Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• was proposed by conducting the reaction in the presence of TEMPO (Scheme 7). The electron-deficient and sterically encumbered diaminophosphine oxide could also produce the corresponding products in this method. Gas chromatography analysis confirmed that molecular hydrogen was the only byproduct of

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

• -trifluoromethylalkenes 38 with hydrosilanes and allylic chlorides 40 (Scheme 14b) [55]. In their work, a chiral α-CF3 alkylcopper intermediate 39 was formed through the regio- and enantioselective hydrocupration of electron-deficient alkenes 38 with an in situ-generated CuH species. Subsequent electrophilic trapping of

• showed a broad scope, tolerating both 1,1-diborylalkanes with N-tosyl-protected amines and TBS-protected alcohols, as well as substrates containing alkenes and alkynes. Various allylic bromides 46 with electron-rich and electron-deficient aryl substituents worked well, giving homoallylic boronic esters

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

• thus to have a better control of the selectivity and the DAR, leading to more homogeneous ADCs. In this specific context, photocatalysis (Figure 2) enables site-specific bioconjugation by generating reactive intermediates (such as radicals or electron-deficient species) that can selectively react under

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• -workers developed chiral amine 1 with an electron-deficient iodine atom, which catalyzed the Mannich reaction in excellent yields and enantioselectivities [17]. In 2020, Huber and co-workers reported the bis(iodoimidazolium) 2-catalyzed Mukaiyama–aldol reaction of carbonyl compounds with enol silyl ethers

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

• derivatives containing electron-deficient groups (like 4, 10, 12, 14 and 23) show slightly but not significantly higher Z→E conversion rates than the other coupling products presented in this work. The nitrogen-substituted derivatives 19–21 show significantly lower conversion rates of 41–61%. This behavior

• pH 7.4 compared to 41% in acetonitrile, while in acidic aqueous media a PSS of 62% E for the Z→E photoisomerization was observed. This is due to the complete protonation of the amino group converting it to an electron-deficient substituent. The thermal half-lives of 13 and 21 increase by a factor of

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

• optimized reaction conditions in hand, next, the substrate scope was evaluated (Scheme 2). Symmetrical biaryls with electron-deficient substituents such as Cl (4b) or CF3 (4c) afforded the respective Br(III) products 1b,c in slightly reduced yields as compared to that of 1a. Gratifyingly, electron-rich MeO

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

• as the participating group facilitating the formation of a 1,2-trans glycoside (Scheme 2). In general, the cleavage of the activated anomeric leaving group of the glycosyl donor 9 leads to the formation of an electron-deficient oxocarbenium ion 10. The participating vicinal acyl group interacts with

• the anomeric carbon forming an electron-deficient bicyclic acyloxonium ion intermediate 11 which blocks the α-face of the glycosyl ring, inducing the attack of the nucleophilic acceptor 12 to approach from the opposite face to form the 1,2-trans glycoside 13 primarily. Various protecting groups for

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

• study found that by using [Os(phen)3]2+ as the photocatalyst and 660 nm red light, the reaction exhibited greater functional group tolerance, handling a variety of electron-deficient, neutral and rich (hetero)aryl bromides 9 and primary and secondary amine-based nucleophiles 10 with minimal degradation

• sacrificial reducing agents (Scheme 6), contrasting with traditional blue-light photocatalysis which led to substrate decomposition [33][34]. The axial ligands on the ruthenium phthalocyanin complex, particularly electron-deficient pyridyl groups, were found to influence the catalytic activity by stabilizing

• the substrate, an activated ester 25, subsequently generating carbon-centered radicals without the need for sacrificial electron donors via a decarboxylation process. In reacting with electron-deficient alkenes or alkynes 26, these radicals further yield tetralin and dialin moieties 27, respectively

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• (12) is generally a stronger activator than heteroaryl (1a–6a) or electron-deficient aryl groups (13). In contrast, pyridinium and benzimidazolium (1b–5b) systems show substantially higher capacities to enhance the HB donation ability of the CF2H group, underscoring the distinct nature of these

