Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• excellent conversion rates (up to 95% yield) and high enantioselectivity (up to 96% ee). Notably, isoquinoline derivatives containing polycyclic naphthalene moieties or ortho-substituted phenyl groups also demonstrated good reactivity and compatibility. DFT calculations indicated that the C–Se bond

• products demonstrated complete E-stereoselectivity (E/Z ratio >20:1). Notably, under the same reaction conditions, aliphatic selenols remained unreactive. Density functional theory (DFT) calculations revealed that the rate-determining step involves the nucleophilic attack of the selenium anion in

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• given in Supporting Information File 1, Figure S1). In addition to the calculations already outlined, a series of toxicity properties of methyl laurate were calculated using ADMETLab 3.0 in comparison with common organic solvents and some green solvents. The obtained results were visualized with a

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• . This further corroborates the decisive role of the macrocyclic architecture in the anion recognition process. Quantum chemical calculations were performed with the ORCA 5.0.3 software [29]. The geometry optimization was performed by using B3LYP with the def2-SVP basis set. As illustrated in the

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• conformation of the substrates, thereby modulating their reactivities. Density functional theory calculations show that 22 prefers to proceed its annulation through TS22b (ΔΔG‡ = 0) to afford 23 rather than that via TS22a (ΔΔG‡ = 1.5 kcal/mol). In contrast, annulation of 30 undergoes through the low barrier

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• product 49 (Scheme 11, path a). When aryl or alkyl substituents were introduced on the alkyne moiety, a more stable vinylidene intermediate 50 was formed via a 6-endo-dig cyclization, ultimately leading to the generation of the bicyclo[3.3.1]nonadiene product 51 (Scheme 11, path b). DFT calculations

• cleavage to form the boronated phenanthrene framework 170. It is worth mentioning that a unique skeleton rearrangement, supported by DFT calculations, was proposed in this work, which was unprecedented in BiCl3-promoted cyclization. Conclusion This comprehensive review has systematically delineated the

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• % reference for clearance calculations. HPLC–MS analysis. The semi-quantitative determination of test compounds was carried out using a Waters Xevo G2-XS QToF mass spectrometer equipped with an electrospray ionization (ESI) source operating in positive ion mode. Chromatographic separation was performed on a

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• secondary amines through the combined use of a m-quaterphenyl probe 1 and theoretical calculations. The probe 1 is covalently attached to chiral amines to form conjugates that exhibit exciton-coupled circular dichroism (ECCD) in the m-quaterphenyl chromophores. The calculated ratios of the P and M

• conformers, obtained via DFT calculations, show a correlation with both the sign and intensity of the experimentally observed CD spectra. Keywords: absolute configuration; chiral amine; chiral quaternary ammonium salt; circular dichroism; DFT calculation; Introduction Determining the absolute

• effect in CD, the direction of twist can be estimated. The absolute configuration of amines can be determined by comparing the direction of the twist determined by CD with that obtained by conformational analysis using theoretical calculations. However, this method has only been applied to simple primary

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• mixture of propargyl alcohol 50 (0.7 mmol), NaN3 (2.8 mmol), n-Bu4NI (0.5 mmol) and MeCN (10 mL) under electrolysis (graphite rod as anode, stainless-steel plate as cathode, 11 mA) at rt for 10 h. According to the experimental results and density functional theory (DFT) calculations, a plausible mechanism

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• calculations, and chemical transformations. Biologically, these molecules exhibit antineuroinflammatory activity against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells. Structurally, these molecules generally have a tetracyclic backbone (A–D rings), among which AB rings form a bridged

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• combined with state-of-the-art multireference quantum mechanical calculations to understand the photophysical properties and mechanisms of these diazabicyclo[2.2.1]heptenes. The energetically accessible lowest excitations are nNN(σCN) → π* and range from 3.94–3.97 eV. From the >292 trajectories, the

• , thereby explaining the observed selectivities. A minority of trajectories undergo thermal conversion in the ground state, producing the minor retained housane product from inverted housane/diradical. Keywords: non-adiabatic molecular dynamics; photochemistry; quantum mechanical calculations

• calculations have provided valuable insights into the photochemical stereoselectivities of cyclic azoalkenes. In 1998, Yamamoto and co-workers investigated the reaction paths for α-C–N and β-C–C bond cleavage during the direct and sensitized photolysis of DBH [81]. The minimum energy geometries in S0, S1, T1

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• density functional theory (DFT) calculations were obtained. Results and Discussion Photoreduction of 2-benzoylimidazolium triflate with diisopropylethylamine Initial investigations To investigate the potential for the light-mediated reduction of acylazolium salts, compound 1 was prepared as a

