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

• , and advanced optical and energy materials. Review Visible-light-driven NHC/4CzIPN-catalyzed reactions Recently, Shu and co-workers developed a direct and innovative preparation of highly functionalized aryl amide derivatives 3 from aryl aldehydes 1 and substituted imines 2 under mild conditions in the

• , generating an N-centered radical species C. This species subsequently undergoes a rapid C–N cross-coupling with ketyl radical B. This cross-coupling method offers a transition-metal free route to highly substituted amides 3 from aldehydes 1 and imines 2, without the need for any external reductants or

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• significant attention in this context due to its flexibility, efficiency, and practical applicability. Since the late 1980s, many research groups have investigated the use of in situ-generated low-valent titanium [20][21][22][23][24][25] and niobium [26] reagents to promote the pinacol-type coupling of imines

• photocatalysts (Scheme 2). The combination of photoredox catalysis with imine activation enabled the reductive coupling of imines under mild reaction conditions, providing direct access to benzyl and aryl vicinal diamines with good to excellent yields. Organic electrochemistry represents an attractive and

• sustainable alternative; however, unfortunately, the electrochemical application is limited to only a few examples (Scheme 3). The electroreductive coupling of imines was first reported in the early 20th century by Law [42]. However, this initial method led to the formation of vicinal diamines with low to

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

• , Corminboeuf, Samanta, and König [6][31][32][33][34][35]. Although they do not possess an azo bond, heterocyclic imines are worth mentioning in this chapter due to their similarity to the azo-compounds and their straightforward synthesis. Substitution of the azo bond with an imine bond gives rise to

• heterocyclic imines [36][37][38]. The Z-isomers of the unsubstituted derivatives adapt different conformations: T-shaped for the N-phenyl and twisted for the N-pyrazoles. The half-lives follow the same trends already discussed beforehand. In contrast with the azopyrazoles, mono- and di-ortho-amination of the

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

• corresponding imines I and I′, as supported by the detection of imine I during GC–MS analysis. Both imines coordinate with the Lewis acid FeIII forming intermediates II and II′ with enhanced electrophilicity, respectively. Another equivalent of styrene (2a) attacks the electrophilic carbon, leading to the

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

• , imines, sulfur-containing groups, or alkyl chains) significantly expands their multifunctionality and broadens their application scope. Notably, CAs can be readily modified into amphiphilic macrocycles that can self-assemble with guests, and it exhibits superior advantages over crown ethers and

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

• an important role in medicinal and pharmaceutical chemistry [23][24][25] (Scheme 1a). Sodium hypophosphite exhibited good chemoselectivity – it selectively reduced imines while leaving other functional groups intact, e.g., nitro (NO₂), cyano (CN), alkene (C=C), and benzyloxy (OBn) groups. In contrast

• synthesis of imines and enamines [36][37]. In our reducing system H3PO2 could act as an effective reductant due to its high solubility in neat conditions (Table 1, line 1) (in form of morpholinium hypophosphite). Nonetheless reductive potential of hypophosphite is pH-dependent (−1.65 V at pH 14 vs −0.5 V at

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• Supporting Information File 1 for a schematic reaction setup) [21]. This method, previously tested in other reactions of nitrile oxides [21] and nitrile imines [22], was chosen as a reliable technique for the slow and consistent generation of the reactive dipole. In all cases the dipole precursor 4 was used

• for compounds 5a–l. However, in most cases, this method is more laborious due to the similarity in the retention factor values of the initial imines 2 and the reaction products. In this way, products 5i and 5j with good solubility in diethyl ester were isolated. A comparative analysis of compounds 5a

• greater involvement of the N1 electron pair in conjugation with the imide fragment of the dipolarophile and its deactivation in the reaction with nitrile oxide. This pattern is consistent with the one previously observed when studying the reactions of these dipolarophiles with nitrile imines [22]. It is

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

• , Suryavanshi and co-workers (2020) utilized PhI(OAc)2 to mediate the oxidative olefination of amines and Wittig reagents 415 to give the corresponding cinnamate esters 416–419 via formation of imines 421 (Scheme 87B) [148]. In addition, a gram scale operation has been conducted smoothly. 3.1.3 Carbene

• way via a non-metal strategy. For instance, Liu and Kardile (2019) reported Ag(I)-catalyzed olefinations of α-diazoester 422 and N-Boc-protected imines to afford the corresponding β-aryl-β-aminoacrylates 423–426 via formation of a Mannich–addition intermediate 428 which undergoes 1,2-hydride migration

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• Malkov reviewed the recent progress in the organocatalytic synthesis of chiral homoallylic amines. This important structural motif is typically made by asymmetric allylation of imines, and the authors describe various catalytic approaches as well as applications of these strategies in total synthesis [25

