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

• underwent ketone release and amine-ketone condensation to form iminium ion 27. Under the same acidic conditions, enamide 26 underwent hydrolysis and tautomerization to form enol 28. Conjugate addition of enol 28 to iminium ion 27 gave 29 for the subsequent intramolecular Mannich cyclization to deliver 30

• hemiaminal opening and amine–ketone condensation, iminium ion 65 was produced for the next pyrrole nucleophilic addition to form a strategically important C–C bond and afford 66, which was protected as Boc carbamate in the same pot to give 67 in 96% yield from 64. In this tandem sequence, the nucleophilicity

• 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

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• ) step to form the zwitterionic alkoxide E and the oxidized DIPEA iminium ion F. Notably, small signals consistent with trace amounts of the alkoxide species E were occasionally detected in the crude 1H NMR spectra of reactions conducted both in the presence and absence of a photocatalyst (see Supporting

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• water led to the drop of the yield while comparably low amounts (less than 0.7 equiv) were favorable (see Table S2 in Supporting Information File 1). This influence could be explained by hindering of the iminium ion formation in the presence of water. Thus, the optimization of the reaction conditions

• system is more efficient than the earlier described usage of the pure NaH2PO2: higher solubility of the potassium, rubidium and cesium salts compared to the sodium and lithium and a proper pH of the reaction medium. Acidic catalysis strongly accelerates the rate of hemiaminal and iminium ion formation

• us to propose a mechanism of the developed reaction. Fast proton exchange between tautomeric forms of carbonyl compounds or iminium cations and enamines was shown in the reaction with D3PO2. A combination of four-electron reductants KH2PO2 and H3PO2 are likely to transfer H-atoms to iminium ion

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• resulting iminium ion can be readily captured by a wide variety of nucleophiles, including alkenes and alkynes. These aza-Prins cyclizations have potential applications in the synthesis of natural alkaloids, as exemplified by She’s total synthesis of (−)-dihydrolycopodine and (−)-lycopodine [17]. These

• quaternary center in a single step. As depicted in Scheme 1, key enamide 1 was prepared from (R)-pulegone in 6 steps. In the presence of the weak acid H3PO4, protonation of 1 generates a stabilized iminium ion 2, which then undergoes a 6-exo-trig cyclization to deliver 4 after hydration of cation 3. Notably

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

• , in which the copper catalyst (CuCl, 15 mol %) only activates the C–H bond of the terminal alkyne, and the resulting nucleophile A reacts with the iminium ion F generated from CH2Cl2 and the secondary amine via an aminal intermediate E (Scheme 24) [68]. However, Yu et al. found no evidence for the

• secondary amines such as piperidine or pyrrolidine afford an aminal or an iminium ion, in general under high temperature or pressure conditions, which is not the case for the AHA coupling [69][70]. Despite these cases, the absence of evidence in terms of iminium ion generation confirms that the AHA coupling

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

• light (λ = 750 nm), followed by triplet energy transfer to molecular oxygen, generating singlet oxygen as the active species. Similarly as in the case of the Furuyama et al. study, the singlet oxygen subsequently oxidizes the amine substrate to an iminium ion, which reacts with a cyanide nucleophile to

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

• (Scheme 16) [33]. The reaction, which occurs with formation of C–C, C–N and C–O bonds, involves a nucleophilic addition of the activated alkyne XIV to the in situ-generated iminium ion XV, followed by cyclization to form a quinoxalin-2-one intermediate XVI. A subsequent 5-endo-dig cyclization involving

• additive. Some control experiments support a mechanism whose key intermediates are the formation of the iminium ion XIX, originated from aniline with formaldehyde which serves as the C1 building block, and the generation of the cyclic α,β-unsaturated ethers XX by Cu(OTf)2-catalyzed dehydrogenation of the

