Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• rearrangement under mild conditions [6], and the Nazarov-type electrocyclization of alkenyl aryl carbinols [7]. Exploiting the ease with which calcium forms hydrides, hydrogenation of aldimines, transfer hydrogenation of alkenes, and even deuteration of benzene by an SNAr mechanism, have been recently achieved

• in elucidating the mechanism by which these bifunctional compounds act as powerful catalysts [21][22][23][24][25][26][27][28][29]. Since Ishihara disclosed the crucial role of calcium in many purportedly purely organocatalytic BINOL phosphate-catalyzed reactions [30][31], several asymmetric synthesis

• –BINOL phosphate complex as catalyst. Herein, we report the development of the first Ca–BINOL phosphate-catalyzed asymmetric hydrocyanation of hydrazones and the results from DFT calculations to elucidate the mechanism of this transformation. Results and Discussion We first set out to study the

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• , we conducted a 5.0 mmol scale reaction and obtained the target product 3aa in 82% yield (Scheme 3). Based on previous reports, a plausible mechanism was proposed. In the presence of a copper catalyst, aniline reacts with cyclobutanone oxime to form an imine intermediate, which undergoes isomerization

• spirotetrahydroquinoline (STHQ) scaffolds. Substrate scope. General reaction conditions: aniline 1 (0.2 mmol), 2 (0.4 mmol), and Cu(TFA)2 (0.04 mmol) in hexane (2.0 mmol) under air atmosphere, 12 h, 80 °C. Yields refer to isolated yields. Scale-up reaction.a Proposed mechanism. Optimization of reaction conditions.a

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• transfer, X-ray crystallographic analysis of the (tert-butyl)(adamantyl)Bpin·Li(THF)2 complex revealed that the B–(adamantyl) bond is shorter than the B–(tert-butyl) bond (1.673 vs 1.692 Å). DFT calculations further illuminated the underlying mechanism by comparing two distinct transition states: TS1

• transition states: an open transition state TS7 facilitated by LiOt-Bu and a closed transition state TS6 without base assistance (Scheme 17a). The significant energy difference between these pathways (ΔΔG‡ = 4.3 kcal/mol) strongly favors the open transition state TS7 mechanism, attributed to reduced steric

• interactions and enhanced electronic stabilization through lithium coordination. This explains the critical role of lithium in achieving a high enantioselectivity. Isotope-labeling experiments using 10B-enriched 1,1-diborylalkanes (S)-49 further supported this mechanism, showing a stereoinvertive

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• 9d-D. Furthermore, monoesters 9 are also prone to spontaneous decarboxylation upon storage. Therefore, freshly prepared material should be used in the electrolysis. Based on experimental evidence, a working mechanism for the formation of 2-aminoproline 6a is proposed (Figure 4). Accordingly, an

• mM concentration, respectively, in 5:1 MeCN/H2O (0.1 M Et4N–BF4). B) Anodic oxidation of pyrrolidine 6a. Plausible mechanism for formation of pyrrolidine 6a and hemiaminal 10a. Preparation of malonic acid monoester 9a. Electrolysis of acid 9d in deuterated solvents. Scope of the decarboxylative

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• a photoredox reaction, whereas when embedded within the protein, the Ru-based ArM complex promoted histidine modification through an energy-transfer mechanism (Figure 5). Based on DFT calculations, this is permitted by the modification of the energy diagram of the ruthenium complex in the presence

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

• ). Additionally, the Tiwari group developed a metal-free protocol using only K2S2O8 as an oxidant for the activation of DMSO to MMS (Scheme 8, path II) [38]. Under these conditions, an alternative mechanism arises in which the imine intermediate B, formed as previously stated through reaction between the aniline

• , 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

• derivatives are isolated as side-products. Interestingly, when Liu et al. [40] modified this reaction by using a copper(II) catalyst under aerobic oxidative conditions, the regioisomers III (2-arylquinolines) were obtained (Scheme 9). To rationalize this singular result, the authors proposed a mechanism in