• organocatalytic cycloaddition reactions of unsaturated imines. A broad variety of activation modes, as well as catalyst structures, was covered and found to be useful in affording a diverse array of chiral N-heterocycles [27]. In my group, we recently became interested in atroposelective catalytic syntheses

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

• medicinal chemistry [58]. One of the most effective strategies for their synthesis is the addition of alkynes to imines or enamines, which is typically carried out under metal catalysis and elevated temperatures. This process requires the use of high boiling point solvents such as toluene, dimethylformamide

• (DMF), dimethyl sulfoxide (DMSO), or dioxane to achieve high yields. The assumed mechanism is initiated by activation of the C–H bond of the terminal alkyne by a metal catalyst. The resulting metal acetylide reacts with the imine/enamine through a nucleophilic addition. Because imines/enamines are

• difficult to separate [86][87][88]. Probably, the high reactivity of the imines generated by formaldehyde leads to their polymerization [84] or even to the incorporation of other nucleophiles present in the reaction mixture, such as the solvent or a second molecule of the amidine component (Scheme 32) [84

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

• optimization of the substituent on the 1-position of imines was conducted (Scheme 2). In most cases, the products were obtained in high yields with moderate to high enantioselectivities; the sterically less-hindered methyl-substituted substrate 7b was found to be better than the other substrates. The bulky

• phenyl- or trityl-substituted 7c and 7d yielded products with decreased enantioselectivities, likely due to the inhibition of the interaction between the imines and the chiral catalyst by hydrogen and/or halogen bonding. From these observations, the substituent on the 1-position strongly affected the

• . From these results, the substrate scope was conducted using 9b as a catalyst. First, the scope for the imines was carried out (Scheme 4). 5-Methyl-substituted 7f provided the corresponding product 17f in 87% yield and 65:35 diastereomeric ratio with 85% ee and 58% ee for each. 5-Chloro-substituted 7g

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• . First, the alkyl handles bearing a primary hydroxy group were introduced and then converted into the electrophile of choice. More specifically, to furnish compounds 4b–d, precursor 9 was treated with the corresponding amino alcohols in the presence of a desiccant. The imines formed were subjected to

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• ) [38]. To capture both stability and solubility, we turned to Mastalerz’s post-functionalization chemistry [286][300][304][306][358][359][360][361][362], in which imines are oxidized by a Pinnick oxidation to amides [286][360][363][364], an approach gaining popularity [46][262]. Importantly, we were

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

• ]. Three-component coupling of amines, aldehydes or ketones, and terminal alkynes catalyzed by Cu(OTf)2 is a fruitful tool for the production of α-substituted propargylamines 10 (Scheme 7) [20]. The reaction involves the alkynylation of the corresponding imines formed in situ and provides higher yields

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

• atroposelective deracemization of biaryl hydroxy aldehydes 55a–k [37]. NHC catalyst C18 afforded a range of axially chiral benzonitriles 56a–k in high yield and enantiomeric purities (Scheme 18). The reaction likely proceeds via the initial formation of racemic imines, which is followed by the formation of aza

• diastereomeric ratios in a couple of cases. On a 1 mmol scale with reduced catalyst loading the reaction proceeded in a similar fashion with good yield and enantioselectivity (70%, 89% ee). The Povarov reaction of imines 87a–h and alkenylindoles 88a–i catalyzed by CPA (R)-C23 was utilized to give asymmetric

• be carried out in a one-pot fashion with comparable results and without significant variation from the two-step procedure. Utilization of the Povarov reaction and subsequent oxidation by DDQ was also done by Wang et al. in 2020 [54]. In situ-formed imines from anilines 91 and benzaldehydes 92 were

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• have been reported [12]. These reagents have proven effective in delivering azides (I) [13], amides (II) [14], aliphatic cyclic amines (III) [15], phthalimidates (IV) [16], imines (V) [17], sulfoximides (VI) [18], carbazoles (VII) [19], secondary (VIII) [4] and primary (IX) [20] amines (Figure 1). 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

• imines; asymmetric organocatalysis; cyclization; N-heterocycles; inverse electron demand aza-Diels–Alder reaction; Introduction Nitrogen-containing heterocycles are abundant scaffolds present in natural products, biologically active compounds, pharmaceuticals, synthetic agrochemicals, and functional

• materials [1][2]. Due to their importance, different synthetic routes involving stoichiometric and catalytic approaches have been developed. The α,β-unsaturated imines, also known as conjugated imines or 1-azadienes, are useful precursors for the construction of aza-heterocycles. Due to their structure

• , they can be attacked by a nucleophile and undergo a 1,2-addition or conjugate addition leading to the production of allylic amines or aliphatic imines, respectively. They can also behave as C4 synthons in cycloaddition reactions such as the aza-Diels–Alder reaction, giving access to nitrogen-containing

