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

• profound influence through multifaceted solute–solvent interactions [5]. Solvent polarity, hydrogen-bonding propensity, and dielectric characteristics collectively orchestrate stereodivergent pathways through dynamic coordination effects and differential stabilization of transition states. Notably, these

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

• dependency on the nature of the substituent. The observed trend behavior indicates an apparent change of mechanism for thermal relaxation to the E isomer. This was previously observed for NH-PAPs [32] N-PEG-PAPs [20], and for azopyrazolium salts [33]. To obtain a deeper understanding of the transition states

• in toluene to access higher temperatures (Table 6 and Supporting Information File 1, section 3.7). The Eyring plot for NAc-PAP-CN and NAc-PAP-OMe are depicted in Figure 4. Counterintuitively, the calculated thermodynamic data of the transition states show, within the error margin, similar values of

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

• involving adamantyl transfer and TS2 involving tert-butyl transfer (Scheme 9). Analysis of these transition states revealed that both require significant pyramidalization of the transferring carbon center, with the barrier for adamantyl transfer (TS1) being 2.3 kcal/mol higher than that for tert-butyl

• the competing transition states showed that the chiral α-borylalkylcopper species 37 could approach the olefinic moiety of allylic electrophile 35 from either the re- or si-face. The re-face approach is energetically favored, minimizing steric interactions between the bulky aryl substituent of NHC

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

• catalysis has fared best using approaches such as destabilizing ground states by constrictive binding, guiding molecular collisions to reduce large entropic costs (e.g., pericyclic reactions), and broad, undirected coulombic stabilization of charged transition states [36], for example of cations by

• electrophile [175]. In terms of polarization, since cages are invariably charged [36], a few MOCs have demonstrated charge stabilization of transition states (Figure 5B). A key example uses the highly successful Raymond gallium-based cages, exploited by Raymond, Bergman and Toste [21][37][107][155][165][168

• preorganization to catalyze new reactions, better stabilize transition states, or provide new selectivities. The study of discrete, soluble cavities in solution before translation to lattice analogues might prove a fruitful avenue. Covalent organic cages Covalent organic cages [235] are any discrete assembly, at

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• and frequency calculations of closed-ring isomers (closed) and transition states (TS) were carried out using Gaussian 16 Rev. C.01 program package. The TS structure was optimized using Opt = TS keyword with Berny algorithm. To obey unrestricted Kohn–Sham solution, the broken-symmetry guess was

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

• enantio-determining transition states. Based on the mechanistic studies, a reaction mechanism is proposed in Figure 14. First, the in situ-generated Cu(I)–CN complex 83 is oxidized at the anode to form a Cu(II)–CN complex 84, which reacts with diarylphosphine oxide 80 to generate a transient P-centered

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• met convergence criteria. Consistent with the PES scan outcome, the NEB-CI approach also indicated that the SN2 mechanistic proposal (Figure 2, path 2) dominates. Finally, for both mechanistic pathways, all intermediates and transition states were subjected to optimization and frequency calculations

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• exergonic from Rprop. These results show that the presence of N,N-diisopropylethylamine as base makes this process more energetically feasible by substantially stabilizing the transition states and intermediates in the pathway. These results are strongly supported by the experimental data. In a previous

The charge transport properties of dicyanomethylene-functionalised violanthrone derivatives

• Sondos A. J. Almahmoud,
• Joseph Cameron,
• Dylan Wilkinson,
• Michele Cariello,
• Claire Wilson,
• Alan A. Wiles,
• Peter J. Skabara and
• Graeme Cooke

Beilstein J. Org. Chem. 2024, 20, 2921–2930, doi:10.3762/bjoc.20.244

• otherwise. The absence of transition states was confirmed by the absence of imaginary frequencies in vibrational frequency calculations. The long side chains were replaced by methyl units to aid the convergence of the geometry optimisations. Crystallography Single crystal X-ray diffraction data for 3b were

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• which is being abstracted simultaneously interacts with the carbon possessing the tetrafluoroethylene fragment. At this time, transition states TS1 or TS2 are possible, but the reaction proceeds exclusively through the transition state TS1 to avoid significant steric repulsion between the substituent R

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• confirm that the relaxed structures correspond to local minima (no imaginary frequencies) or transition states (one imaginary frequency). The reaction simulations were run in chloroform using the “Solvation Model based on Density” (SMD) [36] at 273.0 K to reproduce the most commonly used experimental

• favourable process. During the study, it will be observed that several transition states (TSs) can lead to the same product. As there is no possible interconversion between the reactant states, the different reactions will be considered independent, and it will be necessary to use an effective rate constant

• activated CO2 was found to proceed through two transition states. The calculations showed that the breaking of the O–CH(CH3) bond was more kinetically favourable, with a TS 7.6 kcal·mol−1 lower in free energy than the corresponding TS for breaking the O–CH2 bond. The electron-donating nature of the methyl

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• . Optimized structures are shown for the cyclization transition states (hydrogen atoms are omitted for clarity and bond lengths are given in Å). Scope of cyclization reaction. Reactions of di- and trisubstituted alkene substrates. Optimization of cyclization reaction. Supporting Information Supporting

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• reversible coordination of BINOLs 13 or 21 to the prenyl- or geranylboronic acids 14, favouring one of the four possible chair-like transition states. The reaction scope for indoles 15 was demonstrated on a limited set of 5-methoxyindole, 5-bromoindole, and 4-indolyl-pinacol boronates reacting with E- and Z

• 24, which supported the hypotheses regarding the selectivity-determining transition states arrangement. It is important to note, that boronic acids 14 are highly sensitive to oxidation by air and could only be purified in air-free conditions and stored in airtight containers. Additionally