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• adopted a nonplanar conformation, with one aromatic residue protruding out of the macrocyclic skeleton plane. Adopting such a conformation rendered it possible for the π-electron-rich phenyl ring to interact strongly with π-electron-deficient guest molecules G1 by means of charge–transfer interactions and

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• loading, providing an alternative strategy for 1,2-diamine synthesis (Figure 16) [71]. This reaction successfully expanded the substrate scope from electron-rich to electron-deficient alkenes, which were considered challenging substrates in previous diazidation reactions. A possible mechanism is proposed

• systems combining copper catalysis with electrocatalysis have been developed to avoid the use of chemical oxidants. Thus, the substrate scope was expanded to include electron-deficient arylboronic acids. In 2019, Gale-Day et al. developed electrocatalytic Chan–Lam couplings of arylboronic acids with

• primary anilines using a copper catalyst and dual Cu-electrode system to form C–N bonds (Figure 19) [79]. This catalytic system demonstrates a broad substrate scope, including electron-deficient boronic acids, which are typically regarded as challenging substrates because of their low reactivity in Chan

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

• are generated by treating 1,1-difluoroethylenes with a zirconocene equivalent (ZrCp2, Scheme 1a) [8]. The resulting 1-fluorovinylzirconocenes B then undergo palladium-catalyzed coupling with aryl iodides to produce arylated fluoroethylenes. Additionally, (ii) we observed that electron-deficient 2

• coupling between these components (Scheme 1b). Among aromatic fluorides, we have targeted 2-fluorobenzofurans 1 for C–F bond activation [19]. These compounds, which we prepared efficiently via 5-endo-trig cyclization of β,β-difluoro-o-hydroxystyrenes [20][21], possess a C–C double bond with an electron

• -deficient carbon atom owing to the nearby fluorine and oxygen atoms. We expected that 2-fluorobenzofurans 1 could form nickelacyclopropanes E upon treatment with zero-valent nickel species. Subsequent β-fluorine elimination from these intermediates E would facilitate the activation of aromatic C–F bonds

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• axially chiral N-aryl succinimides 54. The tentative mechanism comprises the formation of the Breslow intermediate Int-31 from the catalyst carbene and aldehyde 52, which then adds to the electron-deficient double bond of maleimide giving rise to Int-32 (Scheme 17). Chi and co-workers developed an

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available

• ; Introduction The construction of C(sp3)–C(sp3) bonds is a highly important target in synthetic organic chemistry. Historically, polar conjugate additions have been a benchmark method for constructing these bonds by functionalizing an electron-deficient olefin [1][2][3]. Recently, however, radical-based

• pathway for the functionalization of an electron-deficient olefin is the Giese reaction (Figure 1) [6][7]. This reaction involves the hydroalkylation of the olefin via radical addition (RA), followed by either hydrogen-atom transfer (HAT) or single-electron transfer (SET) and protonation. Traditionally

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

• -workers reported a cinchona alkaloid-derived thiourea-catalyzed regio- and stereoselective cycloaddition of 3-isothiocyanatooxindoles and imines containing two or three electron-deficient unsaturated bonds [25]. Firstly, the (3 + 2) cycloaddition of 3-isothiocyanatooxindoles 4 and aldimines 5 was explored

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

• , and either sodium hydroxide or sodium hydrogen sulfide to obtain a cyclic imine. Subsequently, the U-3CR is performed, where the cyclic imine reacts with an electron-deficient 2-fluorobenzoic acid and an isocyanide to yield a bisamide. Then, the bisamide undergoes an intramolecular SNAr reaction to

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• summarized. In 2014, Kadish and co-workers reported a series of planar and nonplanar metal-free tetraarylporphyrins, indicating the potential of these macrocycles for the generation of molecular hydrogen under acidic conditions [110]. Four years later, Villagrán and co-workers used electron-deficient metal

