Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• ]. Hydroamination simultaneously forms C–N and C–H bonds from simple and readily available starting materials without prefunctionalization. When applied to electron-deficient alkenes such as α,β-unsaturated carbonyl compounds, nitroalkenes, or vinyl sulfones, this transformation is often categorized as an aza

• selective hydroamination chemistry. Review Copper-catalyzed aza-Michael addition Early studies on copper–amido complexes by Gunnoe The aza-Michael addition of (hetero)aromatic amines to electron-deficient olefins provides a straightforward and atom-economical route to β-amino carbonyl, β-amino sulfone, and

• nucleophilicity, facilitating conjugate addition to electron-deficient alkenes. The formation of such well-defined copper–amido complexes provides valuable mechanistic insights into copper-catalyzed hydroamination and conjugate addition reactions. Pioneering studies by Gunnoe et al. describe the synthesis and

Diastereodivergent electrophilic trapping of α-boryl lithium derivatives

• Tereza Pavlíčková,
• Noam Orbach and
• Ilan Marek

Beilstein J. Org. Chem. 2026, 22, 882–887, doi:10.3762/bjoc.22.68

• ; Introduction α-Boryl carbanions 1 (Scheme 1), also referred to as boron alkylidenes or borata alkenes, represent a fascinating class of organoboron intermediates characterized by the delocalization of electron density from the negatively charged carbon center toward the electron-deficient boron atom. This

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• with ketones resulted in unique di(pyridin-2-yl)methylene)-9H-diazafluorenes being electron-deficient ligands and functional materials. Keywords: acidic conditions; diazafluorene; diazafluorenylidene; Knoevenagel condensation; protonation; Introduction Diazafluorenylidene derivatives were reported to

• (pyridin-2-yl)methylene)-9H-diazafluorenes were obtained by condensation of 4,5- and 1,8-diazafluorenes with di(pyrid-2-yl)ketone highlighting the high synthetic potential of the Knoevenagel reaction on the way toward novel electron-deficient ligands and functional materials. Experimental General 4,5

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• )benzylamine (92) as an azomethine ylide precursor in (3 + 2)-dipolar cycloaddition reactions with electron-deficient exo-cyclic 93 and endo-cyclic alkenes 94 (Scheme 36) [77][78][79]. To generate the azomethine ylide from reagent 92, TFA in methylene chloride at room temperature or LiF in acetonitrile with

• synthesis of trisubstituted pyrrolizidines 106 via 1,3-dipolar cycloaddition reactions using proline (103), arylaldehydes 104, and electron-deficient dipolarophiles, chalcones 105 (Scheme 38). The authors suggest that the interaction of proline and arylaldehydes results in the formation in situ of an S

• electron-deficient central multiple bond of triarylidene acetylacetone. The cleavage of the cinnamoyl group that occurs during the formation of spiroheterocycles was additionally confirmed using mass spectrometry [103]. In [104][105], our group investigated three-component one-pot reactions of substituted

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• that CF3· behaves as an electrophilic radical [31][32], it was expected to react preferentially with electron-rich substrates compared to electron-neutral or electron-deficient ones. To probe this trend, trifluoromethylation was examined with substrates bearing donor substituents (methoxyarenes) and

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• (I). Indeed, the Friedel–Crafts acetylation of cymantrene, a typical electrophilic aromatic substitution reaction, is much slower than that of ferrocene. Consequently, vinylcymantrenes are electron-deficient olefins and less reactive in olefin metathesis. For this reason, the present AMD/KR reactions

• of up to >99% ee. Vinylcymantrenes are electron-deficient olefins, and they are poorer substrates in olefin metathesis. For this reason, the AMD/KR reactions of rac-1a–c require a relatively high catalyst loading and the conversions tend to be lower. This study, together with our previous reports [29

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• binding components, including electron-deficient, electron-rich, and hydrophobic regions, which offer greater affinities towards biological targets. Structures of these compounds were confirmed through various spectroscopic analyses. The structure of compound 7 was confirmed using single-crystal XRD

• both hydrophobic and electron-rich/electron-deficient regions, enabling them to interact effectively with the active and inactive forms of the tyrosine kinase domain of the EGFR receptor. While the docking studies reveal a significant binding affinity of the synthesised compounds towards the EGFR

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• % yield. Mechanistically, WCl6 coordinates with Phen to generate the active tungsten species [G]. In cooperation with TMSCl as a Lewis acid, the catalyst activates the amide toward nucleophilic attack by forming an electron-deficient intermediate H that readily undergoes substitution. Palladium complexes

• (CO2) can catalyze transamidation reactions of amides by activating and stabilizing the tetrahedral transition state, which is a key intermediate (Scheme 16) [64]. Under a CO2 atmosphere, electron-deficient primary amides underwent smooth transamidation with butylamine to afford amide products 90 and

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• –Alder reactions with several electron-deficient dienes, furnishing distinctive methano-bridged structures (Figure 3C) [32][33][34][35]. Similarly, small cyclophanes are known to act as reactive dienes in Diels–Alder chemistry [36][37]. More recently, Lu and co-workers reported the unusually facile

