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

• a key intermediate product. This late-stage approach was previously described by us while utilising Suzuki–Miyaura or Sonogashira–Hagihara cross-coupling reactions to generate pipecolic acid derivatives with alkynyl substituents in the C6 position [35]. Here, we present a robust synthetic route to

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

• electron-withdrawing para-substituents generally gave the desired products 3ae and 3af in higher yields and enantioselectivities than aldehydes with electron-donating substituents (2b–d). Sterically congested 3-chlorobenzaldehyde (2g) and 2,6-dichlorobenzaldehyde (2h) produced the desired products 3ag and

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

• did not proceed, and (S)-13e was not produced. Likewise, no reaction occurred with a trifluoromethoxy-substituted derivative, resulting in no formation of (S)-13f. Reactions using isatin derivatives bearing halogen substituents at the 6-position proceeded efficiently, affording (S)-13g–i in good

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

• groups attached to the aniline, such as OMe, F, CF3, Me, and Br, were tolerated and did not greatly differ in terms of yield. With respect to substituents located at the alkynyl moiety, diminished yields were obtained for N,N-dimethylaminophenyl-substituted derivatives 4k and 4l and for m-tolyl

• -substituted compound 4h. No conversion was observed for starting materials 3g,h containing electron-withdrawing substituents located at the phenylacetylene moiety (products 4n,p). In addition, no conversion was observed for 3-methylaniline (product 4o). The photophysical properties of selected pyrrolo[3,2-d

• . Electron-donating N,N-dimethylaminophenyl substituents led to bathochromically shifted absorption and emission spectra accompanied by strongly elevated fluorescence quantum yields (up to 83%). Further studies will be devoted to the synthesis of novel polycyclic uracil derivatives with potential biological

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

• cyclization to form products in high yields and excellent enantioselectivities. Notably, only a single diastereomer was produced in each case. The single-crystal X-ray crystallography revealed a cis-configuration for both the alkene and ketone substituents on the enamide, indicating that the intramolecular

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

• triphenylmethyl radical [38][39]. In contrast to the Gomberg radical, the perchlorination prevents dimerization through the para-position. Moreover, the chlorine substituents in the ortho-positions twist the phenyl rings into a propeller conformation and out of the sp2-hybridization plane of the central methine

• radical unit. Now, the chlorine substituents screen the hemispheres above and below this plane, protecting the unpaired electron in the p-orbital from oxidation or other detrimental degradation. The weak emission of PTM with ϕ of 0.7% peaks at 609 nm (in tetrachloromethane (CCl4)) [40]. The racemic

• low ϕ (see Figure 2a) [50][51]. Perfluorinated triphenylmethyl radicals have been reported as well; however, neither UV–vis nor photoluminescence data are available [54]. Mixed perhalogenated triphenylmethyl radicals with fluorine, chlorine, and bromine substituents have been synthesized in an attempt

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

• , Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary 10.3762/bjoc.21.79 Abstract A new total synthesis of the β-carboline alkaloid brevicarine is disclosed. The synthesis was carried out starting from an aromatic triflate key intermediate, allowing the introduction of various substituents into

• , 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

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

• compatible with our optimized conditions (Table 2, poor performers). In many cases, complex mixtures of recovered starting material and multiple products were observed. Carbamate tethers with N-alkoxy substituents were essential for clean reactions; indeed, extensive decomposition was observed with N-ethyl

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

• substrates 15e–l was tested. The process proceeded efficiently in all cases, yielding pyrazolodiazepines 16e–l and demonstrating tolerance for various substituents on the aniline-derived aromatic fragment, including alkyl, halogens, electron-donating alkoxy groups, as well as electron-withdrawing

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

• different substituents and polysubstituted annular boronic acids 98, a Suzuki coupling was employed to synthesize advanced isoquinoline intermediates 100. Following this, a 6π electrocyclization reaction and nucleophilic reaction were developed to achieve C–C and C–N bond constructions, respectively

