Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• 25 with vinyl butanoate and PPL delivered monoester 26 in 92% yield (99% ee). The axial chirality was transferred to the C7’ stereocenter through a Ag(I)-catalyzed cycloisomerization of the allenol, constructing the dihydrofuran ring. Lipase-catalyzed ester hydrolysis provided allylic alcohol 27

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

• ; inherent chirality; N-doped macrocycle; nonplanarity; regioselective cyclization; Introduction Chiral macrocycles have attracted significant research interest owing to their diverse applications in enantioselective recognition [1][2], catalysis [3][4], and circularly polarized luminescence [5][6

• ]. Generally, chirality in macrocycles arises from subunits featuring classical chiral elements [7], such as central, axis, planar and helical configurations. In contrast, inherent chirality represents a non-classical phenomenon where chirality emerges from the rigid and nonplanar architecture of macrocycles

• that inherently lacks symmetry [8][9]. One of the most typical representatives are calix[4]arenes (Figure 1a), first reported by Böhmer in 1994 [10], where asymmetric substitutions on the macrocyclic rim induce inherent chirality. Subsequent advancements have identified other inherent chiral systems

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• .21.145 Abstract Chiral molecules, distinguished by nonsuperimposability with their mirror image, play crucial roles across diverse research fields. Molecular chirality is conventionally categorized into the following types: central chirality, axial chirality, planar chirality and helical chirality, along

• with the more recently introduced inherent chirality. As one of the most prominent chiral organocatalysts, chiral phosphoric acid (CPA) catalysis has proven highly effective in synthesizing centrally and axially chiral molecules. However, its potential in the asymmetric construction of other types of

• molecular chirality has been investigated comparatively less. This Review provides a comprehensive overview of the recent emerging advancements in asymmetric synthesis of planarly chiral, helically chiral and inherently chiral molecules using CPA catalysis, while offering insights into future developments

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

• led to a strong decrease in the thermal half-life, suggesting water is also involved in the Z–E thermal isomerisation process [70]. Bridged indigos have also been reported for which the Z-isomers are unstable. By bridging the two nitrogen atoms, these compounds show planar chirality and can be

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• the single crystals of racemates significantly differs from that of optically pure forms (chirality-dependent halogen bonding, Figure 1) [20][21]. That is, in crystals of racemic mebroqualone rac-I, heterochiral zig-zag polymer chains, in which (P)-I and (M)-I were alternately connected, were formed

• , ought to have different halogen bonding properties, and should be explored as different chemical entities. Meanwhile, there are very few studies on halogen bonding related to molecular chirality such as those shown in Figure 1 [27][28][29][30]. In addition, the studies on the comparison of

• intermolecular interaction (halogen bonding) between chiral compounds possessing an amide group and a thioamide group are quite rare [21]. We were curious as to whether the chirality (racemate/optically pure form)- and the functional group (C=O/C=S)-dependent halogen bonds found in I and II are also observed in

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

• ). Keywords: BINOL; chirality; crown ethers; macrocycles; supramolecular chemistry; Introduction Crown ethers are at the heart of supramolecular chemistry [1]. Ever since their discovery in 1960, a vast number of different crown ethers has been synthesized and their interactions with guest molecules have

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

• Jia-Yu Liao College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China 10.3762/bjoc.21.129 Abstract Beyond the conventional carbon-centered chirality, catalytic asymmetric transformations of isocyanides have recently emerged as a powerful strategy for the efficient synthesis

• of structurally diverse scaffolds featuring axial, planar, helical, and inherent chirality. Herein, we summarize the exciting achievements in this rapidly evolving field. These elegant examples have been organized and presented based on the reaction type as well as the resulting chirality form

• . Additionally, we provide a perspective on the current limitations and future opportunities, aiming to inspire further advances in this area. Keywords: axial chirality; helical chirality; inherent chirality; isocyanide; planar chirality; Introduction Chirality represents a fundamental property of molecules

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

• observed between the dimer and trimer, despite the same absolute configuration of the planar chiral [2.2]paracyclophane units, which was reproduced by theoretical studies. Keywords: circularly polarized luminescence; oligomer; [2.2]paracyclophane; planar chirality; Introduction Cyclophane is a general

