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

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

• absorption bands derived from the Pe moiety between 390 and 450 nm. A broad absorption feature around 320 nm, whose intensity increased with the number of TPA groups, was also observed. The increase in the absorption with the increase in the number of TPA groups is reproduced by TD-DFT calculations (Figure

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

• = 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

• obtained, irrespective of initial acid concentration (Supporting Information File 1, Table S10). This suggests that upon protonation, 3 forms an ion pair with two MSA molecules (3H+MSA−MSA), as supported also by DFT calculations. Assuming the 1:2 stoichiometry between 3 and MSA, the reaction thermodynamics

• target solvent). Samples of desired azobenzene concentration were then prepared by dilution from stock solutions into the desired acid–solvent mixture. DFT calculations were performed with ORCA 6.0.1 [33] using the ωB97X-D4/def2-SVPD method. The conductor-like polarizable continuum model (CPCM) was used

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• nucleophilic substitution of the thus generated alkoxide to form an oxygen-containing five-membered ring. At least, density functional theory (DFT) calculations support that the nucleophilic attack of methylenetriphenylphosphorane to the exo-methylene unit is slightly favorable over reaction with the carbonyl

• signals due to the exo-methylene groups overlapped with the solvent signal in CD2Cl2. The thus obtained activation barriers of 3 and 5 were 11 and 12 kcal mol–1 at 263 and 253 K, respectively (Figure S27 in Supporting Information File 1). Previous DFT calculations at the B3LYP/6-31G(d) level of theory

• suggested that the bathtub conformation of CBBC 1 is slightly unfavorable than the figure-eight conformation by 2.4 kcal mol−1 [21]. On the other hand, the current DFT calculations suggest that the bathtub conformation of bis-olefin 5 is rather favorable by 0.3 kcal mol−1, which is in accordance with the

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• loadings were necessary for ortho-substituted phenyls. Control experiments and DFT calculations revealed that the oxetane ring is formed before the tetrahydrofuran in the domino process. In 2023, Shigehisa and co-workers published a new cycloisomerisation strategy for the construction of oxetane rings from

• halogens, nitriles, alkenes and heteroaryls. On the other hand, this methodology suffers from relatively low diastereoselectivity as the dr lies between 1:1 and 2:1. DFT calculations suggested the reaction proceeds through nitrogen elimination, oxonium ylide 119 formation, homolytic cleavage and radical

• groups including esters, ketones, sulphones and heteroaryls. The mechanistic proposal, supported by DFT calculations, starts with an oxidative decarboxylation to give an aminooxetanyl radical 157. This species is in turn coupled with the aryl halide by the active Ni(0) catalyst (generated in situ by

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• of the diverse range of azulene-embedded nanographenes discussed in this review presents a significant challenge, as many of the original studies lack comprehensive data. In numerous cases, fluorescence characteristics were not thoroughly examined, and time-dependent density functional theory (TD-DFT

• ) calculations – essential for accurately identifying the S0→S1 electronic transitions – were not reported. Nevertheless, certain general structure–property relationships can still be proposed for these systems. Representative examples of polycyclic aromatic hydrocarbons (PAHs) featured in this review are

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

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

• chemistry’s structural variability. Cao et al. [14] developed an automated workflow that predicts the regioselectivity of C–H activations using extensive DFT calculations on a HPC cluster using up to 600 nodes, each containing 16 Intel Xeon E5-2670 cores. They considered two possible reaction mechanisms, an

• and usability since several DFT calculations need to be run on an HPC cluster in order to make a prediction. In this study, we introduce a quantum mechanics (QM)-based computational workflow specifically developed to predict regioselectivity in C–H functionalization reactions involving directing

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

• chromatography with 30:70 EtOAc/hexanes. Product structures were confirmed by 1H and 13C NMR analysis and X-ray crystal structure analysis of 8a. Density functional theory (DFT) calculations DFT computations were conducted utilizing Gaussian 16W with the B3LYP functional and the 6-31G(d,p) basis set [21][22

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

• difference in binding constants as well as the isolation of two distinct molecular conformations of phenylalanine HIM 1 (Figure 1), DFT calculations were performed. The details of DFT calculations are shown in Table 1. For DFT calculations, we assigned two HIM macrocycles per LiBArF20 as found in the co

