Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• this methodology. As summarized in Scheme 2, we initially investigated the scope and effect of arylamine functionalities on this transformation. Under optimized reaction conditions, arylamines bearing either electron-rich or electron-deficient substituents at the para-position demonstrated good

• consistently high combined yields, ranging from 92% to 95%. Probably due to steric hindrance, when the phenyl group was attached to the para-position of the aniline (1e), the corresponding products 3e along with 3e′ could be obtained in 75% yields. Electron-deficient groups at the para-position, such as -Cl

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• -dimethylaminopyridine), affording (1S,2S)-N1,N2-bis((1R,2R)-2-(sulfonamido)-1,2-diphenylethyl)cyclohexane-1,2-dicarboxamides 4 in 32–87% yields. Electron-deficient sulfonamides 2a, 2e and 2f with both electron-donating methyl and strong electron-withdrawing trifluoromethyl and 4-nitrophenyl groups showed low reactivity

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• -step synthesis, convenient modification that can be achieved by introducing functional groups, electron rich and hydrophobic cavities that can effectively recognize electron deficient or neutral guest molecules, and high selectivity in binding with the guest. Their applications are extensive in the

• macrocycles such as crown ethers [43], cyclodextrins, and cucurbiturils, CAs and PAs have unique advantages. Their synthesis is simple (one-step completion), and they have adjustable conformations and π-electron-rich cavities [44][45], enabling efficient recognition of electron-deficient or neutral guest

• environment, which significantly enhances the density of π-electrons. This structural feature makes pillar[n]arenes particularly effective at encapsulating guest molecules that are either electron-deficient or neutral. For example, pillar[5]arene (PA5) has a strong binding affinity for neutral guest molecules

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• methoxymethyl group cleavage, O-to-N rearrangement, and isomerization of the double bond. An oxazoline ring formation in the resulting unsaturated amides provided the corresponding enantioenriched vinyloxazoline. The reactivity of the electron-deficient double bond in the vinyloxazoline was explored in several

• chiral HPLC. This confirmed that no erosion of enantiomeric purity had happened during the deprotection stage. With the enantioenriched vinyloxazoline S-6 in hand, we explored the reaction scope involving its electron-deficient double bond. Unfortunately, the olefin appeared unreactive or gave a mixture

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• -bromochromones via a Michael reaction of an amine with an electron-deficient alkene moiety and subsequent photocatalyzed debromination. With this dual catalytic system, a range of structurally diverse enaminone derivatives have been achieved in good yields with total trans selectivity. Mechanistic studies

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• , N=S=O, etc. dipolarophiles) [5][6][7][8][9][10] (Scheme 1, upper part). Notably, [3 + 2]-cycloadditions of the sterically crowded thiocarbonyl S-methanide 1b with electron deficient, tetrasubstituted ethylenes activated with CN and CF3 (or CN and CO2Me) groups were encountered as the first examples

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• reaction yields allowed us to establish the dependency from the electronic effects of substituents in the diaryliodonium salts. Diaryliodonium salts containing electron-deficient aryls afforded products 2 in higher yields compared to those bearing electron-donating groups (EDG). Specifically, the reaction

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• structures, enhance solubility, and expand functional diversity [6]. Substituting carbon atoms with electron-deficient nitrogen atoms introduces new opportunities to fine-tune redox potentials, charge-transport behavior, and intermolecular interactions [7]. These modifications have proven especially valuable

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• increase of the electron density on the nitrogen atom of the iodonium salt 2 when the tosyl group is replaced by a less electron-deficient mesyl group. Using optimal reaction conditions (method A), twenty seven 2,3-dihydro-N-sulfonyl-1,2-thiazoles were synthesized in 69‒96% yields. We scaled the reaction

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• ] dimerisation, this methodology enables performing photocycloadditions between electron-deficient alkenes and aliphatic ketones which had been usually avoided. One year later, Yoon and co-workers published the first highly enantioselective Paternò–Büchi reaction between quinolones 84 and ketoesters 85 (Scheme

• . published a light-induced cross-selective [2 + 2] cycloaddition between 3-(arylmethylidene)oxetanes 159 and electron-deficient alkenes 160 (Scheme 40) [91]. The methodology used a commercially available iridium-based photosensitiser and blue-light irradiation at a slightly elevated temperature. The

• from the photoexcited Ir complex, Giese-type addition of the resulting triplet diradical 164 to the electron-deficient alkene, intersystem crossing generating a singlet diradical 166 and intramolecular radical recombination. In 2022, Bull and colleagues disclosed an unprecedented synthesis of 3-aryl-3

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• various fields of organic synthesis methodology. Despite significant research achievements of amidyl radicals in the photocatalytic transformation of C(sp³)–H, C(sp²)–H, S–H, Ge–H, and B–H bonds, they still face considerable challenges in the application of hydrogen abstraction from electron-deficient C–H

• modifications of amidyl radicals aimed at optimizing their polarity via electronic effects, which may enhance their effectiveness in hydrogen abstraction from electron-deficient substrates. Additionally, strategies to optimize steric effects could improve their regioselectivity in hydrogen abstraction from