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

• the synthesis of cyclic imines using a one-pot protocol involving Grignard addition to a cyano group followed by PhI(OAc)2 (Scheme 30) [51]. The authors used p-tolylmagnesium bromide for both the arylation of the unsaturated carbonitriles 55 and as a bromide source. Bromocyclisation was achieved using

• PhI(OAc)2, which formed a range of 5- and 6-membered bromomethyl cyclic imines 56 in good yields from unsaturated imines 57. Xia and co-workers reported the bromocyclisation of indole derivatives 58 (Scheme 31) using PIDA and CuBr2 as the oxidant and bromide source, respectively [52]. Racemic pyrrolo

• of cyclic imines 45. Synthesis of brominated pyrrolo[2,3-b]indoles 59. Bromoamidation of alkenes. Synthesis of brominated cyclic guanidines 61 and 61’. Intramolecular bromocyclisation of N-oxyureas. The formation of 3-bromoindoles. Bromolactonisation of unsaturated acids 68. Synthesis of 5

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• .20.241 Abstract An efficient and facile synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives was developed through the isocyanide-based multicomponent reaction of isocyanides, gem-diactivated olefins, and cyclic imines such as dibenzoxazepine, dibenzothiazepine

• great attention in biomedical applications, clinical diagnostics, and conjugate materials. Keywords: cyclic imines; dibenzothiazepine; dibenzoxazepine; isocyanides; multicomponent reactions; pyrrole; triazolobenzodiazepine; Introduction Pyrroles and their derivatives are important N-heterocyclic

• ) [42][43]. Another I-MCR for forming pyrroles is the in situ formation reaction of the zwitterion III, known as Huisgens 1,4-dipole. The latter is formed by the reaction of imines with acetylenedicarboxylates and can be trapped by an isocyanide through a [4 + 1] cyclization reaction to synthesize

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• remains tenuous. Indeed, until recently, mixed alkylzinc species were only employed by Carretero and co-workers in related nucleophilic additions to activated imines under Cu catalysis [22]. In 2022, our group demonstrated that alkyl iodides offer a reliable source of heteroleptic organozinc compounds

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• fluoroalkylated amines 15 with high optical purity could be easily prepared through [1,3]-proton shift reactions of optically active imines 14 which in turn were readily synthesized by condensation of various perfluoroalkyl ketones with optically active (R)-1-phenylethylamine (Scheme 2a) [25][26][27][28][29][30

• ][31][32]. Therefore, we envisioned that optically active tetrafluoroethylenated amines 17 could be synthesized by applying the [1,3]-proton shift to optically active imines 16 derived from readily prepared tetrafluoroethylenated ketones (Scheme 2b). In this paper, we describe the details of the [1,3

• ]-proton shift reaction of various tetrafluoroethylenated imines. Results and Discussion The preparation of substrates used in this study was as outlined in Scheme 3. Namely, the zinc reagent was prepared from commercially available 3,3,4,4-tetrafluoro-1-butene (18) [33] and reacted with various acid

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

• reactants. Therefore, based on the previous studies on the oxidative 3-component Ugi–Joullié reaction [22][23][24] and our precedent experience [25][26][27], we speculated that cyclic imines could be good substrates for our reaction, thanks to their higher rigidity and stability. As depicted in Scheme 2b

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

• and cross-coupling of different kinds of amines for approaching symmetric and unsymmetric imines [76]. This method achieved the bioconjugation of several amino acids with benzylamine, the use of phenylalanine (Phe), serine (Ser), and isoleucine (Ile) as substrates led to 85%, 59%, and 29% yield

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

• Nikolay S. Kondratyev Andrei V. Malkov Department of Chemistry, Loughborough University, Loughborough, LE11 3TU, UK Faculty of Science and Engineering, University of Wolverhampton, Wolverhampton, WV1 1LY, UK 10.3762/bjoc.20.201 Abstract In recent decades, the chiral allylation of imines emerged

• as a key methodology in the synthesis of alkaloids and natural products with 4-, 5- and 6-membered cyclic amine motifs. Initially reliant on stoichiometric reagents, synthetic chemists predominantly used N-substituted chiral imines, organometallic chiral reagents and achiral reagents with an

• equimolar chiral controller. However, recent years have witnessed the rise of asymmetric transition-metal catalysts and, importantly, organocatalytic allylation, reshaping the landscape of modern synthetic chemistry. This review explores the latest developments in the asymmetric allylation of imines

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

• catalyzed by primary amines in transformation requiring the formation of the imines without catalyst deactivation. The study underscores the potential of mechanochemistry in broadening the scope of organocatalytic and stereoselective transformations including the application of rather unexplored thioesters