Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• . This can be obtained from renewable biomass and is therefore considered to be a "green" solvent. In 2-MeTHF (conditions (C)), product 1f was isolated with a yield of 95% and derivative 1h with a yield of 91%. This shows that the sustainable solvent is a potent alternative to 1,4-dioxane. With the new

• ® and purified by flash chromatography on silica gel (n-hexane/acetone 3:1). Then, the crude product was suspended in n-hexane, the supernatant separated by filtration and the precipitate was dried under vacuum to afford aroyl-S,N-ketene acetal 1i (1.78 g, 4.93 mmol, 99%) as a yellow solid. Mp 159 °C

• (lit. 155 °C [5]). 1H NMR (300 MHz, CDCl3) δ 5.24 (s, 2H), 6.43 (s, 1H), 6.92–7.04 (m, 3H), 7.09–7.16 (m, 3H), 7.19–7.29 (m, 4H), 7.57 (dd, 3J = 7.7 Hz, 4J = 1.3 Hz, 1H), 7.73–7.83 (m, 2H); MALDI–TOF–MS (m/z): 362.2, [C22H16FNOS + H]+. Retrosynthetic analysis of aroyl-S,N-ketene acetals 1 and tentative

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• ) salts, including halides, nitrate, tetrafluoroborate, or perchlorate, were much less effective or completely inert. Keywords: C–P coupling; copper; enol acetates; β-ketophosphonates; phosphorylation; Introduction The construction of C–P bonds is a highly important task in key areas of modern chemistry

• efficiency, strong basic or acidic conditions, and excess of organohalides as starting materials. Recent years have witnessed the upsurge of free-radical oxidative phosphorylation transformations that became a reliable strategy for the construction of C–P bonds in organophosphorus chemistry [2][32][33][34

• leading to β-ketophosphonates have been reported [41][42][43][44][45][46][47][48][49][50][61], challenges in this area still exist primely in the search for new available synthetic equivalents of alkynes and alkenes for effective radical C–P bond formation. Enol acetates are potentially versatile

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• thermogravimetric analysis (TGA) (Figure S703 in Supporting Information File 1). Temperatures at which weight loss reached 10% (T90) were 468–491 °C and carbonization yields at 900 °C (CY) were ca. 46 wt % for [4.3.3]_oligo and [4.3.3]_linear. T90 and CY of [4.3.3]_branch showed higher values of 543 °C and 75 wt

• % probably owing to the network structure. By contrast, soluble [3.3.3]_oligo and [3.3.3]_linear had relatively high T90 of 528–532 °C and CY of 68–76 wt %. The high values were ascribed to two unsubstituted naphthalene rings in precursor [3.3.3]_CH2OH, which caused facile branching in the reaction or

• heating process. T90 and CY of [3.3.3]_branch (415 °C and 64 wt %) were lower than those of [3.3.3]_linear because of two-step decay profile (Figure S703a in Supporting Information File 1). All the samples showed broad powder X-ray diffraction (PXRD) patterns with unclear peaks at around 2θ = 11° and 20

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• Julius Seumer Nicolai Ree Jan H. Jensen Department of Chemistry, University of Copenhagen, Copenhagen, Denmark 10.3762/bjoc.21.94 Abstract The mild and selective functionalization of carbon–hydrogen (C–H) bonds remains a pivotal challenge in organic synthesis, crucial for developing complex

• molecular architectures in pharmaceuticals, polymers, and agrochemicals. Despite advancements in directing group (DG) methodologies and computational approaches, predicting accurate regioselectivity in C–H activation poses significant difficulties due to the diversity and complexity of organic compounds

• . This study introduces a novel quantum mechanics-based computational workflow tailored for the regioselective prediction of C–H activation in the presence of DGs. Utilizing (semi-empirical) quantum calculations hierarchically, the workflow efficiently predicts outcomes by considering concerted

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• compounds [18]. Presented in this paper is a new synthetic route involving GBB, N-acylation and IMDA reactions for making intermediate III followed by dehydrative re-aromatization to give imidazopyridine-fused isoquinolinones C (Scheme 1C). Results and Discussion Following the reported procedures [10], the

• initial GBB reaction of aminopyridines 1 (0.5 mmol), isocyanides 3 (1.2 equiv), and furfuraldehydes 2 (1.2 equiv) was conducted in 3:1 CH2Cl2/MeOH (4 mL) using Yb(OTf)3 (0.08 equiv) as a Lewis acid catalyst under microwave irradiation at 100 °C for 1 h (Scheme 2). Nineteen distinct adducts 4 were obtained