• molecular structure with stacked π-electron clouds [1][4][5][6]. The distance between benzene rings in [2.2]paracyclophane is extremely short (2.8–3.1Å), and thus the rotational motion of benzene rings is completely suppressed; therefore, planar chirality without chiral centers [7] appears by introducing

• above, the experimental CD and CPL signs of (Sp)-6 and (Sp)-7 were reproduced by the TD-DFT calculations. Molecular orbitals of (Sp)-6 involved in the CPL are obviously curved and twisted, resulting in the opposite chiroptical signs. Twisted chirality is known to result in CPL of π-conjugated molecules

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

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

• formation between carbonyl and alkene units. Keywords: bathtub; chirality; cyclobisbiphenylenecarbonyl; figure-eight; Wittig reaction; Introduction Figure-eight π-conjugated molecules represent chiral macrocycles with a twisted crossover structure [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15

• (P,P)-1, whose configuration was previously confirmed [17]. The (P,P)-figure-eight conformation of CBBC 1 corresponds to the (Ra,Ra)-bathtub conformation, whose configuration is based on the axial chirality of the biaryl segment. Consequently, the 1st fractions of 3 and 5 were determined to be (Sa,Sa

• circle and red triangle mean selected signals due to figure-eight and bathtub conformations, respectively. Simulated dynamics of bis-olefin 5 at the B3LYP/6-31G(d) level of theory. The description for the configuration of A and B are based on the helical chirality of the 1,1-diphenylethylene units and

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• helical architectures, have attracted considerable attention due to their intrinsic chirality and tunable optoelectronic properties. Among them, nitrogen-doped helicenes (azahelicenes) and their heteroatom-co-doped counterparts – such as B/N-, O/N-, S/N-, and Se/N-doped helicenes – have emerged as highly

• systems – has granted access to increasingly complex helicene frameworks with well-defined chirality. This review systematically summarizes recent advancements in the synthesis, structural engineering, and chiroptical performance of nitrogen-doped helicenes and their heteroatom-doped derivatives

• ; optoelectronic applications; Introduction Helicenes, a class of non-planar polycyclic aromatic hydrocarbons characterized by ortho-fused aromatic rings forming a helical framework, have attracted significant attention due to their inherent chirality, unique optoelectronic properties, and wide-ranging

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

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

• Education, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan Molecular Chirality Research Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan Soft Molecular Activation Research Center, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan Institute for

• the resulting product (S)-13a in the presence of FeCl3 as the catalyst, the corresponding malononitrile derivative (S)-16 was obtained without any loss in optical purity. Keywords: asymmetric allylic amination; axial chirality; isatin; palladium catalysis; P,olefin-type chiral ligand; Introduction

• ligands with axial chirality for Pd-catalyzed asymmetric allylic substitution reactions. For example, the Zhou group reported a P,olefin-type chiral ligand 3 with C–C bond axial chirality for this reaction (Figure 2) [27]. Additionally, we have recently reported chiral ligands with C–N bond axial

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

• the donor molecule might lead to reduced electron–electron repulsion in the extended systems improving the emission characteristics [66]. Circularly polarized photoluminescence The TTM-DNC and TTM-DPC with their helical donors are chiral and can be separated for the axial chirality of the helicene

• donor unit (see Figure 11). Chiral chromatography provides access to all four stereoisomers, as both, the helicene and the TTM unit, are chiral (as discussed above). However, the TTM propellers racemize quickly so that effectively one receives the diastereomers with the respective helicene chirality

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 product with opposite chirality was obtained, in comparison to experiments with the in situ formed Ca complex (Table 2, entries 1–3). It appears that the way in which catalyst 6 is generated (pre-formed or in situ), has a major influence on enantioselectivity, while the addition of t-BuOH has

• complex as computed at B3LYP/6-31G* level of theory. Axial chirality configuration of the BINOL phosphate is as used in experiment (i.e., "R"). Bond lengths and distances are given in pm. For discussion see text. Species numbers represent all respective stereoisomeric forms. Reaction energy profile for

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

• from the equator of C1 resulting in a helical geometry [63][65]. Both senses of helical chirality are present in the crystal; values in parenthesis given below refer to the complex with opposite helical chirality. The guest Me6CHDA possesses a mirror plane and is therefore achiral. In solution, host C1