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• catalyst tolerated all p-, m-, o-Cl-substituted benzaldehydes in terms of both reactivity and selectivity, affording the essentially same results as benzaldehyde (2b–d). Other electron-deficient substituents CF3 (2e) and Br (2f) did not adversely affect the reaction. However, electron-donating substituents

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 214 (Scheme 67) [136]. Initially, I− promotes the decomposition of TBHP to generate the tert-butyloxy radical and the tert-butylperoxy radical A. The tert-butylperoxy radical A adds preferentially to the electron-deficient alkene 214 to give the electrophilic radical B, which undergoes iodination

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

• Sondos A. J. Almahmoud,
• Joseph Cameron,
• Dylan Wilkinson,
• Michele Cariello,
• Claire Wilson,
• Alan A. Wiles,
• Peter J. Skabara and
• Graeme Cooke

Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244

• dicyanomethylene-functionalised violanthrone derivatives (3a, 3b and 3c) featuring different alkyl substituents. It is found that the introduction of the electron-deficient dicyanomethylene groups significantly improves the optical absorption compared to their previously reported precursors 2a–c. All compounds are

• that molecular tailoring of violanthrone is simple and feasible. We have synthesised three soluble violanthrone derivatives with different side chains and found that due to the introduction of the electron-deficient dicyanomethylene groups, along with the extended π-conjugated framework, all compounds

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

• Cs2CO3 as shown in Scheme 1. The substrate scope exhibits that on using electron-deficient diaryliodonium salts as an arylating agent, α-fluoroacetamides 8 were obtained in moderate to good yields through a spontaneous arylation/deacylation cascade. The deacylation reaction is considered due to the

• presence of fluorine and a newly installed electron-deficient aryl group on α-carbon which increases electrophilicity of the α-carbon center [55]. The proposed reaction mechanism (Scheme 2) begins with the formation of one of two potential iodine intermediates, labeled as I or II. These intermediates arise

• reactions leads to the formation of the desired arylated α-aryl-α-fluoroacetoacetamides 7. The tetrasubstituted fluorocarbon center becomes more electrophilic in the presence of an electron-deficient aryl (Ar) group. This increased electrophilicity facilitates a base-mediated deacylation reaction, resulting

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• coefficients and bathochromically shifted absorption bands which might be a result of a certain intramolecular charge transfer between the donating N,N-dimethylamino group and the electron-deficient uracil moiety. Similar effects are observed for the emission spectra. The emission maxima of N,N-dimethylamino

Photoluminescence color-tuning with polymer-dispersed fluorescent films containing two fluorinated diphenylacetylene-type fluorophores

• Kazuki Kobayashi,
• Shigeyuki Yamada,
• Motohiro Yasui and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2682–2690, doi:10.3762/bjoc.20.225

• short-axis direction of the electron-deficient aromatic ring significantly retards the internal conversion via the formation of H···F hydrogen bonds, leading to a marked blue fluorescence in the crystalline state (Figure 1b) [17][18][19][20]. Recently, the introduction of N,N-disubstituted amino groups

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• . Moreover, the N-aryl-substituted TATA+ cations have been used as the building units of porous organic polymers for capturing CO2 [27]. Cations with characteristic electron-deficient planar triangular geometries were used as scaffolds for various supramolecular cage structures [28][29]. Although

• electron-deficient TATA+ core through the interactions of the methyl units. In fact, in 2+-Cl−, Cl− was located 3.43 Å above the TATA+ core and was interacted with the surrounding CH3 units, with C(–H)···Cl− distances of 3.74, 3.85, and 3.96 Å (Figure 3a, Figure 5a and Figure S17 in Supporting Information

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

• C–H hydroxylation process by combining continuous flow chemistry and electrochemistry (Scheme 8) [16]. The surface modification of electrodes can lead to improved reactivity and selectivity. In this regard, Li and coworkers developed electron-deficient W2C nanocrystal-based electrodes to enhance the

• 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