• in 1,2-dichlorobenzene at 180 °C for 4 h, which gave 8a in 85% conversion and 82% isolated yield (Table 1, entry 3). Other solvents like toluene and xylene gave minimal or no product. Different combinations of temperature and reaction time couldn’t improve the yield. Among the various Lewis acids

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• macrolides with hydroxy groups at C20 or C7, identified as borrelidins C–E (Table 1, entries 4, 7, and 8) [19]. Borrelidins CR1 and CR2 (Table 1, entries 5 and 6), amide-containing congeners, were also isolated through bioassay-guided fractionation and purification of marine microorganisms from Costa Rica

• these sulfones with epoxides 23b and 23a, respectively. Following the literature procedure for a similar reaction, using n-butyllithium in the presence of BF3·Et2O at −78 °C, the coupling reaction unfortunately resulted in the decomposition of the reactants (Scheme 4). The authors hypothesized that the

• epoxides 23b and 23a with the non-protected variant 23c, and reacting it with sulfone 27 after pre-complexation with Ti(OiPr)4, again led only to decomposition. Given the unsatisfying results, Uguen and co-workers replaced the epoxides 23a–c to monoethers 46a and 46b, derived from trans-2,3-epoxy-1,4

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• HMBC spectrum of 2 allowed unambiguous assignment of the amine substitution at C-8 with the amine proton (δH 8.30) showing strong HMBC correlations into the triazolopyrazine scaffold [δC 147.9 (C-8), 139.7 (C-9)]. 2D NMR correlations used to characterise the structure of 2 are shown in Figure 2, along

• General experimental Melting points were measured using a Cole-Parmer (Chicago, IL, USA) melting point apparatus and were uncorrected. UV spectra were recorded using an Ocean Optics (USB-ISS-UV/VIS) spectrophotometer. NMR spectra were recorded at 25 °C on a Bruker (Billerica, MA, USA) AVANCE III™ HD 500

• synchronisation, as previously described [16]. Puromycin, chloroquine, pyrimethamine, and dihydroartemisinin were used as reference compounds. Following incubation of assay plates for 72 h at 37 °C, and 5% CO2 and 5% O2, parasites were stained with 2-(4-amidinophenyl)-1H-indole-6-carboxamidine (DAPI) and imaged

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• and ratio of α-CD that was added to the salt solution [40]. Studies at different temperature values demonstrated that the precipitate is less soluble as the temperature decreased and thus the gold extraction was optimal at 0 °C. Tests with excess stoichiometries of α-CD (2:1, 3:1, 4:1, 5:1) showed

• -precipitation yields from aqueous solutions of α-CD (20 mM) and MAuBr4 (10 mM) (M = Na/K/Rb/Cs) measured at 20 °C by UV–vis spectrophotometry. Right) Structures of the adducts present in co-precipitates with different alkali metals. Reproduced from Z. Liu et al. [40], “Cation-Dependent Gold Recovery with α

• (left) and the 2:1 (right) complexes, showing the positions of K+ cations and Au(CN)2− anions as well as the relative dispositions of the α-CD tori. Adapted with permission from [49], Liu, W.; Jones, L. O.; Wu, H.; Stern, C. L.; Sponenburg, R. A.; Schatz, G. C.; Stoddart, J. F. Supramolecular gold

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• acid (7-ACA) from cephalosporin C by cephalosporin C acylase [37], was used as a chiral starting material. After esterification of both carboxylic acid functions followed by cyclization to the lactam [38][39], the six-membered ring structure was established as (R)-methyl 6-oxopipecolate (7) with a high

• product 4 (Scheme 5a). The transformation of the enamine had to be carried out by reduction of the N-acyliminium ion by NaBH3CN in the presence of TFA, as Pd/C with H2 would lead also to the reduction of the triple bond. The products (2R,6S)-13 and (2R,6R)-13 were obtained in a 1:1 ratio (Scheme 5b

• given by switching one in an equatorial position. Using Pd/C and H2 for hydrogenation reactions usually leads to reduction of double or triple bonds, while aromatic systems tend not to be affected [58]. However, 3m and 3p undergo hydrogenation in the aromatic moiety, while 3p displays a complete

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• 7.750 ppm (compound 1, proton b, Figure 3A) shifting upfield and the multiplet at 7.60 ppm (protons c and d, Figure 3A) shifting downfield and merging into a single multiplet when approximately 1:1 ratio of HIM to salt was added as shown in Figure 4. Additional titration data are provided in Supporting