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

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

• catalysts generally produce straight-chain products lacking chirality when reacting with monosubstituted allylic substrates, whereas iridium catalysts selectively generate branched products with high optical purity and precise control over the reaction site. Furthermore, the development of chiral

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• Yasushi Yoshida Maho Aono Takashi Mino Masami Sakamoto Institute for Advanced Academic Research (IAAR), Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan Molecular Chirality Research Center, Graduate School of Engineering, Chiba University, 1-33, Yayoi-cho, Inage-ku, Chiba-shi

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• Henrich Szabados Radovan Sebesta Department of Organic Chemistry, Faculty of Natural Science, Comenius University Bratislava, Mlynská dolina, Ilkovičova 6, 842 15 Bratislava, Slovakia 10.3762/bjoc.21.6 Abstract Axial chirality is present in a variety of naturally occurring compounds, and is

• acids feature as the most prolific catalytic structure. The last part of the article discusses hydrogen-bond-donating catalysts and other catalyst motifs such as phase-transfer catalysts. Keywords: asymmetric organocatalysis; atropoisomers; atroposelective synthesis; axial chirality; stereogenic axis

• ; Introduction Stereoselective catalytic formation of chiral compounds is one of the critical tasks of modern organic synthesis [1]. The catalytic formation of compounds with a center of chirality has been the focus of countless works and can now be considered a matured area. On the other hand, the generation of

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• . Although meso-tetrakis(4-sulfonatophenyl)porphyrin (TPPS4, 54) is an achiral molecule, the respective J-aggregates reveal supramolecular chirality caused by spontaneous mirror symmetry breaking (SMSB) during the aggregation process in an aqueous acidic solution. Using of these aggregates led to

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• conventional synthesis. A similar [2]rotaxane molecule bearing a Co complex exhibited ICD derived from the chirality of CD on the absorption band of the cobalt complex [37]. Afterward, numerous CD-based rotaxane syntheses were reported; they generally contained noncovalent-bond moieties on the dumbbell

• position of the wheel on the axle component. Meanwhile, the ICD evaluation based on the chirality of CD is a powerful tool for analyzing the inclusion behavior, which is also used for structural analysis. In 2006, Tian and co-workers reported the structural control of the rotaxane framework by subjecting a

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• dopants for liquid-crystal compositions. Keywords: chiral dopant; chirality; cholesteric phase; diols; fluorine; helical twisting power; liquid crystal; Introduction Liquid crystals for use in liquid crystal displays (LCDs) have become one of the most prominent application areas of fluoroorganic

• from neat chiral mesogens, or through the addition of a chiral dopant to an achiral nematic liquid crystal [5][6]. The ability of the dopant to induce chirality in the nematic phase is defined as the helical twisting power [HTP; β = (pc)−1; with p the helical pitch and c the molar concentration]. The

• appears, the more efficient is the induction of chirality in a nematic host. Additionally, the location of the chiral substructure within the dopant molecule seems to play a role. A more ‘central’ location within in the mesogenic core structure corresponds to a higher HTP of the resulting chiral compound

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

• a smooth [1,3]-proton shift reaction with a high chirality transfer, affording the corresponding rearranged products in acceptable yields. Without purification, these products were subjected to acid hydrolysis and the subsequent N-Cbz protection, providing the optically active tetrafluoroethylenated

• amides in moderate three-step yields. Keywords: amine; chirality transfer; [1,3]-proton shift reaction; tetrafluoroethylene fragment; Introduction A fluorine atom has quite peculiar chemical and physical properties compared to others, and hence changes in molecular properties resulting from the

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• , they also achieved the construction of C–N axis chirality through remote substitution/cyclization/1,5-H shift process (Scheme 26). The control experiments confirmed that the reaction requires the joint participation of copper and terminal alkyne, and the radical-capture experiment also ruled out a

• , 50a–l) axial chirality in remarkable enantiopurities. Mechanistic studies and deuterium labeling experiments have revealed that the reaction proceeds in a stepwise manner without involving a 1,5-H migration process. Based on these findings, the authors have proposed a mechanism wherein the

• stereoselective aromatization serves as a pivotal step in the transfer of central chirality to axial chirality (Scheme 52). To harness the full potential of CO2 as a renewable and abundant carbon source, He et al. [82] proposed an innovative strategy that married asymmetric yne-allylic substitution with CO2