Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• investigation into whether such moderate activation strategies could facilitate copper-mediated coupling reactions of sterically demanding alkylboronic esters under mild conditions. After thorough reaction optimization, t-BuLi emerged as the superior activating agent, outperforming other organolithium compounds

• allylic substitution reactions Among the various approaches in copper-catalyzed asymmetric allylic substitution, copper hydride (CuH) catalysis has received significant attention due to its unique ability to generate configurationally well-defined chiral organocopper species 28 under mild conditions

• -substituted terminal alkynes 42, including the industrially relevant acetylene and propyne. Interestingly, switching to the ligand (S,S)-Ph-BPE (L1) resulted in the asymmetric 1,2-difunctionalization of aryl-substituted terminal alkynes 42. The high levels of regio- and stereoselectivity achieved under mild

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• emerged as a transformative approach in the modification of proteins, enabling researchers to achieve selective and efficient conjugation under mild conditions [37]. By utilizing visible light and transition-metal catalysts, this technique allows the generation of reactive intermediates that can

• proteins and antibodies, enabling selective covalent bond formation and functionalization under mild conditions. However, its use in biomolecule modification comes with several specific features that require consideration. Some of these are detailed below. Photoaggregation: The possibility of photoinduced

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• reaction [71]. Here, the reaction is carried out under mild conditions (CH2Cl2, 70 °C) without the need for catalysis or additional base for the activation of C–H and C–X bonds of the alkyne and dihalomethane compounds, respectively. However, this strategy has a limited scope in terms of the alkyne

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• cross-coupling reactions were performed by an organic halide reacting with an organotin compound. A great advantage of the used organostannanes is the easy accessibility, and their high air and moisture stability, so that usually a wide range of functional groups can be introduced under mild conditions

• -acetyl diazocine 22 under the conditions described by Hugenbusch et al. [37] showed no product formation and only starting material was isolated (Scheme 2). The palladium-catalyzed introduction of cyano groups under mild conditions in analogy to Iqbal et al. [38] gave the cyano-substituted N-acetyl

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• diaryl λ3-bromanes under remarkably mild conditions with subsequent applications of the in situ-generated arynes in cycloaddition reactions [3], meta-selective reactions with oxygen and nitrogen nucleophiles [4][5], regiodivergent meta or ortho-alkynylations [6], and regioselective (di)halogenation [7

• oxidation of 2,2'-dibromo-[1,1'-biphenyl] into mono-λ3-bromane 5 would set the stage for the key cyclization event (Scheme 1, reaction 2). We also reasoned that an anodic oxidation of the aryl bromide is perfectly suited for the generation of mono-λ3-bromane 5 under mild conditions [16][17][18]. This

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• -1,3-dimethylimidazolinium hexafluorophosphate (ADMP) in the presence of DBU in acetonitrile. This one-pot process enables sequential diazotization and cyclization, leading to the formation of two or three C–N bonds under extremely mild conditions, with excellent tolerance for various functional groups

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• sections. Similarly, Pertel and co-workers also demonstrated the use of 2-(2,2,2-trichloroethoxy)-2-oxazoline glycosyl donor 22 (Scheme 4) which could be used for stereo- and regioselective glycosylations using extremely mild conditions [94] and requiring low concentrations of the catalyst. In this case

• . Thus, Vatèle devised a temporary protecting group named 2-(prenyloxymethyl)benzoyl (POMB, 43) which could be selectively deprotected under mild conditions by a combination of DDQ/Yb(OTf)3 keeping the other protecting groups, like acetyl, chloroacetyl, benzoyl, pivaloyl intact [125]. Owing to its ester

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• become a powerful approach for achieving sustainable chemical transformations, combining high efficiency with energy-saving, mild conditions. By harnessing the deeper penetration and selectivity of red and near-infrared light, this method minimizes the side reactions typical of higher-energy sources

• properties beyond 645 nm, providing access to low-energy red-light-driven chemical transformations. The catalysts have successfully facilitated the dehalogenation of 18 different α-halo ketones 33 with minimal catalyst loading (0.1 mol %) and high yields under mild conditions. For instance, bromoacetophenone

• highly effective platform for improving reaction efficiencies. These molecules can facilitate single-electron transfer or energy transfer under mild conditions, and their structural diversity allows for fine-tuning of their redox potentials and light absorption characteristics. This adaptability makes