• assembly with Buckminster fullerene. (C) This work: Association of Phe HIM with first group alkali metal cations. Secondary bonds are highlighted in red. Two conformations of the HIM were found. One conformation projected all three benzyl groups in a vertical arrangement I (bottom) while the second

• curcumscribe the small cyclic core represented by blue color. Three carbonyl amides project outward. B) DFT image of 1 displaying the distribution of Mulliken charges on iodine (purple), oxygen (red), and carbon (grey); benzyl groups are ommited for clarity. C) Calculated electrostatic potential map showing

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• derivatives were obtained under asymmetric catalysis with a Ni(II)–bisoxazoline complex [15] and a Nd(OTf)3/N,N'-dioxide/LiNTf2 delay catalytic system [16], respectively (Scheme 1b and c). However, further exploration for convenient asymmetric catalytic synthetic methods is still in demand because the former

• The reaction of diethyl 3-phenyl-1-(4-toluenesulfonyl)aziridine-2,2-dicarboxylate (1a) and benzaldehyde (2a) was first selected as a model reaction to optimize the reaction conditions (Table 1). When aziridine 1a (0.2 mmol) and aldehyde 2a (0.3 mmol) in dried toluene (1 mL) were stirred at 10 °C for

• time. The yield was improved from 21% to 29% to 34% with similar enantio- and diastereoselectivities at 25 °C, 45 °C, and 55 °C, respectively, but the enantioselectivity decreased slightly at 55 °C (Table 1, entries 15–17). Further extending the reaction time to 48 h at 55 °C, resulted in an increased

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

• cinnamic acid. For example, Chen and co-workers (2020) reported the Pd-catalyzed N-acylation of cinnamic acids using tertiary amines to generate the corresponding amides 83 and 84 in good yields via C–N cleavage (Scheme 25) [61]. The active Pd0 species was inserted into the carboxylate group to afford the

• yield. The reaction proceeds via a CeO2-coordinated carboxylate mode (Scheme 31A) [67]. In addition, the catalyst also offered high reusability for up to 4 runs thus further promoting the eco-friendliness. Carbonyl activation via Lewis acid–O=C interaction has also been achieved using other transition

• cinnamic acid (7) to give amide 12 in excellent yield via Ti(IV)–O=C complex 102 (Scheme 31C) [69]. 2.1.3 Photocatalysis: Photoredox catalysis has gained much attention as a sustainable alternative approach to performing O/N-acylation by utilizing light as a renewable source. For example, Li and co-workers

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• carbon nanomaterials category in view of their stability, water affinity/dispersibility, and low toxicity [1][2][3][4]. Such nanomaterials significantly absorb in the 280–350 nm region due to a wide range of π–π* (C=C) and n–π* (C=O) transitions in both the core and on the surface of the particles. CDs

• photooxidant or photoreductant in the presence of a suitable electron donor or acceptor [18], and these properties have been exploited in procedures for the formation of both C–C and C–heteroatom bonds [18][19]. Our research groups recently focused on the application of CDs in light-mediated organic synthesis

• from direct photoreactivity [24][25], sulfonium salts can be easily reduced under photoredox-catalyzed conditions [20][21][22], and the resulting radical undergoes homolytic cleavage of one of the C–S bonds, releasing an aryl radical Ar• and a diaryl sulfide Ar2S. Subsequently, triarylsulfonium ions

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• ligands with axial chirality for Pd-catalyzed asymmetric allylic substitution reactions. For example, the Zhou group reported a P,olefin-type chiral ligand 3 with C–C bond axial chirality for this reaction (Figure 2) [27]. Additionally, we have recently reported chiral ligands with C–N bond axial

• detector and found that the C(aryl)–N(amide) bond axial chirality exists in amide compound 7. We attempted the optical resolution of racemic compound (±)-7 and obtained (+)-7 and (−)-7 using a semi-preparative chiral HPLC on 50 milligram scales. We also investigated the racemization process associated with

• the axial chirality of compound 7 (see Supporting Information File 1). The racemization barrier (ΔG‡rac) of (−)-7 in n-dodecane was determined to be 25.0 kcal/mol at 25 °C, as calculated using the Arrhenius and Eyring equations [33][34][35]. Therefore, the half-life of racemization of ligand (−)-7 at

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• Abstract A variety of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones were prepared by a combination of Sonogashira reaction and subsequent cyclization by domino C–N coupling/hydroamination reaction. The optical properties (UV–vis absorption and fluorescence) depend on the substitution pattern of the compounds

