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

• containing a PH bond adds to the C=N bond of a preformed imine 30, while in the three-component Kabachnik–Fields reaction, the imine, which is generated in situ from a carbonyl compound and an amine, reacts with the dialkyl phosphite to produce the desired α-aminophosphonates 32 (Scheme 25) [72][74]. This

• phosphites can also undergo an addition to the C=O bond of the carbonyl component (Abramov reaction) giving α-hydroxy phosphonates 33 as byproducts (Scheme 26a) [72]. Competition between the two nucleophiles for the electrophilic carbonyl compound depends on their relative reactivity [74][77] and this lack

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• pyrrolones such interaction can lead to pyridazinone systems [10][11]. Despite on the plenty of reactions with nitrogen-containing nucleophiles there is only one example of recyclization using furanone with a carbonyl group at position 3 (Scheme 1a, previous work) [6]. However, no work on this type of

• intramolecular hydrogen bond between the NH-unit and the carbonyl group. The presented results indicate that the reaction of the aliphatic amine doesn’t lead to recyclization of the studied heterocyclic system. Further, we hypothesized that synthesis of the enamine 4a can be realized in one-pot variant without

• an electron-donating group in the aroyl fragment deactivates the carbonyl moiety and as a consequence blocks the considered process. In this case only stable salt 3b was obtained at reflux in AcOH for 24 h with 90% yield (Scheme 2c). At the same time, various aliphatic amines can be applied in the

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

• -workers developed chiral amine 1 with an electron-deficient iodine atom, which catalyzed the Mannich reaction in excellent yields and enantioselectivities [17]. In 2020, Huber and co-workers reported the bis(iodoimidazolium) 2-catalyzed Mukaiyama–aldol reaction of carbonyl compounds with enol silyl ethers

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

• properties along a C=C double bond [1]. This effect has been established to be very advantageous to expand the range of reactions of different functional groups that can be coupled efficiently through a conjugated π-system. In this context, the addition reaction of vinylogous nucleophiles to carbonyl

• compounds is a significant and important reaction for the selective synthesis of homoallylic alcohols in an efficient and sustainable way [2][3]. As carbonyl compounds, alkyl trifluoropyruvates [4][5] are an interesting class of compounds that have been used in addition reactions of different nucleophiles

• 12 in Table 1. With the optimized reaction conditions in hand, the scope of the vinylogous addition reaction of 4-alkenyl-5-aminopyrazoles 3 to alkyl trifluoropyruvates 4 was studied (Scheme 2). First, we evaluated the influence of the alkyl group in carbonyl compound 4, where we observed similar

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• exposing fresh material to light. In 2016, König and co-workers exploited rod milling to develop a photomechanochemical approach for the riboflavin tetraacetate (RFTA)-catalyzed photocatalytic oxidation of alcohols to the corresponding carbonyl compounds upon irradiation with five LEDs (λ = 455 nm) [69

• benefits of the photomechanochemical approach in the field of synthesis [77]. Specifically, they developed photomechanochemical conditions for the atom-transfer-radical addition (ATRA) of sulfonyl chlorides to alkenes, pinacol coupling of carbonyl compounds, decarboxylative acylation, and photocatalyzed [2

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

• carbonyl oriented outward (designated by “0” or “O”) and amide carbonyl oriented inward (designated by “1” or “I”). There are 64 (26) permutations of carbonyl orientations in our cages, of which 13 are unique for cage 1 after grouping by symmetry (and ignoring enantiomers), which we have labelled as C1–C13

• permutations of amide conformations. Cages 1–4 have cavity heights rCC that change with carbonyl orientation (“macroflexibility”). Additionally, cavity heights can change within a conformation due to cage axial twisting (“microflexibility”). For cage 1, crystal structures have been measured for the more stable

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• also be explained by C4 being located near the node of the LUMO. However, SNAr is still favored over glutarimide displacement potentially because the negative charge in the corresponding intermediate is stabilized by an extended conjugation system. In contrast, the negative charge in the carbonyl

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• atom economy, it significantly reduces the chance of migration as observed for acetyl groups. Various studies have revealed its dependence on both electron-withdrawing substituents and steric bulk on the carbonyl group [80]. It demonstrates that its migration rate is significantly increased by more

• electron-withdrawing substituents which also increase the electrophilicity of the carbonyl group. Again, more steric bulk in proximity to the carbonyl group, like in the benzoyl substituent, significantly reduces its migration property [81][82]. Hence, an increasing number of glycochemists across the world

• the C-2 position also contribute to the concept of ‘armed–disarmed’ glycosylation wherein C-2 ether-protected ‘armed’ thioglycosides were selectively activated over C-2 ester-protected ‘disarmed’ thioglycosides owing to the electron-withdrawing attribute of the ester carbonyl functionality [93

