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

• developed in which the alkene compound has been replaced with other surrogates for electrophilic addition, such as ketones [32][33][34]. In the case of the carbonyl component, it is generally an aromatic aldehyde [30][33][34] and there are not many reports on using formaldehyde in the Povarov reaction. In a

• , methyl aryl ketones, and DMSO under iron(III) catalysis and using K2S2O8 for its activation [39]. The proposed mechanism is very close to those described above, with the methyl aryl ketone taking part of the reaction in place of the styrene component in the Povarov cyclization. In this case, the imine

• reaction, affording 2-arylquinolines III. All of these examples showed the versatility of DMSO as a methylene source in the synthesis of substituted quinoline compounds (structures I, II, and III; Scheme 8 and Scheme 9), using different substrates (such as styrenes, alkynes, and methyl aryl ketones) and

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• starting materials to study the vinylogous functionalization with alkyl trifluoropyruvates. The synthesis of compounds 3 was accomplished by the reaction of cyclic ketones 1 and 5-aminopyrazoles 2 in the presence of acetic acid (Scheme 1) [30][31]. Cyclohexenones 1a–c provided the corresponding products

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

• other Michael adducts prepared by reacting with differently activated ketones, the enantiomeric ratio of the isolated anti-diastereomer was excellent (entries 1 and 10–13, Table 5). Interestingly, the method also provides good resolution for Michael adducts 8 and 9 synthesized by reacting keto sulfones

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• 2-(indolin-2-yl)-1,3-tropolones [5]. Unlike the cross-aldol reaction of o-chloranil with methyl ketones [13][14][15], which is always accompanied by the removal of one of the chlorine atoms from the seven-membered ring, the acid-catalyzed reaction between methylene-active heterocyclic compounds and

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

• properties beyond 645 nm, providing access to low-energy red-light-driven chemical transformations. The catalysts have successfully facilitated the dehalogenation of 18 different α-halo ketones 33 with minimal catalyst loading (0.1 mol %) and high yields under mild conditions. For instance, bromoacetophenone

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• reactions of isatins with alkyl acrylates, acrylonitrile, and other activated alkenes [26][27][28][29]. Due to the stronger electron-withdrawing effect of the oxindole motif, MBH carbonates of isatins showed higher reactivity than that of the normal MBH carbonates of normal ketones [30][31][32][33][34][35

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

• was crucial for the formation of the organozinc reagent (Scheme 19) [36]. Spiro-2,3-dihydroquinazolinones 26 were formed exploiting a one-pot multicomponent reaction, using isatoic anhydride, ketones and primary amines. The isolation of the amide intermediate XXIII obtained by the copper-catalyzed

• of promoting the three-component cascade cyclization of 2-formylbenzonitriles, alkyl aryl ketones, and diaryliodonium salts to afford 2-arylisoindolinones 32 (Scheme 24) [41]. It is conceivable that the reaction starts with the formation of an N-arylnitrilium cation XXXI that, after hydrolysis

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

• biaryl ketones 84 with cyclohexanones 85 mediated by the second-generation chiral phosphoric acid C26 led to the formation of tetrahydroacridines 86 (Scheme 28) [52]. This Friedländer reaction provided products 86 in moderate to good yields with consistently high enantiomeric purities and high

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

• demand aza-Diels–Alder reaction (IEDADA) of β,γ-unsaturated ketones 23 and benzofuran-derived azadienes 11 [31]. The procedure enables the straightforward synthesis of benzofuran derivatives 24 bearing an additional tetrahydropyridine ring in good yields (51–94%) and excellent enantioselectivities (90–96

• ketones 42 [37]. With this transformation polysubstituted cyclohexanes 43 bearing four consecutive stereocenters are afforded through efficient one-pot cyclization with good yields (43–95%) and with high enantioselectivities (80–97% ee) (Scheme 15). In general, 1-azadienes 14 with different substitution

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

• intramolecular SNAr reactions. Ugi-4CR/deprotection/cyclization (UDC) strategy: In the UDC approach a protected amine and an electrophilic functional group like esters or ketones are used. Convertible isocyanides can also be employed. Once the Ugi reaction is completed, the protecting group is removed, and the

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

• propargyltrichlorosilane [35][36] (Scheme 2). Other notable asymmetric catalytic approaches to prepare α-allenic alcohols (R2 = H) include the Corey–Bakshi–Shibata reduction of allenyl ketones [37], enzymatic [38][39][40], non-enzymatic [41] kinetic resolution of racemic α-allenic alcohols, and asymmetric 1,4

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

• ketones 108 and TBHP to alkenes 107 (Scheme 38a) [94] and methacrylamides and methacrylates 110 (Scheme 38b) [95] with the formation of γ-peroxyketones 109 and 112 have been demonstrated. The reactions are believed to proceed via thermal decomposition of alkenyl peroxide B, which is formed from geminal