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

• introduction of lower-rim hydroxy substituents effectively enhances the dicarboxylate binding through cooperative hydrogen bonding and anion–π interactions. The selective recognition of long and flexible dicarboxylates holds exciting promise for the use of dicarboxylate sensors in medicine and industry. (a, b

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

• bearing aromatic and aliphatic substituents efficiently provided the allylboration product (Scheme 1a), the use of ester derivative 1 under same reaction conditions led to the formation of an unexpected product arising from the coupling of two dichloride molecules with no alkyne incorporation (Scheme 1b

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• demonstrated the efficient sensitization of an alkene-containing four boron substituents using Ir(ppy)3 as a suitable sensitizer in the presence of styrene, indicating a prominent role of the adjacent p-orbital [51]. While simple alkenylboronic esters have been employed as triplet diradical quenchers to

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• group, we investigated the reactions with various substituted 2-halobenzoic acids. The reactivity of 2-iodobenzoic acid derivatives (3a–d, 90−96% yields) was higher than that of 2-bromobenzoic acid derivatives (3a–d, 57−73% yields), the electronic properties of the substituents on the benzene ring had

• little effect on the reactivity. When the amidine substituent (R2) was changed to a cyclopropyl group, the yields of all reaction decreased, especially when substituents were present on the benzene ring (3e–h, 55−94% yields for 2-iodobenzoic acid, 43–76% yields for 2-bromobenzoic acid). We then

• reaction activity observed when substituents were presented on the benzene ring. Finally, we examined reactions with 2-halobenzoic acid derivatives where the R2 substituent was a phenyl group. In this case, the reactivity of 2-iodobenzoic acid derivatives (3m–p, 61–99% yields) was again superior to that of

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• relative position of the absorption bands in the azobenzene derivatives depends on the substitution pattern on the aromatic rings, which can act as a handle to affect the absorption properties of the compound class [3]. For instance, push–pull systems or the introduction of tetra-ortho substituents were

• studies on azobenzene [32][40]. Another interesting aspect, that could point to a more complex picture in the excited state landscape of these switches, is that the QYs of NAc-PAPs with R = NO2 and R = H are lower for the π→π* than for the n→π* transition, while for the other substituents the opposite was

• found. We thus suspect that the substituents play a crucial role in in the population of the respective exited state and we can at this state not rule out a contribution also from the triplet state. Moreover, we could not find a quantitative correlation between the R-substituents and ΦE→Z, however, some

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• ) has occurred at the exocyclic sp2-hybridized carbon atom, leading to the substitution of the 4-methoxybenzylamino group by a methylamino group. Therefore, the presence of substituents (electron-donating or electron-withdrawing groups) on the benzene rings attached to the 1- and 5-positions of the

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• from 88% to 99%. Similarly, chloro-substituted allene 1d exhibited good tolerance under these conditions, affording the corresponding nitrile 3d in an 88% yield, whereas phenethyl-substituted allene 1e provided 3e in a 95% yield. Allenes 1f–i featuring phenyl and alkyl substituents, including methyl

• , ethyl, phenethyl, and allyl groups, also underwent smooth cyanation, resulting in α-quaternary nitriles 3f–i in yields of 85–94%. Furthermore, aryl-substituted allenes 1j–o, incorporating electron-donating or electron-withdrawing substituents such as methyl, fluoro, chloro, bromo, trifluoromethyl, or

• . Trisubstituted allenes 1q–s bearing phenyl and dialkyl groups, including a cyclohexyl moiety, underwent selective cyanation to deliver the (E)-isomers of the corresponding nitriles 3q–s in yields of 90–95%. In addition, aryl- and dialkyl-substituted allenes 1t–x containing substituents, such as fluoro, chloro

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• tendency for hydro-dehalogenation. Tetrabutylammonium halide was chosen as the electrolyte due to its lower hygroscopicity and reduced tendency for reductive homocoupling of 4-bromobenzotrifluoride. In the presence of chlorinated substituents, neither the double coupling product nor the hydro