• instance, deazapurines represent heterocyclic fused pyrimidine bases which have found special attention, due to their widespread occurrence in natural alkaloids exhibiting various biological properties. For example, cadeguomycin (A), tubercidin (B), and toyocamycin (C) show antibiotic properties, while

• obtained for product 3e derived from 3-tolylacetylene. However, the yield for compound 3f dropped to 60% because of the more sterically hindered 2-tolylacetylene. The domino C–N cross-coupling/hydroamination reaction of 3a–h with various anilines was studied next (Scheme 2) [28][29]. The conditions were

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• aldol condensation of 5 provided the tetracyclic α,β-unsaturated enone 6 in 57% yield. Subsequent catalytic hydrogenation using Pd/C conditions delivered the hydrogen to the alkene from the less hindered face, producing ketone 7 with high diastereoselectivity. Final reduction of both the amide and

• the reduction of amide-generated ketone 12 after a subsequent Dess–Martin oxidation. Upon treatment of 12 with Co(acac)2 and PhSiH3 in iPrOH at 80 °C, the Mukaiyama hydration of enamide delivered hemiaminal 13. Despite the incorrect configuration of the newly formed hydroxy group, it is considered

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• Daniel Straub Markus Gross Mona E. Arnold Julia Zolg Alexander J. C. Kuehne OC III - Institute of Organic and Macromolecular Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany Center for Integrated Quantum Science and Technology, Ulm University, Albert-Einstein-Allee 11, 89081

• –LUMO energy gaps are identical and their respective transitions exhibit identical transition dipole moments [19][32][33]. For the |D1⟩ transition these two degenerate transitions mix in an out-of-phase fashion leading to the observed weak absorption at 544 nm (see Figure 1b and c). When looking at the

• Mulliken symmetry labels, one realizes that the |D1⟩ transition is in fact symmetry forbidden. By contrast, in-phase mixing of the transitions for the |D2⟩ transition leads to strong absorption at 374 nm, a transition that is symmetry allowed (see Figure 1b and c). In TTM, the ϕ is independent of the

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• , versatile key triflate intermediate 3, which allowed the introduction of substituents attached by a C–C bond to position 4 of the β-carboline scaffold by cross-coupling reactions. Sonogashira reaction of compound 3 with N-(3-butynyl)phthalimide (4) led to coupled compound 5. Cleavage of the phthalimide

• hydrogenation of the C=C double bond in the side chain gave brevicarine (2). The first total synthesis of brevicarine is shown in Scheme 3 [2][20][21]. Condensation of indole (11) with 1-methylpiperidone (12) gave compound 13 [22]. N-Alkylation of 13 with benzyl bromide, followed by treatment of the quaternary

• 21 under extremely harsh conditions (100 °C, 130 bar), followed by N-acetylation gave a mixture of diastereomeric racemates 22, which was cyclized to a diastereomeric mixture of β-carboline derivatives 23. Heating of 23 in pivalic acid in the presence of a catalytic amount of trifluoroacetic acid

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• equivalent of commercial iodomesitylene diacetate (CAS [33035-41-5]) and 1 equivalent of MsOH (Table 1, entry 4). Here, it was necessary to maintain a temperature of 0 °C, as vigorous bubbling and rapid decomposition occurred when the reaction was initiated at room temperature. In all cases (Table 1), only a

• steric bulk of the isopropyl group unfavorably affected the reaction outcome. However, we found that when 3 was subjected to the more active combination of iodomesitylene diacetate and p-TsOH·H2O at 0 °C in CH2Cl2, the desired product 4 formed in a much-improved yield of 57%. Not all tethers were

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• offers unique features, including twisted structures, reduced π–π stacking, and enhanced reverse intersystem crossing rates, becoming a better donor compared to fully planar compounds as carbazole (c). Similarly, 5H-dibenz[b,f]azepine (IMD, b) has been incorporated into D–A–D structures, showing

• interesting photophysical properties compared to common substrates like c, diphenylamine (d), and phenoxazine (e) [28][29][30]. However, their potential as D-unit in organic PCs remains unexplored. For this reason, studying this avenue could unlock new opportunities for the synthesis and design of more

• . Additionally, we aim to evaluate the unique effect of the TBA donor unit (a) compared to other donors. We next synthesized diverse D–A structures employing common nitrogen-based compounds widely used in materials chemistry like carbazole (c), diphenylamine (d), and phenoxazine (e). Furthermore, we wanted to