• in Fe-catalyzed difunctionalization of alkenes with TBHP resulting in δ-peroxy ketones 126 and δ-peroxy esters 129 (Scheme 43a and 43b). In the case of siloxy cyclopropanes 128 the authors used TBAF as the additive to remove the TMS-protecting group. Oxidation of the resulting anion A with TBHP and

• 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

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• of 1-fluorobis(phenylsulfonyl)methane (FBSM) to α,β-unsaturated ketones with cinchona alkaloids [9]. Fluorinated Michael acceptors usually contain one fluorine atom or a trifluoromethyl group in the structure [10][11][12]. There are also known examples of gem-difluoroalkenes being used as Michael

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

• various substituents on the aromatic ring. Additionally, a variety of substituted esters, ketones, and nitriles were found to be compatible with the reaction. Additionally, the same approach was used for the aryl sulfonylation. Trisubstituted allylic sulfones 35 were synthesized by reacting MBH acetate 33

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• Jinbo Ke Pit van Bonn Carsten Bolm Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.20.235 Abstract We present a mechanochemical synthesis of difluoromethyl enol ethers. Utilizing an in situ generation of difluorocarbenes, ketones are

• by these findings, we now explored difluoromethylation reactions with compounds bearing less nucleophilic functional groups. Ketones caught our particular attention as they contain a weak nucleophilic carbonyl oxygen adjacent to an electrophilic carbonyl carbon. Previous studies have focused on

• sodium fluoride catalyst, with simple ketones, which resulted in the formation of difluoromethyl 2,2-difluorocyclopropyl ethers (Scheme 1B). Although the reactions worked well, it is also noteworthy that the use of TFDA as reagent, liberated fluoro(trimethyl)silane (TMSF), carbon dioxide, and ozone

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

• chlorides in the presence of a copper catalyst to afford the corresponding tetrafluoroethylenated ketones 19. The ketones were then condensed with (R)-1-phenylethylamine under the influence of TiCl4 [34][35] to prepare various optically active imines (R)-16 in high yields (Scheme 3). Based on the result of

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• ]. One study reported a reaction involving the asymmetric reduction of ketones using an achiral borane, denoted as B(p-HC6F4)3, paired with a chiral oxazoline, as depicted in Scheme 3 [28]. Remarkably, in this study, these FLPs demonstrated the capability to achieve high conversion rates and enantiomeric

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

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

• . For example, Liu and colleagues demonstrated the electrochemical oxidation of benzylic C–H bonds to ketones using tert-butyl hydroperoxide as the radical initiator [14]. This method was applied to functionalize bioactive molecules, with celestolide, ibuprofen methyl ester, and papaverine being

• > secondary. Functional groups such as silyloxy, amides, ethers, esters, enolizable ketones, and nitriles were found to be compatible with this transformation. Late-stage functionalization of different molecules was demonstrated; for example, the azidation of ibuprofen occurred preferentially at the secondary

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• usefulness for the epoxidation of the β-CF3-α,β-unsaturated ketones [40], we applied this method at first for the epoxidation of 1b. However, contrary to our anticipation, only a total recovery of the substrate was observed, and further search for an oxidant reached the usage of a NaClO aqueous solution with

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• ) [21] are known compounds and were prepared from the corresponding commercially available ketones by reaction with NaBH4 in EtOH or EtOH/THF 1:1. 1,1-Diphenylethanol (1i) is also a known compound and was prepared according to the reported procedure [29]. 9H-Fluoren-9-ol (1m) and triphenylmethanol (1n

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

• proved ineffective in facilitating the Michael addition of bisthiomalonates to conjugated ketones, whereas DABCO enabled the formation of desired products under mild conditions [30]. However, reports of highly stereoselective protocols utilizing hydrogen bonding catalysis have mainly focused on

• , condensation reactions, including the formation of transient C=N bonds, are significantly promoted under ball milling conditions [12][13][14]. It is noteworthy that the application of primary amines for activating cyclic ketones under mechanochemical conditions remains largely unexplored [36]. We aim to fill

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• (MCRs) are one-pot reactions that utilize three or more readily available starting materials [1][2][3][4]. Typically, MCRs use reactive functional groups such as ketones or aldehydes, carboxylic acids, amines, and isocyanides where these simple building blocks can be utilized to form large libraries of

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ketene dithioacetals [67] or β-ethylthio-β-indolyl-substituted α,β-unsaturated ketones [68], the cyclocondensation reaction of β-ethylthio-β-indolyl-substituted α,β-unsaturated ketones with hydrazines/hydroxylamine [69][70][71] and the tandem [5C + 1C/1N]-cycloaromatization of α-alkenoyl ketene

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• ) substituent in the meta-position [38][39][40][41][42][43]. For example, several methods based on the Michael condensation–oxidation sequence starting from α,β-unsaturated ketones have been described (Scheme 1B) [44][45][46][47][48][49][50]. Recently, several methods have been developed based on the