• -dechlorination product was observed. This notable result suggests performing a second coupling using conventional chemical methods, such as the Suzuki–Miyaura reaction. Furthermore, the coupling yield decreased for phenyl bromides bearing bulky ortho-substituents while hydrodehalogenation byproducts formed. The

• presence of air, no product was formed. This finding indicates that iodide salt plays a crucial role in driving the reaction and acts as a catalyst in the reaction process. The electronic properties of the substituents on the compounds influenced the reaction yield. Phenol with the –OMe group produced a

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

• conditions were optimized for the effective formation of tetrahydroquinoline derivatives with varying substituents, showing high yields under mild conditions. Mechanistic studies suggest a catalytic cycle involving nucleophilic attack by the aniline on the cyclobutanone oxime, followed by cyclization to form

• conditions, we proceeded to investigate the generality of this Cu-catalyzed system. Initially, a series of anilines bearing diverse substituents was examined, and the results are summarized in Scheme 2. When copper(II) trifluoroacetate was employed as the catalyst, para-halogen-substituted anilines 1b–e

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• azobenzene derivative 9 [34] to furnish 10. This reaction had to be carried out at −78 °C in order to suppress nucleophilic substitution of the ortho-fluorine substituents in 9 by the thiol 8, a reaction that competes with the desired cross-coupling. For the second Buchwald–Hartwig–Migita cross-coupling, the

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• distance < 5.5 Å is observed. Given the anionic nature of the sulfate substituents, one might expect to observe Me3N+···−O3SO interactions in the crystal. Somewhat surprisingly, only a single short Me3N+···−O3SO contact (4.352 Å) is observed with distance < 4.4 Å. There are, however, numerous longer Me3N

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• is rigidified in a predictable and desired way, by decorating it with an appropriate pattern of fluorine substituents. The purpose of this review is to examine cases where this idea has been put into practice. This topic has previously been reviewed [8], but in the time that has elapsed since that

• dictated by the maximisation of σC–H → σ*C–F hyperconjugative interactions, and this affords different puckers depending on the fluorine stereochemistry [133]. In this sense, the fluorine substituents are performing a similar role to a hydroxy group, so this is a “conformationally conservative” situation

• natural rotameric profile can be restored by replacing the –CH2– moiety of the carbasugar with a –CF2– moiety (e.g., 76, Figure 10), because the electron-withdrawing character of the fluorine substituents enables reasonably effective nO → σ*C1–C(F) hyperconjugation to occur [141]. Another way to influence

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• [48][49]. Thus, in the solution phase, the introduction of fluorine substituents provided seemingly minimal effects on the electronic spectral features of phenacenes. It has been demonstrated that parent phenacenes phosphoresce in a 500–620 nm wavelength region at 77 K showing the clear vibrational

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

• to the parent allyl group, a variety of 2-substituted electrophiles 31 could be applied. These included those bearing alkyl groups of varying steric demand, halides, and both electron-rich and electron-poor aryl substituents. The olefin coupling partner scope was equally impressive, tolerating

• desired products with up to 99% ee. This methodology worked effectively with both pinacol boronic esters (Bpin) and 1,8-diaminonaphthalene boramides (Bdan), showing broad vinylboron substrate scope across alkyl, aryl, and heteroaryl substituents. The practical utility of the enantioenriched alkylboronic

• showed a broad scope, tolerating both 1,1-diborylalkanes with N-tosyl-protected amines and TBS-protected alcohols, as well as substrates containing alkenes and alkynes. Various allylic bromides 46 with electron-rich and electron-deficient aryl substituents worked well, giving homoallylic boronic esters

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• groups, including an additional substitution on C-7, showed potent activity against nematodes. These acyl substituents, particularly the third cinnamoyl group on C-7, may significantly enhance the biological activity. This modification likely represents a key structural feature influencing its activity

• preserved, with chemical modifications focusing on massarilactone H rather than massarilactone D. These modifications should target other regions of the molecule, such as the number and position of acyl substituents. Future research should investigate the stability and selectivity of these compounds, as