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

• successfully synthesize a range of 2-arylbenzofurans with various substituents. The reaction, which proceeded under mild conditions, involved β-fluorine elimination from nickelacyclopropanes formed by the interaction of 2-fluorobenzofurans with zero-valent nickel species. This protocol facilitates orthogonal

• developed efficient metal-mediated methods for activating (i) vinylic [8][9][10][11][12][13] and (ii) allylic C–F bonds [14][15][16][17][18] using β-fluorine elimination under mild conditions. In these studies, (i) we discovered zirconium-mediated β-fluorine elimination from zirconacyclopropanes A, which

• ]benzofuran (3fa) in 81% yield. Next, we explored the mechanism of the coupling reactions between 2-fluorobenzofurans 1 and arylboronic acids 2. Because these reactions proceed under mild conditions despite involving aromatic C–F bond activation [19], direct oxidative addition of C–F bonds is unlikely (Scheme

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

• demonstrated high tolerance to functional groups and runs, under mild conditions, with electron-poor diazo derivatives such as 2-diazoacetate, 2-diazoacetonitrile, 2-diazo-1,1,1-trifluoromethane, diazoamide, and diazophosphonate. Condensation of 2-naphthol, aromatic aldehydes and acyclic 1,3-dicarbonyl

• cascade reaction for the preparation of α-alkoxy-N-alkyltriazoles 44 that was developed starting from aliphatic aldehydes, alcohols, TMSN3 as azide source and alkynes (Scheme 33) [52]. The reaction occurs under mild conditions in acetonitrile at room temperature but is inhibited when using aromatic

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• substituted β-nitrostyrenes. This one-pot procedure allows the quick isolation of substituted β-nitrostyrene scaffolds with 62–83% yield under mild conditions, without the need for special precautions, inert atmosphere, and time-consuming purification techniques. Keywords: 2C-X; CuCl2; NaBH4; β-nitrostyrene

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• easily available 2,2,2-trifluoroethyl(mesityl)iodonium triflate reagent enabled the straightforward trifluoroethylation of diverse sulfoxonium ylides under mild conditions and short reaction times. Various computational strategies were also employed to differentiate between competing halogen bond

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

• years, the Ugi reaction has emerged as a highly considered reaction due to its mild conditions, broad applications, and product diversity. It enables the selective assembly of precursors, facilitating various post-reaction transformations such as deprotection cyclization, 1,3-dipolar cycloaddition, and

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

• of fluorine and additive, respectively. Racemic β-fluorinated piperidines 6 were synthesised in excellent yields, under mild conditions. A small amount of amino carboxylation side-product was determined to have been additionally produced from the reaction. A range of other alkenes were cyclised in

• under mild conditions in DCM at room temperature. A range of substituents on the aromatic ring were tested with electron-withdrawing groups resulting in lower yields compared to electron-donating groups. The proposed mechanism for the reaction involved formation of a chloronium ion and nucleophilic

• as the bromine source and Bu4NBr as a reaction promoter, racemic brominated pyrrolidines 54 were synthesised from a range of homoallylic sulfonamides 53 in excellent yields under mild conditions at room temperature. A mechanism was suggested by the authors (Scheme 29), whereby ligand exchange on PhI

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• . Keywords: cyclodextrin; defined structure; precise synthesis; rotaxanes; stimuli-responsive material; Introduction Stimuli-responsive materials can satisfy the existing high demands on such materials owing to their multiple functionalities (e.g., for effective energy storage or as decomposables under mild

• conditions) that facilitate sustainability [1][2][3][4][5][6][7][8][9][10]. In this regard, the rotaxane framework represents an attractive motif for implementing substantial property changes triggered by certain stimuli owing to its higher dynamic nature than those of conventional materials [11][12][13][14

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

• 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

• mild conditions with high yields of β-peroxynitroalkanes 183. The decomposition of t-BuONO produces the NO2 radical, which adds to alkene 182 to give the C-centered radical B. The tert-butylperoxy radical A or its complex Mn(III)OO-t-Bu reacts with radical B to yield the target product 183. The same