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

• excellent enantioselectivities (70–95% ee) when using chiral phosphoric acid XIV (Scheme 16). Mechanistic studies were performed to unveil whether a concerted or stepwise mechanism is taking place, such as trying to trap a possible iminium ion intermediate. The outcome of those experiments pointed towards a

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

• oxidize the substrate, which reacted with the 3-methoxyaniline and tert-butyl isocyanide affording the α-aminoamidine, albeit inefficiently. Besides, the role of GO in the 3C Ugi reaction remained unclear. Actually, the iminium ion formed after the oxidation is already quite activated to react with

• isocyanide without the presence of a catalyst. In order to establish the role of GO we carried out the 3C Ugi-type reaction starting from iminium ion 1a, freshly prepared by visible light irradiation in the presence of bromochloroform [28]. This protocol resulted quite convenient as can be conducted under

• -methylaniline step by step (Scheme 4). While the 3C Ugi-type reaction between iminium ion 1a, p-methylaniline and tert-butyl isocyanide gave product 2p in good yield, when the α-aminoamidine was subjected to the oxidation–cyclization step, the starting material was completely converted, but 3p was not isolated

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• the C-nucleophile on 81 is very slow, which determines the chemoselectivity of the reaction. Complex 83 of the iminium ion and the catalyst then reacts with allylsilane 84 through an open, type 2 [33] transition state from the exposed enantiotopic face, as in int-79, to afford product 85 and to

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

• [15][16] or iminium-ion catalysis [17] under ball-mill conditions are scarce, in contrast to the abundance of transformations catalyzed by such covalent catalysis. Among the numerous organocatalytic reactions facilitated by primary amine-based iminium ions, Michael-type additions deserve special

• both conditions. This result could be ascribed to the lower affinity of the oxo-ester to form active nucleophiles in comparison to the more favorable enolization of thiomalonates. The stereochemical outcome of the thiomalonate’s addition could be rationalized by the assumption the iminium ion

• planetary mill. Further variations of system A concerned the acid’s role. However, no impact of the acid was noted while using the amino acid derivative AC-2, but the dramatic loss of selectivity was observed in the case of chiral phosphoric acid’s application AC-3. Thus, it is rather unlikely the iminium

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• [34]. In reductive amination, the substrate is usually an aldehyde or amine. After the formation of the iminium ion, it is reduced with the appropriate reagent to form the N-methylated amino acid. Different methods have been established using for example benzaldehyde as a protection group, sodium

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• presence of one equivalent Brønsted acid additive A5, the catalyst II generates the monoprotonated diamine II-A5. The condensation of the primary amine moiety in II-A5 with the carbonyl group of the α,β-unsaturated ketone 1b in presence of the Brønsted acid leads to the formation of the iminium ion

• assembly 4 (Scheme 5). It is known that Brønsted acids facilitate the iminium ion formation step [38][39] and the counteranion of the acid plays an important role in the stereocontrolling event [38][40]. On the other hand, the protonated quinuclidine nitrogen atom of the catalyst II (in the iminium ion

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• catalytic cycle. Similar to what was previously observed, the elimination of the trichloro(alkoxy)ferrate(III) anion from intermediate C provides the iminium ion D, susceptible to nucleophilic attack by a water molecule present in the reaction medium, leading to the carbinolamines 6. This latter synthesis

• iminium ion D formed in the second catalytic cycle (Scheme 4), and its sole formation is ascribable to the capability of molecular sieves of sequestering MeOH eventually formed, shifting the equilibrium towards 7. Noteworthy, in compounds 5a–r, 6a–p and 7, the newly created heterocyclic nucleus represents

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• products) were found to be somehow unstable when concentrated to dryness during work-up. We hypothesize that a possible cause of such instability might consist in the formation of a highly electrophilic iminium ion upon protonation of the hemiaminal ether by silica or glassware acidity and further

