Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• -(trifluoromethyl)-1-alkenes strongly interact with electron-rich zero-valent nickel species to form nickelacyclopropanes C [15][16][17]. These intermediates enable C–F bond activation through the formation of nickelacyclopentenes D with alkynes, followed by β-fluorine elimination, leading to defluorinative

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• -difunctionalization of alkenes carried out with carbazates (N-aminocarbamates) and (hetero)arene nucleophiles or amines exploiting N-(tert-butyl)-N-fluoro-3,5-bis(trifluoromethyl)benzenesulfonamide (NFBS) as intermolecular hydrogen-atom-transfer reagent results in alkylarylation processes (Scheme 5) [19]. The

• , hydrazines and alkenes with Cu(OTf)2 (20 mol %) in CH2Cl2 at reflux is a useful tool to access substituted 4,5-dihydropyrazoles 31 (Scheme 23) [40]. The products reasonably result from a Mannich/cyclization/oxidative transformation of the substrates in which Cu(OTf)2 is involved in more steps. The reaction

• multicomponent synthesis of acyclic and heteropolycyclic systems under copper(II) triflate catalysis are reported. Using alkenes and alkynes as substrates, various types of reactions were considered, including hydroamination, condensation, cross-coupling, C–H functionalization, cycloaddition, aza-Diels–Alder

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• the field, other dienes bearing two nitrogen atoms in their structure such as 1,3-azadienes or azo-alkenes are also included. On the contrary, asymmetric cyclizations involving aza-ortho-quinone intermediates and in situ-formed 1-azadienes were excluded as they have been discussed in other recent

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• ]-cycloaddition reaction between electron-poor 1,2-diaza-1,3-dienes and electron-poor alkenes in refluxing acetonitrile was reported leading to various substituted tetrahydropyridazines in 17–78% yields (Scheme 1c) [26][27]. Nevertheless, these methods are neither relevant for the synthesis of 1 nor appropriate

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

• , the intramolecular HVI-mediated halocyclisation of alkenes using carbon, oxygen, nitrogen or sulfur nucleophiles. Herein, we describe the examples reported in the literature, which are organised by the different halogens involved and the internal nucleophiles. Keywords: cyclisation; halogenation

• ; heterocycles; hypervalent iodine; oxidation; Introduction Halogenated carbocyclic and heterocyclic compounds are present in many active pharmaceutical ingredients [1][2]. The intramolecular halocyclisation of alkenes mediated by HVI(III) reagents allow access to a range of halogenated cyclic scaffolds in a

• 4 [9][10] (Figure 1). Halogenated cyclised structures have also been found to exhibit medicinal and pharmaceutical properties, including antibacterial [11], antibiotic [12], and enzyme inhibition [13] among others. The general mechanism for the HVI-mediated halocyclisation of alkenes proceeds

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• formation of peroxide 9. The enantioselective peroxidation of alkenes 10 with TBHP with the formation of the optically active products 11 was carried out in good yields and low ee by the use of in situ-generated chiral bisoxazoline–copper(I) complexes (Scheme 7) [43]. Studying the oxidation of α-pinene (12

• alkenes 41 was disclosed (Scheme 17) [59]. The target 6-trifluoromethyl peroxides 42 were synthesized in good yields under mild conditions. The electrophilic CF3 radical A, generated from CF3SO2Na through single-electron oxidation by using Mnn/TBHP system, is captured by the carbon–carbon double bond to

• –peroxidation of unsaturated alkenes 43 using AgSCF3 and TBHP was realized in the presence of the copper catalyst (Scheme 18) [60]. The radical trifluoromethylthiolation of alkenes 43 triggers a 1,5-HAT and further recombination of the generated C-centered radical with the tert-butylperoxy radical to afford the

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• , alkenes) and halogens allowing an array of post-functionalization reactions. Finally, the trifluoromethylthiolation of molecules derived from compounds of interest was achieved to illustrate the synthetic utility of the method. Hence, the desired products 2v–x were efficiently isolated. To get more

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• as heteroconjugated alkenes with difluorocarbene to give 2,2-difluoro-2,3-dihydrofurans [50] remained unsuccessful (Scheme S2 in Supporting Information File 1). Two mechanisms have been proposed for the difluoromethylation of ketones, as illustrated in Scheme 4A. In both cases, the process begins

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

• )alkenes and -phenanthrenes [78]; yet, adjacent hindrance is not a problem in this case. Clearly, more work is required on the Suzuki–Miyaura coupling of molecules with sterically demanding ‘pockets’ with opposing and adjacent hindrance. In conclusion, a library of arm-extended dodecasubstituted porphyrins