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• direct i-substitution. Conclusion Umpolung reactivity of electron-deficient hexa(methoxycarbonyl)cycloheptatriene through its antiaromatic anion allows to introduce a connection between the cycloheptatriene core and an electrophilic reagent. The cycloheptatrienyl anion mainly exists as a conformer with

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• /organophotocatalyzed oxidative Smiles rearrangement of O-aryl aldehydes 26 has been developed using oxygen as the terminal oxidant under visible-light dual catalysis. This approach afforded highly functionalized 2-hydroxyarylbenzoates 27, tolerating electron-deficient and electron-rich substituents. The C–O bond

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• -dicarboxylates by its one-pot reduction–alkylation using NaBH4 in DMF followed by an alkylating agent. Base-promoted cyclization of electron-deficient 3-alkylthio derivatives furnished 2-aryl-, 2-aroyl-, and 2-cyano-substituted thieno[3,2-b]thiophenes, bearing a 3-hydroxy group. This protocol broadens access to

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• , a highly diastereoselective method for the synthesis of dihydrospiro[indoline-3,2'-pyrrole]-2-ones has been developed (Scheme 1, path a) [7]. This transformation proceeds via a Lewis acid-mediated conjugate addition of vinyl azides to electron-deficient alkenes, followed by denitrogenative

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• to explore additional protecting groups for the hydroxy functionality. Furthermore, given that alkylidene carbenes are electron-deficient and highly electrophilic, electron-rich C–H bonds are more prone to undergo C–H insertion [48]. Following this analysis, commencing from 20, after reduction, the

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• synthesis, they used an electron-rich and nucleophilic pyrrole as the precursor of the electron-deficient pyridine to enable a tandem sequence involving an intramolecular nucleophilic addition of the pyrrole to an iminium ion to form a key C–C bond. The pyrrole group was then converted to the desired

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• , initial examples of catalytic methodologies were based on chiral Lewis acid catalysis, with catalysts used in stoichiometric or sub-stoichiometric amounts [38][39]. Porter and Sibi disclosed the first enantioselective examples of conjugate additions to electron-deficient olefins by nucleophilic radicals

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• achieved ortho- and para-selective cyclization of methoxyamide-functionalized alkynes via ligand-controlled steric and electronic modifications (Scheme 17) [25]. When a flexible electron-deficient phosphate ligand L1 was utilized, the Au(I)-catalyzed cyclization of substrates 78 resulted in the formation

• ligand-controlled Au(I)-catalyzed intramolecular hydroarylation overcame key challenges of poor regioselectivity and limited applicability to electron-deficient substrates. In 2018, a gold-catalyzed divergent cyclization to access heteropolycyclic frameworks was reported by the Shi group (Scheme 18) [26

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• alkynylation of electron-deficient benzamide. In 2022, Ye presented an electrochemical synthesis of isoindolinone through 5-exo-dig aza-cyclization of 2-alkynylbenzamide (Scheme 9) [208]. By applying carbon cloth as anode, Pt as cathode and n-Bu4NOAc as electrolyte, the 5-exo-dig/6-endo-dig cyclization of 2

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• starting materials for different types of reactions including thermal isomerization to cyclopentenes [36][37][38] and 1,4-pentadienes [37][38], chemical electron-transfer oxidations to cyclopentene [39] and cycloaddition reactions with electron-deficient alkenes and alkynes [38][40][41] (Scheme 1b

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• proposed mechanism to 21 involved the formation of an electron-deficient, resonance-stabilized radical species, followed by intramolecular alkylation of the unactivated alkene to generate radical 29 via a diastereoselective 5-exo-trig cyclization step. Radical intermediate 29 was trapped by 2,4,6

• a single diastereomer (Table 1, entry 4). To explain this diastereoselectivity, we hypothesize that the C–O bond, which occupies an axial position in the proposed transition state TS-1, could avert an additional hyperconjugative interaction (σ*C-O/π) that renders the reacting C=C bond electron

• -deficient [28], thereby lowering the energy barrier for electrophilic radical addition. Increasing the reaction temperature to 70 °C proved detrimental, yielding only trace amounts of product 14 (Table 1, entry 5). Finally, replacing Mn(OAc)3·2H2O/Cu(OAc)2·H2O with other oxidants, such as ceric ammonium

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• , respectively. Correspondingly, 3a exhibits a deep blue emission at 453 nm with a quantum yield (ΦF) of 0.79, while a hypsochromic shift of the signal for 3b to 424 nm is observed and the ΦF value is decreased to 0.22 due to the electron-deficient character of the 3,5-bis(trifluoromethyl)phenyl groups. The

• to electron-deficient character, both the HOMO and LUMO energy levels of MC3 are obviously decreased in comparison to MC1 and MC2. Accordingly, the calculated energy gaps are 2.81 eV for MC1, 3.01 for MC2 and 3.08 for MC3, respectively, which are in line with the optical ones. In view of the

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• also been explored. Unlike sulphoxides, sulphones are not chiral. Both sulphone and sulphoxide are more electron-deficient than hemithioindigo, which induces a blue-shift of the absorption spectrum (Figure 16, centre) [88]. The photophysical properties of iminothioindoxyl 72 (Scheme 22, top), although

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