• –Sakurai reaction of allyltrimethylsilane with N-Fmoc aldimines. The pyrrolidine unit gem-methyl group conformational control in the squaramide-based catalyst [34]. The energetic difference between the transition states of the two proposed modes of the reaction (SN1 and SN2 mechanisms). The concerted SN2

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• of interest is the selectivity (either enantio- or diastereoselectivity), which is predicted as the difference in energies between the selectivity-governing transition states ∆∆G‡ (Figure 3). Whereas the application of the above described representations and models to such problems is rather modern

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• curcumins 1 with arylidenemalonate 2 can be explained in terms of the relative stereochemistry of the substituents in the enolate arising from the first Michael addition (Figure 3). Comparison of the two possible transition states TSI and TSII for second Michael addition suggests that a severe 1,3-allylic

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• to be driven by stabilizing non-covalent interactions. Specifically, the carbonyl O in N2-s-cis shows NCIs with one of the benzene rings of PPh3 as well as a hydrogen bond-like NCI with a H-atom of the electrophilic methyl. Thus, the partitioning between transition states favor the N2-pathway over

• system (Figure 10). Under conditions A, deprotonation and cesium coordination were heavily favored by 11.1 kcal/mol (18(N-H)). Transition states 18-N2-Cs and 18-N1-Cs were found leading to N1- and N2-products, respectively. NCIs between the cesium cation with the ester and sulfonate oxygens, and

• heavily favored in complex with Cs+ by 20.6 kcal/mol under conditions A, and 13.6 kcal/mol under conditions B. Transition states were found for the reaction of 21 under both conditions (see Supporting Information File 1). However, in this case, neither chelation nor other NCIs resulted in an energy

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• PIDA/AlCl3, 1:2). Overall, we characterized four transition states along the reaction coordinates for both pathways. Although the PIFA-assisted mechanism follows a similar route to that described in Figure 1 until the formation of the active chlorinating species, in this case, the formation of TS2

• AlBr3 (Figures S5 and S6, Supporting Information File 1). Calculations indicated that each of these pathways proceeds along four transition states. Moreover, we found that the coordination of AlBr3 to I-2 to form TS2 has the highest energy barrier (determining step, ΔG‡ for TS2 53.3 kcal/mol) in the

• presence of PIDA. Meanwhile, formation of TS3 (ΔG‡ = 21.3 kcal/mol) is the limiting step of the mechanism in the presence of PIFA. Then, in the presence of the PIFA/AlBr3 system, bromination of 2-naphthol is the energetically most favored pathway. Although all these reactions occur through four transition

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• chemically-induced cationic cyclization mechanisms, we performed quantum chemical calculations [mPW1PW91/6–31+G(d/p)/SMD(chloroform)] [13][14][15][16][17][18][19][20] to obtain the relative free energies of the cationic intermediates and transition states that interconvert them, as well as the relative free

• higher free energy barriers of 38.0 and 38.8 kcal mol−1, respectively, to react through their associated chair–boat Cope transition states (Figure S11, Supporting Information File 1). In addition, the resulting products were predicted to be approximately 10 kcal mol−1 higher in free energies than the

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• the minimum geometries are reported, as no transition states were obtained because the carbocation ring formation is a spontaneous process. Moreover, it is noteworthy that for each cation optimized, we examined several other conformers (specifically rotamers), but these were of higher energy than the

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• vicinal proton. These results suggested that the formation of the allylic cation occurred readily from alcohols 15 and 18; however, the transition states leading to the rearrangement products were inaccessible and so only chloride addition occurred. The generation of the rearrangement products from the

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• linear or nearly linear transition states [76]. Isotope effects can also be maximized when the acid strength is the same on both sides of the reaction [77]. On the one hand, small variations observed here with different substrates and ligands could reflect the modulation of acidity from the presence of

Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• cubic box of 30 Å side. The k-point sampling was performed through the Gamma–Pack scheme with one point. Transition states were obtained through the climbing image version of the nudged elastic band algorithm [32] and dimer method [33]. These structures showed a single imaginary frequency or with some

• -TEM images and movies will provide us a deeper understanding of fullerene coalescence processes in peapods. Computational Methods The Amsterdam Density Functional (ADF) code [21][22] was used for the electronic structure calculations and to optimize reactants, products, intermediates and transition

• states. The Perdew, Burke and Ernzerhoff (PBE) functional provided the electronic density [23]. Electrons were described with Slater-type basis functions of triple-ζ + polarization quality. We have included scalar relativistic corrections using the zeroth-order regular approximation (ZORA) formalism

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• , stands for the stabilization of anionic transition states on π-acidic aromatic surfaces. Anion–π catalysis on carbon allotropes is particularly attractive because high polarizability promises access to really strong anion–π interactions. With these expectations, anion–π catalysis on fullerenes has been

• catalysis; electromicrofluidics; enolate addition; ether cyclizations; fullerenes; Introduction Anion–π catalysis was introduced ten years ago [1]. The idea is to stabilize anionic transition states on electron-deficient, π-acidic aromatic surfaces (Figure 1A). The true beginning is arguably in 2015

• polarizability [9][10][11], the dream scaffolds for induced anion–π interactions are carbon allotropes. Anionic transition states placed on C60 fullerenes 1 will drive the 60 π electrons toward the other side, thus inducing a transient macrodipole that will stabilize the same transition state that induced its

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• investigated the biosynthetic pathways using DFT calculations to validate the above-mentioned aspects. Results and Discussion The detailed structures of the intermediates and transition states were elucidated by computational analysis. Interestingly, we have found an interaction between the secondary