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• involving limonoids. Krishnolides A and C (7 and 8, respectively; Scheme 1A) were identified by Wu and co-workers from the seeds of a Krishna mangrove Xylocarpus moluccensis [26]. These two molecules belong to khayanolides, a class of rearranged phragmalin limonoids characterized by a structurally intricate

• tricyclo[4.2.110,30.11,4]decane ring system. Additionally, krishnolides A and C contain 9–11 stereogenic centers and exhibit diverse oxidation patterns. Their relative and absolute configurations were determined through NMR, HRESIMS and ECD experiments, as well as single crystal X-ray diffraction analysis

• convergent approach leveraging an AcOH-interrupted Nazarov cyclization to establish the [5,5,6,6]-tetracyclic scaffold with precise stereochemical fidelity. Results and Discussion Our retrosynthetic analysis toward krishnolides A (7) and C (8) is delineated in Scheme 1B. We hypothesized that these two

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• , propiolic acids 8a–d, and isocyanides 4a–e. By conducting the reactions in methanol at 70 °C, we obtained the desired Ugi adducts 15a–x in fair to good yields of 26–72% allowing for the variation of substituents across all components of the U4CR (Scheme 2). Notably, the Ugi reaction toward substrate 15a

• , when performed at room temperature, proceeded with lower efficiency compared to the reaction at 70 °C, leaving some of the starting 1H-pyrazole-3-carbaldehyde (14a) unreacted. Propargylamide 15a was selected as a model substrate to optimize the reaction conditions for the intramolecular

• by nitrogen nucleophiles [59][60]. When the reaction was conducted with 5 mol % of AgOTf in toluene at 80 °C for 20 hours, pyrazolo[1,5-a][1,4]diazepine 16a was obtained in 46% yield, while complete conversion of the starting material 15a was not achieved (Table 1, entry 1). Increasing the

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• , oxidative addition of the C–I bond to palladium formed the four-membered aryl–palladium complex Int-5. Steric hindrance from the bulky dppm ligand, combined with slower aryne release (using KF as the fluoride source), attenuated aryne coordination. Under these electron-deficient conditions, CO

• ensuring high regioselectivity. In 2018, the Jiang group developed a regiodivergent synthetic method for indolo[3,2-c]coumarins 10 and benzofuro[3,2-c]quinolinones 9 via controllable palladium(II)-catalyzed carbonylative cyclization (Scheme 3) [21]. When ligand L3 coordinates with the palladium center, the

• elimination yields the benzofuro[3,2-c]quinolinone product 9 along with a Pd(0) species, which is reoxidized to Pd(II) by BQ (benzoquinone). When the ligand is switched to the sterically bulky and electron-rich dppm, the chemoselectivity is reversed: the palladium center now preferentially coordinates with

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• reorganization likely involves the cleavage and re-formation of the dynamic Ctriazine–OAr bonds, and the presence of an excess of base could facilitate the formation of the thermodynamic-favored reorganized products [29][31]. The benzyl groups were subsequently removed under Pd/C and H2 conditions to afford the

• ) solution of the compound at 4 °C, enabling structural analysis of the ultracycle. As illustrated in Figure 1, the backbone of B4aH adopts a Z-like shape with a flexible conformation. The two oxacalix[2]arene[2]triazine subcavities are positioned along the short axis in a staggered face-to-face arrangement

• , while the glycol chains are oriented along the long axis in the opposite orientations. In packing mode, the submacrocycle units form close contacts through intermolecular hydrogen bonding, C–H···π, and lone pair–π interactions, resulting in a 1D linear assembly. Anion recognition With the functional

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• species A which is in equilibrium with the Cu–O enolate B [11]. In the presence of excess of LiOt-Bu, a salt metathesis reaction between this base and intermediate B generates lithium enolate C and LCuOt-Bu to close the copper catalytic cycle. The formation of a lithium enolate is consistent with the

• different diastereoselectivity observed when other bases featuring different metal cations were used (Table 1, entry 2 vs entry 5), and the absence of any significant stereochemical influence from the copper complex (Table 1, entries 9–14). Lithium enolate C would then undergo a diastereoselective conjugate

• details). In contrast, the use of CsF in dioxane at 70 °C proved to be efficient and selectively provided cyclopropane 9 in good yield, albeit with no diastereoselectivity (Table 2, entry 1). Cs2CO3 was also selective for this cyclization and provided a slight increase in diastereoselectivity, although