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

• established by X-ray analysis. The proposed mechanism of the considered processes is outlined at Scheme 8. Initially, the free nitrogen nucleophile is reversibly generated from the corresponding hydrochloride or acetate. Next, acid-catalyzed addition of the amine component to the carbon atom of the aroyl

• conditions: 1c (1 mmol, 0.30 g), hydroxylamine hydrochloride (1.2 mmol, 0.08 g), EtOH (5 mL). Proposed reaction mechanism. Synthesis of product 13. Reaction conditions: 8o (1 mmol, 0.37 g), pivaloyl chloride (3 mmol, 0.36 g), MeCN (5 mL). Optimization of the reaction conditionsa. Supporting Information

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

• present reaction, and products 17l and 17m were isolated in high yields with moderate to high stereoselectivities. The plausible reaction mechanism is shown in Figure 3. First, the removal of the acidic proton of the pre-nucleophile by potassium carbonate to form intermediate I, which undergoes cation

• -amino cyanoesters with contiguous tetrasubstituted carbon stereogenic centers by the catalytic Mannich reaction. Further investigations into the reaction mechanism and product applications are ongoing in our group. Selected examples and applications of chiral halogen-bonding catalysts. Selected examples

• for the construction of contiguous tetrasubstituted carbon centers via the Mannich reaction and this work. Plausible reaction mechanism. Catalyst screening for the asymmetric Mannich reaction. All yields were determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. N

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

• . Considering the high diastereoselectivity observed both in the presence and absence of the squaramide catalyst, we propose a plausible mechanism (Scheme 3) that involves hydrogen bonding activation of the methyl trifluoropyruvate by the NH₂ group of the aminopyrazole. This interaction directs the attack of

• chromatography. Diastereoisomeric ratio (dr) determined by 1H NMR of the crude reaction mixture. Plausible mechanism and X-ray structure of compound 5aca. Optimization of the reaction conditions.a Supporting Information Supporting Information File 14: Detailed experimental procedures, characterization data, and

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• suggest potential triplet-state formation, which is involved in the proposed mechanism for the cycloaddition reaction. Although Me4B could theoretically form triplet states, given its fluorescence quantum yield of 51.7–67.3%, its crystallographic structure is not conducive to this reaction, regardless of

• bimane (Figure 7). The hypsochromic shift in this reaction means that provided correct irradiation wavelength is used, a 100% yield of the dimer could theoretically be achieved. Tentative mechanism The observed reaction likely follows a five-step mechanism, as suggested by previous studies [29][30]. The

• diradical. This triplet diradical undergoes another ISC, returning to the singlet state, which then forms a second single bond (Figure 8). This mechanism, involving both singlet-excited states and triplet states via ISC, is consistent with the relatively low fluorescence quantum yields observed for Cl2B

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• the overall oxidation of 4a to 1a likely is a two-electron process, suggesting that the second oxidation step may involve disproportionation of putative Br(II) species (see Scheme 3D). Based on the control experiments described above we propose a plausible mechanism as shown in Scheme 3D. The reaction

• improving the substrate scope and understanding the reaction mechanism are in progress in our laboratory. Synthesis of cyclic diarylbromonium compounds. Substrate scope. Reactions were performed on a 0.15 mmol scale. Yields were determined by 1H NMR spectroscopy of the reaction mixture using 1,2,3,4

• : Representative jp vs v0.5 slope values for oxidation of Martin’s bromane precursor 6 (ref. [17]). D: Plausible reaction mechanism. Optimization of electrochemical oxidation/cyclization conditions.a Supporting Information Crystallographic data for the structure reported in this paper have been deposited with the

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• a coordinated mechanism. Noteworthy, the primary kinetic product of the cycloaddition reaction 5 is not transformed into the thermodynamic product 6 via a H-shift at the last stage. The expected aromatization with the formation of a furan ring, as happens in similar reactions, does not occur (Scheme