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• methylene at 67.7–68.0 ppm, one N-methyl at 38.1–38.2 ppm, and one carbonyl carbon signal at 166.5–167.6 ppm. Also for compounds 7i–n, distinct 13C NMR chemical shifts were observed: two methylene carbon resonances at 54.7–68.2 ppm, one N-methyl at 37.9–38.0 ppm, and two carbonyl carbon signals at 165.2

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• . In turn, in the IR spectra (KBr) of compounds 7a–f, absorption bands of the ester fragment in the region of 1714–1750 cm−1 and absorption bands of the carbonyl group of the amide fragment in the region of 1674–1688 cm−1 are observed, which suggests the existence of these compounds in the solid phase

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

• . These groups are distinguished by their terminal structures, which can range from heterocyclic to non-heterocyclic rings or even amino and carbonyl groups. Furthermore, cyanins can also be classified by the number of methine units in their polymethine chains, including monomethin, trimethin, pentamethin

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

• have made them to become valuable building blocks in organic synthesis. Nucleophilic additions or spiroannulation of the highly reactive carbonyl group at the C-3 position of isatins have various fascinating applications in organic synthesis, which allowed transformation of isatins into various

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

• adducts of formaldehyde condensation are formed under milder conditions and are highly reactive, which is important for further synthetic transformations. However, due to the high carbonyl reactivity of formaldehyde, its interaction with active methylene compounds is often complicated by polycondensation

• various CH acid derivatives and conjugated dienes (cyclopentadiene, 1,3-cyclohexadiene, 2,3-dimethylbutadiene and isoprene), leading to [4 + 2]-cycloaddition adducts (Scheme 1). It should be noted that in previous works describing three-component reactions of carbonyl compounds, conjugated dienes and

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• amide macrocycle with six aromatic residues (hereafter called cyclo[6]aramide for brevity, Scheme 1a) could mediate dimerization as a host. That is because such a 2D macrocycle has six carbonyl oxygen atoms pointing inwards as binding sites, demonstrating excellent affinity for cationic organic guests

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• identical racemic carbonyl nucleophiles to generate Cu-enolate 44 and Ni-enolate 43 simultaneously (Figure 10). The Ni-enolate 43 undergoes anodic oxidation through single-electron transfer, releasing nickel-bound α-carbonyl radical 45, whereas the copper complex 44 remains electrochemically inert under

• standard conditions. Subsequently, radical-polar coupling between electrophilic Ni-bound α-carbonyl radical intermediate 45 and remaining nucleophilic Cu-enolate 44 provides a chiral product 42 containing vicinal quaternary stereocenters with high stereoselectivity, and all three possible stereoisomers of

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

• some cases, activation of a carbonyl group by the copper catalyst to facilitate nucleophilic attack has also been reported. Moreover, both activations can be operative simultaneously. Since copper shows affinity either for multiple C–C bonds or polar functional groups, it seems the ideal tool for this

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

• process was inspired by the biocatalytic synthesis of aromatic polyketides by polyketide synthase from poly β-carbonyl substrates. Pyrrolidine-based organocatalyst C4 was able to promote a twofold atroposelective arene-forming 6-enolendo aldol condensation (Scheme 4). Sparr also realized a central-to

• yields and enantiomeric purities. The reaction was initiated by the formation of acylazolium intermediate Int-24 that underwent a 1,6-addition with the enol form of the carbonyl substrate to give Int-25. Cyclization was realized via an intramolecular aldol reaction to Int-26 (Scheme 15). Ye and co

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• starting material unreacted or resulted in complex mixtures, from which cyclodehydrogenation products, such as compound 7 (Scheme 1b), could not be isolated in a pure form. This can be attributed to the electron-withdrawing carbonyl groups, which make compound 1 unreactive to oxidation. For thionation of

• the carbonyl groups in 1, it was treated with three equivalents Lawesson's reagent, affording dithioketone 8a in a 40% yield together with trithioketone 8b in a yield of 10%. To expand the π-skeleton of 1, compound 8a was subjected to the Barton–Kellogg reaction with diazo compound 9, which was

• in the reported crystal structure of 1·CH2Cl2 [22]. The side view of compound 1 indicates that two of its carbonyl groups are oriented upwards while the third one points downwards. Compound 1 comprises three [5]helicenoid moieties, each containing three benzene rings and two seven-membered rings. In

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

• cyclic derivatives. Conjugated imines are usually synthesized from the corresponding carbonyl precursors by reaction with a sulfonamide in the presence of Lewis acids and a dehydrating agent such as molecular sieves [3]. Also, recently a palladium-catalyzed dehydrogenation of aliphatic imines was