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• report from the literature [24] a plausible reaction mechanism is shown in Scheme 6. It involves the nucleophilic attack of the aminopyridine 1 to the HPW-activated carbonyl compound 2, followed by iminium ion formation (iii) and [4 + 1] cycloaddition with the isocyanide. A 1,3-hydrogen shift yields the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• the phthalimidyl anion within the chiral pocket of the phosphate catalyst to form complex 55, before enantioselective addition to the iminium ion affords product 56. NHPI esters can also engage in π–π interactions with electron-rich species to generate charge-transfer complexes that can absorb light

• formation of α-amino radical 107 through photoinduced SET followed by fragmentation. Subsequent oxidation of 107 by radical cation q-Ac•+ afforded iminium ion 108 before nucleophilic addition of the in situ-generated tetrachlorophthalimyl anion (–TCPhth) led to the formation of aminal product 105. Of note

• (sp3)–N cross-coupling products. On one hand, in-cage electron transfer from radical 107 to BiII complex 130 can generate iminium ion 108. Alternatively, intermediate 108 could arise from complex 131 by reductive elimination. Ultimately, the iminium ion can be trapped by the nitrogen nucleophile to

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• reaction for the synthesis of polyfunctionalized cyclohexenes bearing multiple stereocenters. The reaction is promoted by a chiral secondary amine, which is capable of catalyzing each step of the process activating the substrates through enamine and iminium ion catalysis towards a Michael/Michael/aldol

• intercepts the nitroalkene 3 in a Michael-type addition forming intermediate B. Hydrolysis regenerates catalyst 1 that can then selectively condense with the α,β-unsaturated aldehyde 4 to form chiral iminium ion intermediate C. Iminium ion C reacts with intermediate B in a further Michael-type reaction. The

• nitronate to the α,β-unsaturated iminium ion, should be tackled to improve the diastereocontrol. All efforts to discriminate the two faces of the nitroenolate during the addition proved unproductive during the optimization, therefore, a potential epimerization was envisaged during the course of the reaction

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• carbonyl carbon to form the 5-membered ring E bearing the iminium ion. Finally, N-substituted amines 67 were obtained after deprotonation/protonation, dehydration, and aromatization steps as shown in Scheme 32b. In another report, Ozaki et al. [87] used the Clauson–Kaas approach to synthesize sulfonic

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• persulfate (K2S2O8) as the exclusive reagent [14]. The mechanistic study revealed that an initial oxidation to an iminium ion could be the key intermediate in the intramolecular cyclization step. In sharp contrast, when N-aryl(benzyl)amines that do not have an ortho-substituted nucleophile in aniline ring

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• reaction with the α-aminoether 118. This reagent released an iminium ion into the reaction medium that reacted with the Al enolate 117 [66]. Furthermore, the Mannich adduct was then reacted with Grignard reagents that replaced the dimethylamino group (Scheme 30). Alexakis and co-workers also investigated

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• single diastereomers. This reaction outcome was attributed to a potential cis–trans isomerization of the C–N double bond upon iminium formation (Scheme 4). In this respect, the mixing of imine 18 with the α,β-unsaturated acyl chloride 6 is expected to form the iminium ion 20a with Z-configuration. A

• chloride-mediated iminium E–Z isomerization may take place through the intermediacy of α-chloroamide 21. The aza-Nazarov reaction of the more stable E-iminium ion 20b is expected to proceed faster due to steric considerations giving the major diastereomer 19 whereas the less stable Z-iminium ion 20a would

• product in pure form from a crude reaction mixture failed. However, when a mixture of imine 5a and methacryloyl chloride (31) was stirred in a biphasic mixture of CH2Cl2 and aqueous NaHCO3 solution, we were able to isolate and fully characterize aldehyde 32 which would form via the hydrolysis of iminium

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• from the indoline to B(C6F5)3. The resultant iminium ion is deprotonated by a second indoline molecule with the formation of an ammonium ion and the final indole. The ammonium ion reacts with a HB(C6F5)3 anion with the release of a H2 molecule and the regeneration of B(C6F5)3 for the next catalytic