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

• , enthalpically stabilizing the rate-limiting attack of alcohol by 7.3 kcal/mol. The highly ordered transition state in this example, thought to prevent charge buildup through a concerted/synchronous proton-transfer mechanism between bifunctional acid units, highlights a key design criteria differing from the

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

• <1% impurity based on 1H NMR and MS analysis. The mechanism by which glutarimide displacement competes with SNAr merits some discussion. Thalidomide is well known for its configurational instability and racemizes rapidly [8]. However, equally important but much less appreciated is its hydrolytic

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

• temperature or the activation entropy, hydrogen bonding, solvent [24], nature of the leaving groups and the promoter used [25]. The mechanism of glycosylation reactions has long been categorised mostly as dissociative SN1 reactions proceeding through stabilised oxocarbenium ions with the role of counterions

• ignored [26][27][28]. However, recent experimental, kinetic, and physical data reveal the incidence of more associative mechanisms [29][30][31] wherein the mechanistic pathway of glycosylation seems to lie at an interface of SN1–SN2 reaction (Scheme 1) [29]. The continuum mechanism expands in two

• the extremes of SN1 and SN2 pathway by employing the effect of counter ions, showing close resemblance with the SNi mechanism [41], conforming to the famous Winstein’s ion-pair theory [42] and draws analogy with chlorination of alcohols by thionyl chloride [43]. Incorporating the role of counter ion

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

• excess of quinone 3 leads to the formation of 2-(indolin-2-yl)-4,5,6,7-tetrachloro-1,3-tropolones 8a,b as final products. The detailed reaction mechanism in acetic acid solution was studied by the PBE0/6-311+G(d,p) method on the example of the interaction of 2-methylquinolines and 2-methylbenzazoles with

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

• . who employed a ruthenium(II) complex 1 activated through photoinduced electron transfer. The latter is pre-activated by the osmium complex shown in Scheme 1 after irradiation in the red region [18]. According to the mechanism proposed by the authors, the reaction is facilitated when conducted in

• ). The mechanism of the reaction presented by the authors involves two different catalytic cycles as presented in Scheme 3c. After excitation of the osmium complex 13, this latter is reduced via the use of a tertiary amine to give the active species 14 able to oxidize the formed nickel complex 15 in the

• suppress side reactions. The cross-dehydrogenative coupling reactions, under near-infrared irradiation, was found to proceed via an energy-transfer mechanism involving singlet oxygen generation rather than the typical electron-transfer pathway observed in the presented visible-light-mediated reactions in

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

• has an E,E,E-configuration, while the compound 8a has a Z,E,E-configuration. On the basis of the above experiments and the previously published results [42][43][44][45][46][47][48][49][50][51][52], a plausible reaction mechanism was proposed in Scheme 4 to explain the formation of the various oxindole

• ), CH3CN (5.0 mL), rt, 2 h; yields refer to isolated yields. Proposed reaction mechanism for the various compounds. Optimization of reaction conditions.a Dimerization of MBH carbonates of isatins.a Supporting Information The crystallographic data of compounds 5a (CCDC 2390713), 5j (CCDC 2390714), 6e (CCDC

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

• compounds 8 and 9, we could show that when the reaction was carried out in the absence of ʟ-proline, the conversion of the starting CH acid 1 after 5 days was less than 50%, and the main products present in the mixture were compounds 2 and 3. The proposed mechanism for the formation of compounds 8 and 9

• participation. Interaction of diketone 1 with formaldehyde under the diffusion mixing conditions. Products of three-component reactions of methylene derivatives, formaldehyde and various dienes. Proposed mechanism for the formation of compounds 8 and 9 in the presence of ʟ-proline. Interconversion of

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• be isolated in 82% yield. Several control experiments were performed to investigate the possible mechanism of the reaction (Scheme 5). In Table 1, entry 17, no disulfide product was formed at 80 °C, however, an 85% yield of thiosulfonate was observed. This indicated that thiosulfonate could be an

• whether the reaction proceeded through a free radical mechanism, different free radical inhibitors were added to the reaction (reaction 7, Scheme 5). The addition of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) resulted in complete inhibition of the reaction, while BHT (2,6-di-tert-butyl-4-methylphenol