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• existence of a substituted benzenoid chromophore was suggested by the UV absorption maximum at 258 nm. The presence of hydroxy and/or amino groups and a carbonyl group was indicated by IR absorptions at 3337 cm−1 and 1671 cm−1, respectively. The analysis of the HSQC spectrum, along with the 1H and 13C NMR

• ]. Despite the absence of an HMBC correlation directly indicating a connection between C-8 and C-9, the HMBC correlation between the N-methylene protons H2-10 (δH 3.66) and the carbonyl carbon C-9 (δC 161.5), along with the molecular formula of compound 1 by process of elimination, suggested that C-8 and 9-N

• were linked via a carbonyl group at C-9. Therefore, the gross structure of 1 was elucidated. The absolute configuration of ceratinadin G (1) was assigned by comparing its NMR and ECD data with those of psammaplysin F (2), whose absolute configuration has already been established [10][11][12]. The NMR

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• protons indicating the presence of a symmetrical aromatic moiety, were observed. The 13C NMR (Table 1) spectrum of 4 showed two carbonyls (δC 164.4, 173.9), with the carbonyl at δC 164.4 readily assigned to an acrylamide group, which is present in all previously published ianthelliformisamine molecules [7

• 3.33, 1.91, 2.21), and a three-bond HMBC correlation from δH 3.33, and a two-bond correlation from δH 2.20 to the carbonyl resonating at δC 173.9 [15]. The observation of a 3JCH correlation from δH 3.20 to the nitrogen-bearing carbon at δC 46.4 and to δC 173.9 supported the assignment of the

• ]. The 13C NMR (Table 1) data of 5 displayed six aliphatic carbons (δC 35.9, 26.1, 44.8, 46.3, 21.1, 30.4) and two carbonyl signals (δC 164.9, 173.6). Similarly to the other ianthelliformisamines, the aromatic (δC 131.6) and olefin (δC 124.5, 135.2) carbons were observed [7]. COSY correlations associated

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

• their amides, esters, and azides by FeCl2-catalyzed isomerization of 3-aryl-5-chloroisoxazole-4-carbonyl chlorides into 3-aryl-2H-azirine-2,2-dicarbonyl dichlorides followed by their reaction with nucleophiles are reported. Two approaches to the preparation of 3-aryl-5-chloroisoxazole-4-carbonyl

• derivatives [1]. In particular, the catalytic isomerization of 5-chloroisoxazoles allows the generation of azirine-2-carbonyl chlorides, which can be easily converted into a variety of azirine-2-carboxylic acid derivatives by reactions with nucleophilic reagents. Using this approach, numerous 2-(1H-pyrazol-1

• -ylcarbonyl)-2H-azirines, 1-(2H-azirine-2-carbonyl)benzotriazoles, 2H-azirine-2-carbonyl azides, anhydrides, amides, esters, and thioesters of azirine carboxylic acids, as well as azirine carboxylic acids themselves, have been prepared over the last decade (see [2] and references therein). Azirine-2

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• the ethyl or ethoxy groups and therefore it is very attractive for applications in medicinal chemistry and related areas [10][11][12][13]. α-Carbonyl sulfoxonium ylides are well recognized as more stable and more easily handled surrogates of diazo compounds [14][15]. They have also emerged as

• [28]. In 2017, the Aϊssa group described a procedure to better synthesize such α-alkyl-substituted carbonyl sulfoxonium ylides [29]. This protocol involved the alkylation of a dialkyl thioether, counterion exchange, oxidation, and eventual acylation (Scheme 1a). More recently, the Burtoloso group

• reported the α-alkylation of carbonyl sulfoxonium ylides via a Michael addition approach that occurred without any competition from cyclopropanation [30]. While this reaction represented the first direct alkylation of sulfoxonium ylides, it was nonetheless limited to the more reactive ester ylide variants

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

• a multicomponent reaction to obtain SIRT2 inhibitors (Scheme 12). The authors suggest a Knoevenagel condensation approach between isatin derivatives and ethyl cyanoacetate, followed by a Michael addition with C–H activated carbonyl compounds and intramolecular cyclization [50]. They synthesized 45

• carbonyl compound, and an isocyanide in a single operation. The reaction proved to be effective using different isocyanides, both aromatic and aliphatic ones. Additionally, the transformation worked with the convertible isocyanide. This opened the possibility of synthesizing various derivatives of racetams

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

• benzaldehydes, which may be attributable to that they have smaller steric demands in the vicinity of the carbonyl carbon atom than benzaldehyde. Importantly, we did not observe the corresponding homopropargylic alcohols [51] in all cases. Since this work is the first asymmetric catalysis study of isomerically