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

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• secured due to the favorable hydrogen bonding (O–H∙∙∙N) between the oxime units; this idea is supported by 1H NMR spectroscopy which shows the presence of two distinct hydroxyl proton signals. The reduction of 7d in the presence of Pd/C and hydrazine monohydrate afforded 1,10-phenanthroline-5,6-diamine

• efficient electron transport. However, compounds with LUMO levels ≈−4.0 eV are prone to undergo oxidation with O2 or reduction with H2O [35]. This could be the reason why electron transport properties in the OFETs previously reported by Yamashita are not very good [25]. Therefore, in the case of DPQD

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• . The reduction in the absolute value of χconst suggests the upshift of the Fermi energy from the Dirac point in the electronic band of nanographene in ACFs, being consistent with charge transfer from FeCp2 observed in XPS. The decrease in the absolute value of the Weiss temperature Θ from −6.4 K for

• cation spins are less than those for edge-state spins. The apparent reduction in Θ for FeCp2-ACFs-150 is attributed to the contribution of FeCp2+ spins having less exchange interaction in the observed magnetic susceptibility. So, the spin magnetism of the guest molecule is induced by host–guest

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• the presence of K2CO3 (3 equiv) as base, an isonitrile (1.2 equiv), and Pd(OAc)2 (10 mol %) which in situ undergoes a reduction to Pd(0) (Scheme 2). Another example was published by Wu's group, who carried out the synthesis of 1-(1H-indol-1-yl)-2-arylethan-1-one derivatives by promoting the formation

• reaction mechanism proceeds with an initial reduction of Pd(II) to Pd(0) followed by oxidative addition on the ArCH2–Cl bond to form the ArCH2–PdII–Cl complex. Then, insertion of CO, from TFBen, takes place followed by nucleophilic displacement and reductive elimination. The obtained compound undergoes

• the catalyst undergoes reduction, therefore, rather using only CO, a mixture of CO–air (12:48 bar) was used with the aim of oxidizing the Pd(0) species in order to restore the catalyst able to catalyze the process again. The reaction mechanism proceeds with an initial interaction between the Pd(II

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• 2.0 equiv of diisopropylethylamine (DIPEA), 2a could be obtained in quantitative 19F NMR yield although a reduction to 1.5 equiv led to a significant drop in efficiency, delivering the acyl fluoride in only 30% 19F NMR yield together with 45% of thioester 3a (Table 1, entries 4 and 5). At this stage

• the efficiency of the reaction, whereas a 19F NMR yield of only 11% was achieved in DMF (Table 1, entries 10–12). Increasing the reaction concentration to 0.2 M in DCM led to a reduction in the 19F NMR yield of 2a to 74% (Table 1, entry 13). Finally, optimisation of the reaction time revealed the

• the acyl fluoride with addition/elimination of fluoride to a thioester intermediate and independent deoxyfluorination of a second equivalent of the acid substrate by the released −SCF3 anion both operating under the reaction conditions. This allows for the reduction in the loading of BT-SCF3 to sub

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• appears to have the opposite effect, as 5m demonstrates. Although it was expected that this would result in a higher absorption intensity, a drastic reduction in the intensity was observed. The extinction coefficient of 5m (8766 M−1 cm−1) was rather low compared to 5d. Furthermore, the substitution of a π

• -donor group by a π-acceptor group led to a reduction of the absorption intensity until it almost disappeared. This behavior can be observed in the spectra of 5l. As the spectra of 5k and 5l indicate, the spectral influence of a p-substituted alkyne-linked phenyl group appears to be negligible. However

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• fluorothalidomide [8]. Similarly, the reduction in the number of aromatic groups and increase in the level of saturation have risen to prominence as a way of improving low aqueous solubility, metabolic instability, or low lipophilicity in drug candidates that contain a high number of these functionalities [9][10

• (±)-30. In a related strategy, Procter and co-workers prepared 1,2-BCHs (±)-33a–e from BCBs 32 via a SmI2-catalysed radical relay alkene insertion (Scheme 3C) [35]. This approach relied on single-electron reduction of the ketone moiety and ring-expansion from the ketyl radical anion. Electron-deficient

• alkenes including acrylates, vinyl sulfones, and acrylamides could all be incorporated and the number of accessible bifunctional 1,2-BCHs was increased further by chemical transformation (Scheme 3D) [35]. Among the reported transformations were reduction of the ketone (to (±)-34), hydrolysis of the

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• characterized. Each isolated homolog exhibited similar oligomerization and heme occupancy as Vs NnlA. Reduction of this heme was shown to be required for NnlA activity in each homolog, and each homolog degraded NNG to glyoxylate, NO2− and NH4+ in accordance with observations of Vs NnlA. It was also shown that

• reduction of which is required for NNG degradation activity. In addition, we show that NnlA cannot degrade 2-NAE. Combined with previous substrate scope studies, this result strongly suggests that NnlA is specific for NNG. The implications of our results in understanding the environmental abundance and

• stoichiometric heme occupancy (Table 1). All homologs degrade NNG to glyoxylate, NH4+, and NO2− Previous work showed that reduction of the Vs NnlA heme was required to activate NNG degradation. To test this requirement for the homologs, reduced samples of 5 μM of each NnlA homolog containing 350 μM NNG in

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• ) is produced selectively when cellulose-containing materials, including lignocellulosic biomass, are acidified and pyrolysed [1][2]. Lab scale synthesis of this chiral material can be accomplished in a single step without special glassware [3], while large scale production of the reduction product

• reduction using NaBH4 as per our previously published approach (Scheme 1) [9]. When α-alkylations are performed using 2, the second alkylation step is faster than the first, meaning that only the dialkylated products are formed [16], and the reduction is highly selective with approach of the reductant from

• stereoisomer 10f in 91% yield. The selectivity of the NaBH4 reduction was confirmed for both 10d (see discussion in Supporting Information File 1) and 10e by X-ray crystallography (Figure 2 and Scheme 1, respectively). The oxygen-migration reaction giving 11a was initially observed using the readily available

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• more efficient reactions with alkene 88 (Table 6). In 2022, Oestreich reported the in situ formation of HCl by Lewis acid-induced Grob fragmentation of acid chloride 92 (Scheme 15B) [68]. The inconvenience of this method is that 92 has to be prepared in two steps, including a Birch reduction (Scheme

• state thereof, denoted with an asterisk, possessing a reduction potential of 2.0 V versus SCE (saturated calomel electrode). Subsequently, this excited state undergoes quenching through photoinduced electron transfer (PET) with styrene 5. The resulting vinyl radical cation exhibits electrophilicity at