• ) exhibited a lesser effect. Considering that TEMPO, as an oxidizing agent, affected the reaction, it could be concluded that the reaction did not proceed through a free radical mechanism. Based on the results of the control experiments and the related literature [26][30][41][52], a possible mechanism for the

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• demonstrates the versatility of our methodology and its potential for further exploration in diverse chemical spaces. To gain a deeper understanding of the mechanism behind the observed reaction, we conducted a series of control experiments as outlined in Scheme 3a. Initially, we performed the model reaction

• mixture, which significantly impeded the progress of the desired reaction. Therefore, on the basis of the above experimental results and previous reports [21][27][28][29][30], we proposed a possible reaction mechanism (Scheme 3b), taking CF2HCOOH as the illustrative example. Initially, a double ligand

• . Reaction conditions: 1 (0.2 mmol), 2 (1.4 mmol), and PIDA (0.8 mmol) in solvent (2 mL) irradiated with 72 W white LEDs at room temperature for 12 h under a N2 atmosphere. Yields refer to isolated yield. aα,α-Difluorobenzeneacetic acid (2 equiv) was used. Control experiments and plausible mechanism

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• the desired thienopyrimidones 5a–e, quinolinopyrimidones 6a–e and indolopyrimidones 7a–e, respectively, as reported in the literature [42][44]. In accordance with the reported mechanism, after the initial formylation of the amino group at position 2, an intramolecular nucleophilic attack by the NH

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• theory (DFT) calculations, a proposed reaction mechanism is suggested as shown in Figure 3. Initially, copper acetylide INT-11 is formed by the reaction of acetylene with a copper precatalyst, leading to the formation of an N-acyl nitrene acetylide intermediate INT-12 after the incorporation of

• late-stage functionalizations of complex scaffolds such as peptides, drug molecules, and natural products containing unprotected free OH and NH groups are anticipated. Proposed reaction pathway for the copper-catalyzed synthesis of δ-lactams from dioxazolones. Proposed reaction mechanism for the copper

• -catalyzed synthesis of 1,2,4-triazole analogues from dioxazolones and N-iminoquinolinium ylides. Proposed reaction mechanism for the copper(I)-catalyzed synthesis of N-acyl amidines. Proposed reaction pathway for the copper-mediated synthesis of N-arylamides from dioxazolones. Proposed reaction pathway for

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

• decreasing the oxidation potential. A range of functional groups, such as halides, ethers, and heterocycles, were tolerated well, yielding the corresponding enantioenriched products 14 with high enantioselectivity in the presence of chiral bisoxazoline ligand L2. A possible mechanism is depicted in Figure 5

• enantioenriched nitrile products 29. The proposed mechanism is illustrated in Figure 8. [Mes-Acr-Ph]+* is generated through the photoexcitation of the photocatalyst [Mes-Acr-Ph]+, which undergoes electron transfer to the heteroarene 28, resulting in the formation of the [Mes-Acr-Ph]• and heteroarene radical

• standard Cu-catalyzed electrochemical protocol. Based on mechanistic studies, the proposed mechanism is shown in Figure 9. First, hydroquinone 34 is oxidized at the anode to generate a quinone intermediate 38. Meanwhile, the chiral copper catalyst reacts with the Schiff base 33, generating a nucleophilic

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• ]benzofuran (3fa) in 81% yield. Next, we explored the mechanism of the coupling reactions between 2-fluorobenzofurans 1 and arylboronic acids 2. Because these reactions proceed under mild conditions despite involving aromatic C–F bond activation [19], direct oxidative addition of C–F bonds is unlikely (Scheme

• , reductive elimination from G yields the coupling products 3. The following experiments were performed to elucidate the mechanism. Under the same conditions as the coupling reaction, stoichiometric amounts of Ni(cod)2, PCy3, and cod were treated with fluoronaphthofuran 1b at room temperature for 13 h