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

• of the electrophile. We thus identified aldehydes 9 and 10 as suitable branching points, which were easily derivatized to their aminomethyl-modified preQ1 analogs by reductive amination (Scheme 3). Their syntheses by Raney-Ni reduction of nitriles 7 and 8, previously described by Gangjee and co

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• -functionalized aldehydes with at least one stereocenter in the C3 position. The results, which are collected in Table 5, show that the kinetic resolution depends on the characteristics of the substituents. The best results were achieved for the Michael adduct 12, derived from acetylacetone, with R1 = Ph (entry

• conditions tested. Similarly, the resolution of nitro aldehydes 16 and 17, prepared by Michael addition of nitromethane to α,β-unsaturated aldehydes (entries 16 and 17, Table 5), was tested, and the same results were obtained as in the cases of the malonate derivatives. These results indicate that dicarbonyl

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

• -based porous organic cages have been a popular choice for study [377][379][406][407][408], as have MOCs [208][376][386]. Much focus remains on the prediction (and automation) [409] of the formation of cavities by probing combinations of, e.g., amines/aldehydes or metals/ligands to identify structures

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• role in most cases is to generate highly reactive species in situ from the nucleophilic reaction component. This can subsequently interact with other reaction components to form target products. Compared to the crotonic condensation products of other aliphatic and aromatic aldehydes, methylidene

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

• reactions conducted step by step. Providing acyclic compounds A three-component Strecker-type condensation of aromatic aldehydes, amines, and cyanides under mild reaction conditions furnishes α-aminonitriles 1 in good to high yields (Scheme 1) [15]. The reaction failed only in the case of acetophenone

• . The Mannich reaction with aromatic aldehydes and cyclic amines was performed efficiently on 2-naphthol, by using SiO2-supported copper triflate under solvent-free conditions, without an additional co-catalyst or additive (Scheme 3) [17]. The treatment of stoichiometric amounts of arylaldehydes

• ]. 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

• activation of propargylic aldehydes with catalyst Int-1. Another critical feature was the ability of the organocatalyst to promote the Z-selective isomerization of Int-2 to Int-3. In a related fashion, Wang and co-workers developed an atroposelective heterocycloaddition [19]. The iminium-activated alkynals 4

• are of interest and have been recently investigated by Jørgensen and co-workers. The authors employed an enantioselective aminocatalytic cycloaddition between 5H-benzo[a]pyrrolizine-3-carbaldehydes 22 and naphthyl-substituted nitroalkenes, α,β-unsaturated ketoesters, or α,β-unsaturated aldehydes 23

• -catalysis recently led to an array of intriguing transformations. Axially chiral styrenes 26 were assembled via the NHC-catalyzed reaction of propargylic aldehydes 25, sulfinic acids, and phenols [28]. The crucial step of this transformation is the 1,4-addition of the sulfinic anion to the triple bond of

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

• reported, providing a novel methodology for the construction of α,β-unsaturated imines [4]. There are different types of α,β-unsaturated imines, such as the acyclic imines aldimines, ketimines, or dienimines, depending on whether they are derived from aldehydes, ketones, or doubly unsaturated ketones

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• included oxidation of aldehydes 4 with Oxone to acids 5 and the conversion of the latter into acid chlorides with thionyl chloride. The first reaction sequence was suitable for obtaining compounds 1a–c,e,f with substituents tolerant to radical reaction conditions. A significant advantage of the method is

• separate impurities. In these cases, as well as in reactions giving low aldehyde yields in the first step (4b,d), the second developed reaction sequence turned out to be more effective. In the second approach, the oxidation of aldehydes 4 with Oxone to acids 5 occurs with yields close to quantitative, and

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

• AChE, while pyrazole scaffolds possess the ability to reduce the tau and β-amyloid dual aggregation. Benzofuran-pyrazole aldehydes were employed in the Ugi azide reaction to give the desired hybrids. From the screened compounds, 2a, 2b, 2c, 2d, 2e, and 2f demonstrated notable efficacy in regulating the