• , however, did not reveal any significant change in the absorption profile. To gain further insight, time-dependent density functional theory (TD-DFT) calculations were carried out (for details of the computational studies, see Supporting Information File 1). In line with the UV–vis studies, comparison of

• ][26][27][28][29][30]. The TD-DFT calculations also provided insight into the nature of the subsequent mechanistic steps where the excited benzoylimidazolium 1* is converted to the reduced zwitterionic alkoxide species E in the presence of DIPEA (Scheme 2). This requires the transfer of both an

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• , theoretical calculations were performed to evaluate the energy barriers of isomerization. As shown in Figure S3 (Supporting Information File 1), the configuration observed in the crystal structure has the lower energy by 24.0 kcal mol−1 than that of the isomeric structure with two pyrene units at the same

• macrocycles, theoretical calculations on the frontier molecular orbitals were carried out based on the optimized structures. As shown in Figure 4, the distributions of the highest occupied molecular orbitals (HOMOs) are disjointed from that of the lowest unoccupied molecular orbitals (LUMOs). Specifically

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• concentration of the photoswitch in solution: when MeOH or water are present, the lifetimes drop significantly, and particularly at pH 4, as consequence of more favourable intermolecular proton transfer. Calculations show that water molecules bridging between two Z-isomers favour the formation of hydrazone and

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• advanced materials, particularly those whose properties rely on the polarity and spatial arrangement of C–F bonds within a cyclopropane framework. Keywords: cyclopropane; fluorination; polarity; theoretical calculations; Introduction Cyclopropane, the smallest cycloalkane, has a rigid structure that

• substitution is endothermic and, therefore, destabilizing [8]. This destabilization was attributed to the greater s-character of the orbital involved in bonding to the substituent. In contrast, our calculations at the B3LYP-GD3BJ/6-311++G(d,p) level revealed that the reactions leading to the fluorinated

• of organofluorine compounds [24]. Frequency calculations confirmed the absence of imaginary frequencies, ensuring the structures correspond to true minima, and provided standard Gibbs free energies. For the dimer of 1.2.3-c.c. and its complexes with Na+ and Cl−, basis set superposition error was

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• to form oxazolo[3,2-c]pyrimidine derivative 7 (Scheme 7). The highly diastereoselective formation of product 7 can be explained based on the theoretical calculations by Elliott et al. of aza-Diels–Alder reaction of vinyloxazoline with TsNCO [19]. According to their investigations, the aza-nucleophile

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• process hazards through the evaluation of thermal safety parameters and DFT calculations revealed catalytic and solvent effects of ionic liquids in nitration [9]. In addition, researchers have focused on improving nitration processes through process intensification strategies by integrating advanced

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• . The remedy for Parkinson’s disease, piribedil, was obtained in high yield. The plausible mechanism of the elaborated process was proposed and supported by DFT calculations. Keywords: amines; DFT; hypophosphites; reductive amination; role of cations; Introduction Sodium hypophosphite, NaH2PO2, is one

• the DFT calculations (Scheme 5, Figure 2). Firstly, reductive amination of an aldehyde started from a nucleophilic addition of the amine to the carbonyl group of the aldehyde. In the presence of acid, this step could occur via acidic catalysis involving a protonation step of an amine (Step_2) or

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• cyclization of functionalized phenyl isocyanides, guided by DFT calculations (Scheme 2b) [29]. Three types of isocyanides (10–12) were evaluated in reactions with aryl iodides, affording indole-fused N-heteroaryl scaffolds 13–15, featuring either a C–C or C–N stereogenic axis, in moderate-to-high yields with

• identified. While the employment of L9 afforded endo-selective [3 + 2] cycloadducts 60, using Trost ligand L10 resulted in a complete reversal to the exo-cycloadducts 61. DFT calculations were performed and indicated that these two ligands act in different ways in the cyclization process, providing

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• decoupling between the para-phenylene and benzo[a]imidazo[5,1,2-cd]indolizine components that results in a blue shift upon Ba2+ coordination. Keywords: aromaticity; DFT-TDDFT calculations; double-beta decay; fluorescent sensors; polycyclic arenes; Introduction Double beta-decay [1] is a radioactive decay

• values. Our calculations show that, as expected, 12-crown-4 16a and 15-crown-5 16b are too small and consequently the barium cation lies outside the average molecular plane determined by the macrocycle. In the case of 18-crown-6 16c, the cyclic ligand accommodates very well the cation, which is now

