3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• adapt a gauche-conformation (∠O3–C21–C22–O4 = 66.9(3)°, ∠O4–C23–C24–O5 = −77.3(2)°), and only the central ethylene glycol can be found in a trans-conformation (∠O5–C25–C26–O6 = −173.0(5)°). Probably induced by the linker, the commonly preferred perpendicular orientation of the naphthyl-units in the

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• /β = 8:1 and 7:1, respectively), the β,β-configured by-products were also formed, which was attributed to rapid anomerization of the lactol acceptor to the more reactive β-anomer during glycosylation. To minimize anomerization, the lactol acceptor was locked in a 4C1 conformation using a 4,6-O

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

• defined by the two aromatic components of the sensor result in an essentially planar conformation at the free state, whereas binding to a naked barium cation results in a perpendicular arrangement between the benzo[a]imidazo[5,1,2-cd]indolizine and the 1,4-phenylene components, thus promoting a blue shift

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

• the donor property but also to lower the energy of the LE state of the PTZ moiety. Notably, while PTZ adopts a non-planar conformation in the ground state, it undergoes planarization in the excited state [16][17]. This conformational change is expected to further enhance the stabilization effect

• . Although the PTZ unit adopts a bent structure in the ground state, it is known to undergo a structural transformation to a planar conformation upon excitation, as the planar geometry becomes more stable in the excited state. For instance, the planarization time constant of a phenyl-substituted

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

• benzamidine derivatives as a novel pH-responsive molecular switch. Keywords: atropisomer; conformation; isomerization; molecular switch; organobase; Introduction pH-Responsive molecular motors and switches are a class of functional organic molecules capable of reversible structural and electronic changes

• behavior, allowing for both tunability and predictability. Among the various types of pH-sensitive molecular switches, those that rely on isomerism caused by the rotation of molecular bonds are attracting attention because they can apply the most basic property of molecular conformation to molecular

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

• stable figure-eight conformation A to a metastable bathtub conformation B with a small energy difference of approximately 2 kcal mol–1 [21]. In this paper, we discuss the effect of the transformation of the carbonyl groups on the conformational change of the figure-eight structure. We thus intentionally

• ruled out. The structures of compounds 3, 4, and 5 were determined by X-ray diffraction analysis (Figure 2). Mono-olefin 3 and bis-olefin 5 adopt a bathtub-like chiral macrocyclic structure rather than figure-eight conformation. Both compounds crystallize as a racemic pair of enantiomers with P21/c and

• temperature. These are attributable to the mixture of conformers with the figure-eight conformation as minor and the bathtub conformation as major conformer with a ratio of ca. 1:7. The obtained temperature-dependent 1H NMR data were subjected to the van't Hoff plot, affording an enthalpy ΔH and an entropy ΔS

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• data, compound 3aa crystallizes in the centrosymmetric spatial group of the monoclinic system. The molecule has a tweezer-like conformation due to π–π interactions between the electron-donating tolyl and the electron-acceptor fragment NC‒C=C‒S. The heterocyclic fragment in the molecule is non-planar

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

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

• accordance with coupling constants and resulting dihedral angles. Keywords: conformational restraints; dihedral angle NMR; half-chair conformation; modified amino acids; pipecolic acid; stereoselective hydrogenation; Suzuki–Miyaura cross-coupling; Introduction Non-proteinogenic amino acids play an

• important role as building blocks for peptide synthesis [1][2][3][4][5], as organocatalysts [6][7][8][9][10] and as enzyme inhibitors [4][11][12][13]. The incorporation of such amino acids into peptides can, for example, influence peptide conformation, the binding affinity to receptors [14], as well as

• broad doublets instead of double-doublets (Figure 2a,b). The lack of a second coupling constant indicates a conformation in between a chair and a boat with a dihedral angle ϕ near 90°, which is necessary for a coupling constant to be around 0 Hz. Half-chair or twist-boat conformations are well known for

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

• projected benzyl groups. For the 1/NaBArF24 complex, the repeating unit shows that both phenylalanine HIMs exhibit the same conformation (e.g., I) where all three benzyl groups are oriented toward the interior of the macrocycle (Supporting Information File 1, Figure S9). From the single crystal data set, we

• -crystal. Li+ complex 2 (Figure 8) represents the complex consisting of HIM in two different molecular conformations I and II, whereas Li+ complex 3 (Figure S19 in Supporting Information File 1) represents a complex consisting of both macrocycles in the same molecular conformation (e.g., I and I

• ). Similarly, Na+ complex 4 (Figure S20, Supporting Information File 1) represents the complex consisting of HIM in two different molecular conformations I and II, whereas the Na+ complex 5 (Figure S21, Supporting Information File 1) represents a complex consisting of both HIM in same molecular conformation, I

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

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

• excited state. This results in a consistently planar conformation for donor b, while donor a can exhibit either a planar or bent conformation, depending on the nature of the substituent, as previously mentioned. This duality between planar and bent shapes is significant, as it contributes to the aromatic

• CT stabilization of the first excited state of the molecule [34]. This observation is further supported by the orthogonal D–A conformation calculated using DFT, which indicates a decoupled interaction between the HOMO and the LUMO (Figure 2). Moreover, compound 5e is the only member of the family in

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

• ) 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

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

• step will occur only from a conformation in which the ethyl group at the former imine carbon stands opposite to the TMS moiety. While the CN double bond of imine 1 became a single bond in complexes 10 and 11 through the hydrocyanation step, internal rotation around this bond is still massively hindered