• quinazolinone scaffold. They have obtained new benzochromenopyrimidinones, abbreviated as BCPOs, whose synthesis has been accomplished in two steps. First, a microwave-assisted reaction of ethyl cyanoacetate, selected aromatic aldehydes, and 2-naphthol was performed. The second step was the condensation of the

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

• addition of furan-based silyloxydiene synthons to a variety of achiral aldehydes using four different calix[4]pyrrole macrocycles (3, 4, 11, and 12) as organocatalysts (Figure 3) [38]. These calixpyrrole macrocycles acted as hydrogen-bond donors, activating substrate aldehydes through hydrogen-bonding

• -workers reported using metal-free planar H2TPP (18) as a photocatalyst for the photoredox-α-alkylation of aldehydes with ethyl diazoacetate [91]. This reaction achieved an impressive product yield up to 84%. Control experiments showed that omitting any one of the reaction components – such as the

• the electrochemical and photochemical properties of the catalyst was crucial for facilitating photoelectron transfer (PET) processes in these photoredox systems. De Oliveira and co-workers reported metal-free porphyrins as photoredox catalysts for the synthesis of α-arylketones/aldehydes by arylation

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

• , University of Miami, 1301 Memorial Drive, Coral Gables, Florida 33146-0431, USA 10.3762/bjoc.20.255 Abstract Distilled propargyltrichlorosilane with >99% isomeric purity was prepared for the first time, and its asymmetric catalytic regiospecific addition reaction to aldehydes was developed through a

• . Accordingly, the development of efficient access to optically active chiral α-allenic alcohols continues to be of significant interest in organic chemistry [11][12][13]. The asymmetric catalytic addition of allenylation reagents to aldehydes provides direct access to chiral α-allenic alcohols in an

• extensively investigated allylation with allyltrichlorosilane [58][59]. In light of the excellent reactivity and promising selectivity displayed by catalyst 8 for the model reaction, we proceeded to evaluate its ability to enantioselectively promote the allenylation of various aldehydes (Scheme 5). The

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• [58] was prepared in the first step via three-component reaction between tetracyanoethylene, cyclopentanone, and hydrogen chloride. Then, multiacceptor compound 2 was involved in the condensation with aromatic aldehydes bearing electron-donor groups. As a result, a series of new push–pull molecules

• containing various numbers of substituents at the donor site, which differed in their electron-donating strength, was obtained. It was found that the reaction of pyridine 2 with aromatic aldehydes occurred with complete stereoselectivity – only the E-isomer was obtained as the reaction product. The

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

• Fe-catalyzed decarbonylative alkylation–peroxidation of alkenes 130 with aliphatic aldehydes 131 and TBHP to provide chain elongated peroxides 132 was developed (Scheme 44a) [103]. Aliphatic aldehyde 131 were used as the sources of 1°, 2°, 3° alkyl moieties via decarbonylation strategy. The proposed

• and 134 with TBHP and aldehydes as alkyl sources, producing long-chain ketones 136 via intermediate peroxide 135 formation (Scheme 44b) [104]. Acyl fragment: A breakthrough on difunctionalization of C=C double bonds using TBHP and aldehyde has been achieved in 2011 by Li and co-workers (Scheme 45a

• ) [105]. A three-component reaction of alkenes 137, aldehydes 138, and hydroperoxides catalyzed by FeCl2 to β-peroxy ketones 139 has been realized. The authors proposed the involvement both as acyl and tert-butylperoxy radicals into the reaction pathway. The tert-butoxy radical A and tert-butylperoxy

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• –CH2–(CF2)n–COOCH3 (n = 2,4,6, Tf = triflate) were synthesized. The triflates were reacted with 2-hydroxy-3,4,5-trimethoxybenzaldehyde via Williamson ether syntheses. The resulting electron-rich compounds were used as aldehydes in the Rothemund reaction with pyrrole to form ester-substituted porphyrins

• ester-functionalized aldehydes 22, 23, and 24. Conditions: a) NIS, TFA, Na2CO3, MeCN, reflux, 18 h; b) Cu2O·H2O, 2-pyridinaldoxime, TBAB, CsOH, H2O, N2, rt, 18 h; c) Cs2CO3, DMAc, N2, rt, 3 h. Porphyrin synthesis. a) Rothemund porphyrin synthesis of metal-free porphyrins 26, 27, and 28; b) metalation of