• . We chose compound 18 (Figure 5) as a convenient computational model. We calculated the energy profile associated with the rotation between the 1,4-phenylene and benzo[a]imidazo[5,1,2-cd]indolizine 1 components, defined as variation of the ω = a–d–c–d dihedral angle shown in Figure 5. Our calculations

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• an in-plane aromatic transition state, is analogous to the first step of this transformation, known as Hopf cyclization. Indeed, our calculations [85] indicate that the parent Hopf cyclization involving cis-hexa-1,3-diene-5-yne occurs in a concerted manner through a transition state that features in

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• spectra were simulated by time-dependent density functional theory (TD-DFT) calculations (TD-MN15/6-31G(d)//MN15/6-31G(d). The calculated rotatory strengths of (Sp)-6 and (Sp)-7 were plotted with their observed CD spectra in Figure 3A and 3B, respectively, and the calculated CD spectra are shown in

• ). Molecular orbitals of (Sp)-6 and (Sp)-7 in their ground and excited states were calculated using DFT and TD-DFT calculations (Figures S20–S23, Supporting Information File 1). In both molecules, the orbitals were localized to part of the π-conjugation systems rather than the whole system in the ground and

• excited states due to the twisted structures by the π-stacked [2.2]paracyclophane moieties. The CPL behaviors of (Sp)-6 and (Sp)-7 were investigated by TD-DFT calculations; namely, the electric transition dipole moment (μ), magnetic transition dipole moment (m), and the angle (θ) between μ and m in the S1

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• synthesized and characterized (Figure 1). Their photophysical properties were comprehensively examined by steady-state and time-resolved emission and absorption spectroscopy. Furthermore, time-dependent density functional theory (TD-DFT) calculations were performed to support the experimental findings

• shown in Supporting Information File 1. Energy levels and steady-state optical properties Time-dependent density functional theory (TD-DFT) calculations were performed to gain insights into the electronic structures of Pe–PTZ derivatives at B3LYP/6-31+G(d,p) level of theory (Figure 2) [18]. The

• calculations revealed that the highest occupied molecular orbitals (HOMOs) are localized at the PTZ or PTZ–TPA moieties in all compounds. In contrast, the lowest unoccupied molecular orbitals (LUMOs) are localized at the Pe moiety. This spatial separation of frontier orbitals suggests a weak electronic

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• hypothesis that the rotational barrier of the benzamidine changes upon protonation, density functional theory (DFT) calculations were performed for the C–N and C–N/C–C rotations of the molecular form and of the protonated 2-bromo-N,N,6-trimethylbenzimidamide as a model compound (Figure 2). Several transition

• effect of the C–N rotation due to the decrease in pH. As the rotation of the C–N bond of the ortho-disubstituted benzamidine could be controlled by the protonation of the amidine moiety, we then focused on the chiral axis of the ortho-disubstituted benzamidine. Our DFT calculations suggested that the

• . Notably, at pH 9.2, racemization proceeded minimally, even under high temperature conditions. Furthermore, it was confirmed that racemization requires a higher pH where a higher proportion of the amidine exists in its molecular form. This result was consistent with our DFT calculations, which showed that

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• -dichloroethane and highlight its potential for temperature sensing applications. Density functional theory calculations were performed to support our findings and to investigate the mechanisms of azobenzene–acid interactions, aiming to guide the design of azobenzene-based temperature sensors in future research

• = 98–144 nm) between compounds 1–3 and their protonated counterparts (1H+–3H+; Figures S16–S18 in Supporting Information File 1). The experimental results are enticing from the applications point of view but offer little insight into details of the azobenzene–acid interactions. DFT calculations were

• calculations revealed that a second acid molecule significantly enhances protonation, prompting further investigation into the reaction stoichiometry. Upon protonation of 3, the n → π* transition disappears and the π → π* transition red-shifts from 358 nm to 502 nm (Figure 1B), resulting in a visible color

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• calculations assume a commensurate hexagonal lattice. The graphite lattice directions are marked by the 3-black arrows. The unit cell parameters of optimized geometry (a = 1.968 nm, b = 1.968 nm and γ = 120°) match well with the experiments. The microscopic arrangement of the molecules is clearly visible. It

• voltage, which is ≈1.1 V. This suggests that while switching, the molecules may not be in their neutral state. Since the graphite–molecule interaction is weak and van der Waals-type, we use the gas-phase calculations and no major change in the electronic structure is expected for molecules upon adsorption

• memory. A pre-optimized two-layer graphite was used from the library data as provided in the Quantumwise DFT package. The lattice parameters for graphite are, a = 2.4612 Å, b = 2.4612 Å, c = 6.709 Å, and α = 60°. Molecular orbitals were obtained from the calculations performed using the Gaussian 03