• that might similarly occur also in related addition reactions of alkenes, for example. After 11E had reacted with TMSCN, adduct 13 forms, 3.8 kcal·mol−1 more stable than the competing unreactive adduct obtained from "Z" conformation. Outside from the catalytic cycle, 12 could be further hydrolyzed in a

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

• . Supporting Information File 1). The calculations were performed with two conformers of FimH, the open and the closed gate conformation, PDB 1KLF [45] and PDB 1UWF [46], respectively. These protein structures differ in the relative orientation of the so-called tyrosine gate, which is formed by Tyr48 and

• binding energies for 6αMan 4 and 3αMan 5 in complex with the closed gate conformation of FimH reflect the experimental data much better than the binding energies calculated for the open gate conformation (where very similar values were obtained for the E and the Z isomers of both compounds). Modeling with

• the closed gate conformation of FimH led to binding energies of −70.01 kcal mol−1 for E-4 and −71.08 kcal mol−1 for E-5 versus −60.96 kcal mol−1 for Z-4 and −59.43 kcal mol−1 for Z-5. These calculation results correspond to the experimentally determined inhibitory potencies which are significantly

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

• composition such that the new molecule has a better-defined three-dimensional shape. Such “small molecule origami” can offer practical benefits. For example, if a drug molecule is pre-organised into the target-binding conformation, it should exhibit the desirable twin characteristics of high potency (since

• compact size of the fluorine atom itself, means that fluorine can be incorporated into an organic molecule as a replacement for hydrogen without drastically altering the molecular volume. Second, the C–F bond is highly polarised. This means that any molecular conformation in which the C–F dipole is

• available to mix with any nearby filled orbital in a process known as hyperconjugation, and any molecular conformation in which such mixing can occur, will be stabilised [5][6][7]. Putting all these concepts together, it is possible to conceive of a process whereby a conformationally flexible lead compound

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• spectra [1]. Moreover, the ethylene bridge creates a cyclic 8-membered core, inverting the thermodynamically stability in favor of the Z boat conformation compared to parent azobenzene, which has a stable E configuration [1][2][3][4]. Preceding studies including azobenzene-based photopharmacophores showed

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

• (CS) conformation consistent with C5 (Figure 8A) [39]. This low-symmetry cage 3e was designed by taking advantage of the geometric rules discovered studying cage 1. We have introduced the term conformational autodesymmetrization to describe this rational approach to accessing low-symmetry cavities [39

• low-symmetry conformation of cage 3 in solution [39]. Due to their stability, we can typically reclaim our cages up to quantitatively after binding or catalysis experiments, often just via a work-up and precipitation. This breadth of available data opens considerable opportunities in computational and

• (increased flexibility) (Figure 9B) [41]. The ability to tune catalytic activity by tuning the cage rigidity, conformation, or dynamics is certainly an advantage rather than a liability [395][398][399][400][401][402]. It is perhaps unsurprising that the balance of rigidity and flexibility [403][404

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

• in the subsequent nucleophilic attack by the acceptor [137]. This α-glycosyl triflate was readily converted to its skew-boat conformation 62 which led to the attack of the glycosyl acceptor 64 from the β-face of the sugar pyranoside ring exclusively to form the 1,2-trans glycoside 65. Thus, the N

Synthesis of new condensed naphthoquinone, pyran and pyrimidine furancarboxylates

• Kirill A. Gomonov,
• Vasilii V. Pelipko,
• Igor A. Litvinov,
• Ilya A. Pilipenko,
• Anna M. Stepanova,
• Nikolai A. Lapatin,
• Ruslan I. Baichurin and
• Sergei V. Makarenko

Beilstein J. Org. Chem. 2025, 21, 340–347, doi:10.3762/bjoc.21.24

• crystal of 5b (Z’ = 3), contains 3 independent molecules, the crystals of 6c and 7a (Z’ = 2) contain 2 independent molecules, with all independent molecules having similar conformation and equivalent geometric parameters within the experimental error limits. The crystallographic data of the structure are

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• analysis oversimplified the system by neglecting to account for potential contributions from different conformers possibly involved in HB interactions. To rectify this problem, we searched for two possible structures for each Me3PO–HB donor pair, where the HB donor adopts a different conformation in each

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• adopted a nonplanar conformation, with one aromatic residue protruding out of the macrocyclic skeleton plane. Adopting such a conformation rendered it possible for the π-electron-rich phenyl ring to interact strongly with π-electron-deficient guest molecules G1 by means of charge–transfer interactions and

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• yellow crystals from the same solution. X-ray crystallography reveals that in the colorless crystal [27], compound 1 adopts a conformation with approximate Cs symmetry, with the plane of symmetry (σ) shown in the top view in Figure 2a. The structure of Cs-1 in this crystal is essentially the same as that

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

• analysis. The geometries of starting materials 1a and 2a’ were pre-optimized in the solvated phase using Gaussian 16 at the PBE0/def2-TZVP/def2-TZVPD level of theory, after a conformation search using Crest [43][44][45][46][47][48][49]. Next, the electrostatic potential map of the iodonium ion 2a’ was

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• intramolecular Michael addition. Preliminary conformational studies on tripeptides including this scaffold in the central position show an extended conformation in solution (NMR) and in the solid state (X-ray). Keywords: fluoroalkyl groups; heterocycles; hydrazino acids; peptides; tetrahydropyridazines

• strategy, the control of the stereoselectivity of the intramolecular aza-Michael addition could be envisaged with various chiral catalysts in further studies. These heterocyclic hydrazino acids, when incorporated into the peptidic structure, appear to confer an extended conformation. These interesting