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• 350100, China 10.3762/bjoc.20.232 Abstract The catalytic (asymmetric) allylation and propargylation have been established as powerful strategies allowing access to enantioenriched α-chiral alkenes and alkynes. In this context, combining allylic and propargylic substitutions offers new opportunities to

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluorine-containing building blocks have been developed [21][22][23][24][25]. Jubault and Poisson et al. reported SN2’ reactions of hydride or alcohols to electrophilic fluorine-containing alkenes gave the corresponding fluoroalkenes (Scheme 1B) [21]. In recent years, many fluorine-containing coupling

• Sonogashira cross-coupling to exploit the unique structure of multihalogenated fluorovinyl ethers 1 for the synthesis of many kinds of fluoroalkenes 2 and fluoroenynes 3 in moderate to high yields. The synthesized alkenes 2 still possess reactive chlorine atoms and phenoxy groups. Thus, new multisubstituted

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• alkenes [10][11], they have since found applications in catalysis [12][13]. Among the first catalytic uses of FLPs were the hydrogenation of unsaturated compounds [12][14] and the reduction of CO2 using H2 as a reductant [7][15][16][17]. FLPs have become an attractive avenue for the reduction of CO2

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• derived from the interaction of non-activated alkenes with thianthrene [24]. This procedure has the advantage of separating the oxidative activation of the alkenes from the aziridination step, allowing efficient access to a variety of aziridine building blocks containing sensitive functional groups. This

• . Nucleophilic attack on the benzylic carbocation results in a 1,3-difunctionalized product (Scheme 18). The introduction of two heteroatoms was reported by Liu, Li, and Jin [27]. They developed a method demonstrating excellent tolerance for a wide range of readily available alkenes and O,N-centered nucleophiles

• ] annulation of hydroxamic acids 54 with alkenes for approaching benzo[c][1,2]oxazines [30]. This method successfully achieved the LSF of several natural products such as lithocholic acid and estrone, affording the following benzo[c][1,2]oxazine derivatives in moderate to good yields (Scheme 22). The

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• , Via Gobetti 85, 40129 Bologna, Italy 10.3762/bjoc.20.210 Abstract The direct nucleophilic addition of amides to unfunctionalized alkenes via photoredox catalysis represents a facile approach towards functionalized alkylamides. Unfortunately, the scarce nucleophilicity of amides and competitive side

• reactions limit the utility of this approach. Herein, we report an intramolecular photoredox cyclization of alkenes with β-lactams in the presence of an acridinium photocatalyst. The approach uses an intramolecular nucleophilic addition of the β-lactam nitrogen atom to the radical cation photogenerated in

• the linked alkene moiety, followed by hydrogen transfer from the hydrogen atom transfer (HAT) catalyst. This process was used to successfully prepare 2-alkylated clavam derivatives. Keywords: β-lactam; acridinium photocatalyst; alkenes; amides; intramolecular radical reaction; photoredox catalysis

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• developed an electrophilic phenylseleno trifluoromethoxylation of alkenes, which leads to β-selenylated trifluoromethoxylated compounds or, upon subsequent reduction, to the trifluoromethoxylated ones. Keywords: DNTFB; electrophilic addition; fluorine; selenium; trifluoromethoxy; Introduction Due to the

• compounds from alkenes and DDPyOCF3, more precisely to α-trifluoromethoxylated, β-phenylselenylated compounds. Results and Discussion The electrophilic addition of phenylselenyl halides to alkenes to form a selenonium intermediate that can be intercepted by an external nucleophile is a well-known method to

• obtain 1,2-disubstituted compounds [72][73][74]. Therefore, the reaction of alkenes with electrophilic sources of phenylselenyl in presence of DDPyOCF3 as a nucleophilic source of the CF3O group was studied (Table 1). First, we started from the optimal conditions previously established for the

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

• diselenide, the addition of PhSe• to alkenes proceeds 10 to 50 times slower than PhS• [29]. For this reason, the addition of (PhSe)2 to isocyanides, whether aliphatic or aromatic, rarely proceeds. The exception is the addition to p-nitrophenyl isocyanides, which does proceed, but this is because the electron

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

• ) cycloadditions with alkenes or alkynes to form pyrazoles, also in the sense of MCR. Furthermore, while not strictly classified as pericyclic reactions, hydrazones are also recognized as CN2 building blocks in pyrazole synthesis [169]. 1,3-Dipoles as key intermediates Various methods have been developed for the

• al. used this for the regioselective one-pot synthesis of pyrazoles 175 by 1,3-dipolar cycloaddition with electron-deficient alkenes (Scheme 59) [177]. The reaction is carried out in air to oxidize an intermediary