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

• reactions occurred under mild conditions and without any need of transition-metal catalysts. In 2023, Wu and colleagues successfully synthesized a range of meta-substituted biaryl ethers. The reaction involves phenols 61 and cyclic diaryliodonium salts 73, dissolved in tert-butyl alcohol, in the presence of

• group of the iodonium salt was also investigated. A potential radical-mediated mechanism was evaluated. Under mild conditions, a base-promoted arylation of general sulfinates 86 without the need for transition metals was introduced using diaryliodonium salts 16 as an aryl source (Scheme 35). Inspired by

• 101 for the S-arylation of potassium O-alkyl xanthates 100 offers a simpler approach [95]. This method operates under mild conditions, facilitating the creation of substituted S-aryl xanthates 102 (Scheme 41). Utilizing diaryliodonium salts for the arylation of xanthate anions provides a pathway for

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

• transformed into a series of useful molecules, enabling them an important backbone in organic synthesis. Lin et al. [66] used sodium sulfinates as the nucleophiles to realize the asymmetric sulfonylation of yne-allylic esters. The reaction can be carried out under mild conditions with good to excellent regio

• spiroannulation of 2-naphthols or electron-enriched phenols under mild conditions with excellent regioselectivities, enantioselectivities and diastereoselectivities (Scheme 44, 43a–g, 44a–q). In addition, the nucleophilic substitution–dearomative cyclization process between indoles and yne-allylic esters can also

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• aromatic substitution giving the final spiro-indolenine. The scope of the process has been investigated with respect to all three components. Simple operations, mild conditions, and good yields make this strategy a convenient and sustainable way to obtain novel spiro-indolenine derivatives. Keywords

• spiro-heterocyclic indolenines from readily available starting materials under mild conditions and in a diversity-oriented fashion remains desirable. In this contest, oxidative isocyanide-based multicomponent reactions (oxidative IMCRs) can be considered as a convenient tool [15]. Actually, the use of

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• , Trombay, Mumbai-400085, India Homi Bhabha National Institute, Anushaktinagar, Mumbai, PIN-400094, India 10.3762/bjoc.20.223 Abstract A transition-metal-free decarbonylation–oxidation protocol for the conversion of 3-arylbenzofuran-2(3H)-ones to 2-hydroxybenzophenones under mild conditions has been

• to scale-up due to their violent reactions at elevated temperatures. Our protocol involved mild conditions, and to our expectations, a gram-scale conversion of 3ba to 4ba proceeded smoothly without appreciable loss in the reaction yield (Scheme 3). The reduced reaction time and a lower reaction

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

•  1c). This method could be carried out without any special apparatus, and the mild conditions led to the wide range of applications. Results and Discussion Initially, we used triphenylbismuthine (1a) and bis(pinacolato)diboron (2) as the model substrates to optimize the reaction conditions (Table 1

• air under mild conditions. Therefore, many triarylbismuthines could be used to form a variety of useful arylboronates in moderate to good yields with excellent product selectivity. We hope that this new approach to the generation of aryl radicals from triarylbismuthines will lead to an increased use

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

• direct activation of C(sp3)–H bonds under mild conditions [17]. The pronounced electron-deficient W2C nanocatalysts greatly facilitate the direct deprotonation process, ensuring the longevity of the electrode by overcoming self-oxidation. The LSF of drug molecules such as ibuprofen methyl ester and

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• a carboxy group using carbon dioxide as carboxy source is generally difficult under neutral and mild conditions without the use of metal catalysts and/or ligands. This protocol represents a novel method for synthesizing diarylacetic acids 2 from the corresponding alcohols 1 in one step by using an

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• proved ineffective in facilitating the Michael addition of bisthiomalonates to conjugated ketones, whereas DABCO enabled the formation of desired products under mild conditions [30]. However, reports of highly stereoselective protocols utilizing hydrogen bonding catalysis have mainly focused on

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• ], and crosslinked polymers [14][15][16][17]. Since crosslinking polymers requires high reaction efficiency under mild conditions, developing such reactions is crucial. We previously reported the regioselective double azide addition to octadehydrodibenzo[12]annulene with hexyloxy substituents (DBA-OHex

• -withdrawing groups was successfully synthesized. This molecule underwent SpAAC with two equivalents of benzyl azide under mild conditions to quantitatively form the regioselective symmetric bistriazole product. The electron-withdrawing substituents facilitated the reaction progress as compared to the