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

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• ). Hydrazones derived from aromatic aldehydes (1a–p) were first investigated. It turned out that para-substituted compounds with electron-rich groups (e.g., OMe, OBn), halogens (Cl, Br, I), and electron-withdrawing groups (e.g., CF3) were smoothly trifluoromethylthiolated. In the same vein, meta- and ortho

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

• electrophilic sites simultaneously in their structure, these zwitterions are able to participate in various cyclization processes, especially for the synthesis of pyrroles [37][38][39][40]. For example, Li et al. developed a one-pot four-component reaction (4-CR) of malononitrile, aldehydes, and isocyanides

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

• stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines. A variety of primary, secondary, and tertiary organozinc reagents as well as secondary amines and aromatic aldehydes could be used for the straightforward preparation of α-branched

• various aromatic aldehydes could be used in the multicomponent coupling. Interestingly, functionalized organozinc reagents gave the multicomponent coupling product, except for the cyanated organozinc compound 2d, which only provided traces of the expected α-branched amine. It can be noted that in sharp

• , a secondary aniline only furnished traces of the expected product. Aliphatic aldehydes also failed to deliver the multicomponent adduct. Conclusion In conclusion, we have shown in this work that alkyl bromides can be used instead of alkyl iodides in a direct zincation–multicomponent organometallic

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• with aldehydes 8, 9, and 10 under Lindsey conditions [42] utilizing BF3·OEt2 and DDQ [43] to achieve porphyrins 4, 5, and 6, which were not isolated and instead reacted immediately. Ni(II)porphyrins 11, 12, and 13 were prepared by reacting porphyrins 4, 5, and 6 in toluene for 18 hours using Ni(II

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

• -pot multistep synthesis of unprecedent 2,3-diaminoindolenines using graphene oxide (GO) as heterogeneous catalyst [21]. The protocol involves the three-component Ugi (3C-Ugi) reaction between aldehydes, isocyanides and 2 equivalents of electron-rich anilines to give α-aminoamidines, which undergo a C

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• versatile method using decarbonylation of benzofuranone followed by oxidation, that produces only CO2 as a non-toxic side product, is considered less hazardous. Although decarboxylation of aldehydes, carboxylic acids, and ketones are well known, albeit using metal catalysts, decarboxylation methods for

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• animal kingdom that serve as signals, such as the aldehydes syn-4,6-dimethylundecanal and 4,6-dimethyldodecanal and their corresponding alcohols, which act as male sex and trail-following pheromones in termites [31][32]. Diketopiperazines The GC–MS analysis also revealed the presence of at least five

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• traces of residual moisture. Reactions were monitored by thin-layer chromatography (TLC) using E. Merck silica gel plates and components were visualized by illumination with short wavelength UV light and/or staining (ninhydrin or basic KMnO4). All aldehydes were distilled right before use. All aryl

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

• electrolyte, and carbon felt and platinum plate as electrodes, the intramolecular hydroamination proceeded smoothly, yielding azetidines in moderate to good yields. This method was applied to the LSF of celecoxib, zonisamide, and dansyl amide (Scheme 33a). Additionally, the allylation of aldehydes also

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• molecular recognition [12][46]. Despite extensive research, challenges remain in the acid-catalyzed resorcin[n]arene synthesis, for example: 1) reaction times for simple resorcin[n]arenes starting from aliphatic aldehydes and resorcinol generally require multiple days and up to a week (Scheme 1a) [9][26]; 2

• ) use of 2-substituted electron-poor resorcinols with aldehydes larger than acetaldehyde produce intractable mixtures leading to no product isolation [9], in turn access to halogenated or deactivated electron-poor resorcin[n]arenes typically require an extra step as shown in Scheme 1b [8][56][57][58][59

• presence of various aldehydes featuring different alkyl chains, all of which exhibited high isolated yields (Scheme 2, compounds 1a–e). Interestingly, literature reports commonly show lower yields as the aldehyde alkyl chain increases in length where commonly refluxing temperatures are required [9][74][76