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• oxidation of azulene units is particularly efficient when performed in an electron-deficient system, as demonstrated by Tani and co-workers [71] in their synthesis of azulene-fused tetracene diimide 107 from precursor 106 (Scheme 15). Oxidation with DDQ gave the target product in very high yield (95

• 660 nm. Würthner and co-workers developed a cascade [3 + 3] annulation strategy, where Suzuki cross-coupling is followed by C–H arylation, and applied it to various electron-deficient nanographenes [81][82][83][84]. This strategy can also be applied to non-alternant PAHs. For example, azulene 127

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• methoxy (-OMe) and halogens (-F, -Cl, -Br), as well as electron-withdrawing functionalities like trifluoromethyl (-CF₃) and ester groups (-CO₂Me). However, highly electron-deficient substrates, such as those bearing cyano (-CN) or nitro (-NO₂) groups, did not react. Additionally, the study explored

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• the dienophile presents a negative charge (−0.280 to −0.325, 6a), (−0.280 to −0.327, 6h) and (−0.280 to −0.327, 6r), respectively. This structure induces electrostatic repulsion instead of the requisite attraction for a successful interaction between the electron-rich diene and the electron-deficient

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• the assembly of HIM is attributed to the weak, yet additive, secondary bonding interactions between electron-deficient iodine atoms and electron-rich oxygen atoms. These examples highlight new possibilities in materials science owing to their unique assembly via secondary bonding as well as their

• -deficient in nature owing to the presence of three electron-deficient iodine atoms within the macrocycle's framework. To better understand the electrophilic environment of the macrocyclic cavity, we have calculated the Mulliken charges on each atom of Phe HIM 1. To analyze the resultant charge of the

• cavity is highlighted by blue color in the chemical structure of phenylalanine HIM as shown in Figure 3 (left) (more figures are provided in Supporting Information File 1). Despite the core's composition of six electron-rich oxygen atoms, we hypothesized that the bowl-like macrocyclic cavity is electron

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• desired products 3bc, 3bd, 3bi, and 3bk in relatively low yields and enantioselectivities. The strongly electron-deficient 4-nitrobenzaldehyde (2l) showed the highest enantioselectivity, affording the desired product 3bl in 63% yield and >99% ee. Polycyclic fused naphthalene-1-carbaldehyde (2m) and

• . Furthermore, other diethyl 2-phenylaziridine-2,2-dicarboxylates 1c and 1d with different 1-arenesulfonyl groups were attempted, giving rise to the corresponding products 3ca and 3da in 87% yield with 88% ee and in 82% yield with 20% ee. The results indicate that aziridine 1d with an electron-deficient 1-(4

• of the catalyst for the next catalytic cycle. The electron-deficient aromatic aldehydes exhibit excellent stereoselectivity due to the π-stacking interaction between their aryl group and the electron-rich malonate group. Similar π-stacking interaction-controlled stereoselectivities were observed in

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

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

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• shift, while the emission band of 4j was slightly red-shifted. The N,N-dimethylaminophenyl-substituted compounds 4k and 4l showed the strongest bathochromic shifts of the emission spectra, which might be due to the occurrence of donor–acceptor interactions between the electron-deficient uracil and the

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• , oxidative addition of the C–I bond to palladium formed the four-membered aryl–palladium complex Int-5. Steric hindrance from the bulky dppm ligand, combined with slower aryne release (using KF as the fluoride source), attenuated aryne coordination. Under these electron-deficient conditions, CO

• in steering catalytic selectivity. In 2016, the Jiang group achieved regioselective control in the gold-catalyzed intramolecular hydroarylation of alkynes by modulating the electronic and steric effects of ligands (Scheme 2) [20]. Mechanistically, the electron-deficient phosphite ligand L1 and the

• Friedel–Crafts-type addition and protonation to complete ortho-position cyclization. In contrast, para-position cyclization was exclusively achieved through π–π interactions between the electron-rich X-phos ligand and the substrate, compensating for the electron-deficient nature of the aromatic system and

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• , we report the design of ultracycles constructed from functional tetraoxacalix[2]arene[2]triazine submacrocycles. These submacrocycles feature hydroxy groups as hydrogen-bonding (HB) donors on the lower rim, which, in combination with electron-deficient triazines, create cooperative HB and anion–π

• ultracycles in hand, we investigated the binding between the [2 + 2] ultracycle B4aH, which contains two electron-deficient cavities, and a series of dicarboxylate anions (C22−–C82− as tetrabutylammonium salts) by 1H NMR titration experiments (Figure 2). Taking C62− as an example, when it was added dropwise

• dicarboxylate C72− is included within the cavity of B4aH. The two subcavities interact synergistically with the included dicarboxylate; the two terminal carboxylate groups are respectively positioned within electron-deficient cavities of the submacrocycles, forming hydrogen bonds (2.49–2.59 Å) with the two

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