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

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

• allylic amination of acetate 12 with isatin (11a).a Supporting Information Data of thermal racemization of 7, DFT calculations for investigating racemization mechanism of 7, general methods and materials, experimental procedures and characterization data, 1H, 13C and 31P NMR spectra for 9 and 10, 1H, 13C

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

• bridge cycle [36][37]. The excellent diastereoselectivity in this radical cyclization was further rationalized by DFT calculations, which suggests an energy discrepancy of the hydrogen atom transfer process from different faces of the resulting α-hydroxyl radical. Final reduction of the ketone and amide

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

• to break the symmetry. Here, the molecule consists of a pentalchloro phenyl and two tribromophenyl units (PCl-TBr2M) [55], or with two p-bromotetrafluorophenyl rings (PCl-TFBr2M) (see Figure 2d–f) [52]. DFT calculations for these mixed per- and trihalophenylmethyl radicals and their orbitals show a

• = 697 nm with 2% (in cyclohexane) [10]. DFT calculations display that the Cz unit acts as an electron-donor moiety, facilitating a CT excited state with a clear C2 symmetry (see Figure 5b). Similarly, a biscarbazolylanthracenylmethyl radical has been reported; however, the ϕ has been too low to be

• (because of spin selection rules forbidding the direct transition from the quartet to the doublet state). While for TTM and PTM substituted with weak donors such energetically low-lying quartet (Q1) states have been observed in TD-DFT calculations [20][62] and EPR spectroscopy [63], there are no such

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

• thiols act as stoichiometric reductants. Mechanistic insights, elucidated through control experiments and DFT calculations, revealed that photoexcitation of diazo imide 41 triggers nitrogen extrusion (ΔG‡ = +10.0 kcal·mol−1), generating the triplet carbene intermediate Int-45. In DCM, this species

• substrates 61. At 10 °C, the catalytic system consisting of NiBr₂(diglyme), oxazoline ligand, (EtO)₃SiH, and K₃PO₄(H₂O) achieved β-selective hydroalkylation. When the temperature was raised to 100 °C, the reaction selectively produced α-branched products. DFT calculations showed that at low temperatures, the

• mechanistic experiments and DFT calculations, the authors proposed a possible mechanism for the reaction: first, DPZ is excited by light to form the excited state DPZ*, which then oxidizes bromide ions through single-electron transfer to generate corresponding radical anions. These radical anions undergo

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• solution into chloroform and controllable release into acidic solution [32]. Very recently, it was found that the receptor L alone can further extract solid Li2SO4 into DMSO solution [33], where sulfate binding is sufficiently strong to drive the solid–liquid extraction. DFT calculations suggest that an

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

• often show higher quantum yields and increased thermal half-life of the metastable state. For the half-life, the choice of the heterocycle is crucial, as revealed through density functional theory (DFT) calculations, which showed that a 5-membered ring promotes the stability of the Z isomer [30]. Within

• predicted using quantum chemistry to describe the Z→E isomerization in azobenzenes, namely: rotation, inversion, inversion-assisted rotation, and concerted inversion depending on the structure of the azobenzene [40][41][42][43][44]. For PAPs, Calbo et al. showed by DFT calculations that the inversion

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

• , while density functional theory (DFT) calculations provided insights into their electronic properties, including reactivity and stability. This comprehensive approach, integrating synthesis, biological evaluation, and computational methods, highlights the potential of 4-(1-methylamino)ethylidene-1,5

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

• hydrocyanation of hydrazones, catalyzed by a calcium–BINOL phosphate complex, has been studied for the first time both experimentally and computationally with DFT methods. A full catalytic cycle for the enantioselective synthesis of α-hydrazinonitriles is proposed based on insights gained from DFT calculations

• –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

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

• traditional crotyl addition to acetaldehyde. This methodology represents the first example of highly enantio- and diastereoselective copper-catalyzed allylic substitution that controls vicinal stereogenic centers. DFT calculations revealed that the high enantioselectivity (98:2 er) originates from a face

• copper complex formation and subsequent selective olefin insertion results in the high levels of enantioselectivity (98:2 er) observed experimentally. DFT calculations further elucidated the origin of the high diastereoselectivity (up to 96:4 dr) in the allylic substitution step (Scheme 13b). Analysis of

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

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

• (Figure 9A) [39][40]. For cage 1, DFT calculations suggests a population consisting of perhaps two major conformers (C5, C9), with 3–4 minor contributors (298 K, THF) [39][40], but we can control the preference of these conformers by introducing functionality which favors particular amide orientations [39

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