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

• agrochemical industries. The (3 + 2)-cycloaddition between nitrile imines and alkenes represents one of the most efficient strategies to prepare these azacycles. However, conventional methods for the generation of the nitrile imine involved the use of unstable hydrazonoyl halides or the oxidation of aldehyde

• -derived hydrazones under harsh reaction conditions. In 2023, the group of Waldvogel presented a formal electrooxidative (3 + 2)-cycloaddition between aldehyde-derived hydrazones 72 and alkenes 73 to yield a large range of N-arylpyrazolines 74 under mild reaction conditions (Scheme 14) [58]. A biphasic

• solvent for ethyl glyoxylate phenylhydrazone 72a while methyl tert-butyl ether was preferred for aromatic and aliphatic aldehyde-derived hydrazones 72b. Styrenes, enamines as well as electron poor aliphatic alkenes were all suitable dipolarophiles. From a mechanistic point of view, the authors proposed

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• aza-Wacker cyclizations under acidic conditions, which are expected to proceed via radical cations generated by single-electron oxidation of alkenes. Keywords: alkene; aza-Wacker cyclization; electrochemistry; radical cation; sulfonamide; Introduction Activating bench-stable substrates is the first

• different, their creative use may pave the way for complementary bond formation. This merging is unique and such intermediates could potentially take part in both radical and ionic bond formation. However, the mechanisms involved can be complicated and are not fully understood. Alkenes and styrenes are

• , differently substituted alkenes 11, 14 were prepared and subjected to the reaction under electrochemical and non-electrochemical conditions (Scheme 4). In the case of the trisubstituted alkene 11, the six-membered anti-Markovnikov product 12 was selectively obtained under electrochemical conditions, while the

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

• them group transfer reactions [21] and as building blocks [22][23][24]. The synthetic potential of NHIs has been previously studied in model transformations such as thioanisole oxygenation, oxidative lactonization, or diacetoxylation of alkenes [25][26][27][28]. In this work, we want to apply NHIs in a

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

• semihydrogenation of alkynes to form Z-alkenes using a PEM reactor [31]. The Pd/C catalyst was essential for the reaction. They recently found that a PEM reactor with a Rh/C catalyst was effective for the stereoselective reduction of cyclic ketones [40]. Nagaki et al. reported the electrochemical deuteration of

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

• intermediates in organic synthesis for the construction of all-carbon-substituted quaternary centers (Figure 1A). However, conventional methods for the synthesis of tertiary alkylnitriles such as direct functionalization of alkylnitriles [10] and hydrocyanation of alkenes [11][12][13][14] are typically hindered

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• rearrangement using benzonorbornadiene and the chiral natural compound (+)-camphene as bicyclic alkenes, selectfluor as an electrophilic fluorine source, and water and various alcohols as nucleophile sources. The structure of bicyclic oxy- and alkoxyfluorine compounds was determined by NMR and QTOF-MS analyses

• alkenes. We previously developed a dihomohalogenation method using selectfluor as an oxidant [27]. Herein, we synthesized bicyclic oxy- and alkoxyfluorine compounds using selectflour as an electrophilic fluorination reagent, water and various alcohols as an nucleophile. Results and Discussion In this

• study, benzonorbornadiene (1a) and the chiral natural product (+)-camphene (1b) were used as bicyclic alkenes. Safe, easily soluble, easy to use, stable solid, reactive and commercial available selectfluor [18][27][28] was selected for electrophilic fluorination source. Water and various alcohols were

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

• alkenes regioselectively to furnish their respective oxazoline regioisomer (Scheme 1d). Herein, we report that lithium salts such as LiBF4 or LiPF6, which are often used in lithium-ion batteries, can be used to activate hypervalent iodine catalysts to enable olefin oxyamination reactions with simple

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

• , Wang and co-workers [30] demonstrated the photomediated synthesis of γ,γ-difluoroallylic ketones by reacting trifluoromethyl alkenes and acids in the presence of PPh3 additive and iridium photocatalyst in basic medium (Scheme 3). This methodology was suitable for a wide range of carboxylic acids in the

• and is entirely redox-neutral. The authors have shown that simple cesium alkyl oxalates of tertiary alcohols can easily couple with electron-deficient alkenes in the presence of visible light. Initially, the [Ir(III)] photocatalyst is excited to the long-lived higher-energy state *[Ir(III)]. Then, the

• photocatalysis. The generated alkyl radicals then undergo the desired addition with alkyne to produce alkenyl radicals that via Ni-catalysed coupling reactions with aryl bromides form trisubstituted alkenes Z-selectively. Internal alkynes are not suitable for this transformation due to the steric reason, but