of the corresponding mono- or bis-amines with furfural) with sodium borohydride in methanol [83][108][109][110][111]. In order to determine the

Synthesis of indano[60]fullerene thioketone and its application in organic solar cells

• Yong-Chang Zhai,
• Shimon Oiwa,
• Shinobu Aoyagi,
• Shohei Ohno,
• Tsubasa Mikie,
• Jun-Zhuo Wang,
• Hirofumi Amada,
• Koki Yamanaka,
• Kazuhira Miwa,
• Naoyuki Imai,
• Takeshi Igarashi,
• Itaru Osaka and
• Yutaka Matsuo

Beilstein J. Org. Chem. 2024, 20, 1270–1277, doi:10.3762/bjoc.20.109

• molecular orbital (LUMO). To understand the electron affinity of t-Bu-FIDS, cyclic voltammetry was conducted. The cyclic voltammogram of t-Bu-FIDS in o-DCB showed reversible reduction waves at E1/2 = −1.14 V and −1.51 V (vs Fc/Fc+), as shown in Figure 3. Both the first and second reduction potentials of t

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• catalyst in the sulfonylation/arylation of styrenes and as a triplet sensitizer in energy transfer catalysis. The singlet lifetime is sufficiently long to exploit the exceptional excited state reduction potential for the activation of 4-cyanopyridine. Photoinduced electron transfer generating the radical

• /H2O (9:1). The low reduction potential of singlet-excited Aza-H (PC•+/PC* = –1.87 V vs SCE) led us to propose that the singlet-excited photocatalyst is oxidized by 4-cyanopyridine (4CP) (4CP/4CP•− = −1.81 V vs SCE) as the first step in this multicomponent reaction (Scheme 1, left). The oxidized

• -excited state lifetime), the quenching rate constant is roughly four orders of magnitude lower than singlet quenching (kq ≈ 105 M−1 s−1). This is in good agreement with the reported high triplet energy of 4CP [75] at 3.08 eV compared to 2.32 eV of 3Aza-H and the lower reduction potential provided by the

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• [30][31][32]. Due to the oxidative nature, the use as selenium source in the synthesis of arylchalcogen compounds, in particular diorganyl selenides, can be a challenging process that involves sequential formation of two C–Se bonds and reduction of a Se=O bond in a single-pot reaction. Further

• ]. This reaction comprises four main steps: (i) iodide-mediated aryl transfer from boronic acid to selenium dioxide, (ii) reduction of arylseleninic acid to diaryl diselenide, (iii) oxidation of diaryl diselenide to aryl selenenyl iodide with iodine, and (iv) electrophilic substitution of aniline

Two-fold addition reaction of silylene to C₆₀: structural and electronic properties of a bis-adduct

• Masahiro Kako,
• Masato Kai,
• Masanori Yasui,
• Michio Yamada,
• Yutaka Maeda and
• Takeshi Akasaka

Beilstein J. Org. Chem. 2024, 20, 1179–1188, doi:10.3762/bjoc.20.100

• irreversible, probably because of the removal of silylene addends, whereas the electrochemically reversible behavior was observed for the reduction waves. Table 2 presents the redox potentials of 3 obtained by DPV with those of C60 and 2, as reference compounds. Both the reduction (Ered) and the oxidation (Eox

• ) potentials of 3 were found to be shifted cathodically compared respectively to those of C60 and 2, indicating the electron-donating effects of the two Dip2Si groups. It is noteworthy that the first reduction potential of 3 (Ered1 = −1.52 V) is the most negative among those of the silylated empty fullerenes

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• ], Reformatsky reaction [65], azalactone synthesis [66], nitro reduction [67][68], epoxide rearrangement, thiourea guanylation, and others [69][70]. In this article, we describe a simple and direct protocol for the preparation of indanones through a classical Nazarov reaction catalyzed by bismuth(III) triflate

• ), and Bi(OTf)3 (0.05 mmol) were added to a sealed tube. The reaction mixture was stirred at 100 °C and monitored by TLC. Impact of indanone derivatives on cell viability of tumor cells. Cell viability was determined by MTT assay. Data is expressed as reduction in viability in relation to the vehicle

• , and the dotted line indicates 75% reduction in cell viability. Compounds that reduced cell viability by at least 75% at 5 µg/mL are highlighted in the graph. Previous methods describing decarboxylation reactions of indanones and xanthenones. Optimization of the reaction conditions. Evaluation of the

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• , hydroaminomethylation, reduction of nitriles and nitro compounds or through reductive amination of carbonyl derivatives [26][27][28][29][30]. However, for example, cross-coupling reactions with alkyl or aryl halides generate considerable amounts of waste (Scheme 2A). Even though many different approaches exist for

• condenses with hydrazine followed by reduction and condensation with another aldehyde to afford the N-substituted hydrazones (Scheme 8). Balaraman and co-workers established a phosphine-free manganese catalyst generated in situ from a manganese precursor and a ligand for the N-alkylation of anilines with

• step, reduction of unsaturated compounds with manganese hydride complexes giving the desired C-alkylated products. In 2016, Beller and co-workers introduced the first air-stable manganese(I)-PNP-pincer pre-catalyst for the α-alkylation of ketones with primary alcohols [57]. The reaction conditions were

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• racemisation, and nucleoside 14 with the same α/β ratio of 3:2 formed from either anomerically pure 17 or from a mixture of the anomers. Catalytic hydrogenation is usually used for the removal of benzyl protecting groups. However, standard hydrogenation conditions using 10% Pd/C led to reduction of the C=C

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• favour of the monohalide 3am (entry 1, Table 1). The reduction of the volume of the aqueous phase (Table 1, entry 2) resulted in a small shift towards the desired product 3a but also in the predominant overreaction towards tribromide 3at. Formation of 3at was substantially controlled by reducing the

• plateau around 60%. Data available in the literature suggested a beneficial effect coming from the reduction of the water amount [62]. As all the existing water originates from the employed reagents like aqueous HBr and H2O2, the combination of NaBr and H2SO4 was explored as a potential source of