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

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• supramolecular helices [45]. SEM was used to investigate the structures resulting from the self-assembly of a bis-bipyridinium-based compound (1·4Br) resulting in helical supramolecular fibres with different chirality induced depending on the enantiomer of tryptophan present. The direct images obtained from SEM

• allowed the chirality of the resulting fibres to be easily observed, indicating that the hydrogel matrix induced by racemic tryptophan was comprised of racemic amounts of left-handed (M) and right-handed (P) helices (Figure 8) [45]. Due to the orientational averaging of scattering techniques, directional

• information is lost. Subsequently, extracting information such as chirality cannot be achieved without additional information such as that obtained from direct imaging [46]. A more comprehensive discussion of the capabilities and limitations of scattering techniques is included later in this review. SEM was

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• been widely investigated in the past decades for application as fluorescent dyes [3][4][5], chirality inducers [6][7][8], acceptors for photoinduced electron transfer (PET) [9][10], and components of supramolecular assemblies [11][12][13][14]. Owing to the stable π-electronic systems showing unique

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• in high to excellent yields without detection of any regio- as well as stereoisomers. The chirality contained in amines did not work efficiently for the stereochemical induction of the products (entries 6 and 7 in Table 2). In the case of secondary amines, the sterically demanding dibenzylamine

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

• cleavage of the methoxyphenyl group in aqueous methanol using excess of ceric ammonium nitrate (CAN) as a soft oxidant (Scheme 14). The sequence afforded the target (S)-homoallylic amine 69 in 64% overall yield with a complete retention of chirality. To gain a mechanistic insight into the formation of the

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• center in proximity to the reactive moiety of the covalent substrate adduct to the catalyst contributes to the efficient transfer of chirality to the resulting product, even in the distant position of the 1,6-conjugated system [39]. For these reasons, iminium catalysis using primary amines appears to be

• , changes in the epi-amino alkaloid core of the two-component catalytic system were investigated. Introduction of the 2’-substitution to the quinine core as in AQ-2 and AQ-4 (Scheme 2) resulted in the decrease of chirality transfer providing the product with 50% and 72% ee, respectively. A similar trend was

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• structure of verrulactone A was later unambiguously confirmed by X-ray crystallographic analysis [160]. Chirality and absolute configurations remained unresolved, where it should be noted that even verrulactones A and B are axially chiral with an assumed significant racemization barrier. At least it has

• ]. Isoaltenuene (55), the 4a-epimer of altenuene, was first isolated from Alternaria alternata [260]. Its proposed structure including its relative configuration was determined by NMR spectroscopy and unambiguously confirmed by total synthesis of the (+)-enantiomer [249]. Whenever the chirality was determined, it

• was either isolated as (−)-enantiomer (from A. alternata) [250], as the (+)-enantiomer (from unidentified freshwater [251] or marine [261] fungi), or as the racemate (from Nigrospora sphaerica, A. alternata, and Phialophora sp.) [162]. It was further isolated without specification of the chirality

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• cyclophanyl-imidazole-based library of ligands. The synthesis of ligands based on the [2.2]paracyclophane (PCP) moiety, thanks to its structural features and inherent planar chirality upon selective substitution, has been recently reviewed by the same author [46]. Starting from 4-formylcyclophane 37, a GBB

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• possibly due to greater dispersive and lesser repulsive forces for larger halogens. This finding may prove useful in catalyst design where close spatial proximity of the substrate to other important structural information (i.e., chirality) has an impact on selectivity. Our analysis of selected XB complexes

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• preclude chirality as in the transformation of a prochiral molecular entity into a chiral one [1]. It is a powerful and elegant strategy in asymmetric synthesis [2], which combined with the use of chiral ligands and transition-metal catalysts enabled many valuable transformations to increase molecular

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• enantioselectivity with a cis configuration at position 5 relative to position 2. Additionally, when mixed configurations were present at position 2 in tridentate ligands (Ib and IIb), the 2R configuration facilitated more effective chirality transfer. Substituting the pyridine moiety with an imidazole in ligands

• pyridine to imidazole lowered the reaction rate but did not alter the critical role of configuration at position 2 in determining the enantiomeric purity of the final product. Furthermore, the study of “proline-type” derivative IV underscored the importance of position 2 in chirality transfer, although

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• signals in the low-range visible/NIR region. Upon protonation of the pyridine, the conformation switch leads to a spatial separation of the active Pt moieties and a release of the guest (Figure 4). Also, the same group demonstrated the induction of chirality and fluorescence with chiral guest molecules

• using a similar principle [24]. The protection from the solvent of the intercalated Pt guest enables its fluorescence emission and is accompanied by the induction of chirality in the resulting host–guest complex. A significant enhancement of the circular dichroism response of the chiral guest is

• observed confirming the formation of the host–guest complex. Again, protonation of the pyridine results in a guest release and a loss of the CD signal. Thus, this system provides a peculiar example of the control of chirality by a pH stimulus. A similar moiety employed for acid–base-triggered

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• isomerization and photochemical (only for 13a) isomerization [46]. Compounds 13 showed intrinsic planar chirality and their enantiomers could be separated by HPLC. Notably, upon thermal and photochemical isomerization of these compounds, no Z-isomers were detected and only the racemization took place. Such

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• may not be apparent at a glance. Nevertheless, comprehensive computational analyses employing the matrix method suggest that the intense long-wavelength CD signal observed for 56 is due to the coupling of individual helicene-to-TCBD electric-transition dipole moments. The emergence of axial chirality

• . The absolute configurations of the axially chiral TCBD and DCNQ derivatives were ascertained by a comparative analysis of the experimental CD spectra against the spectra derived from time-dependent density functional theory (TD-DFT) calculations. The axial chirality was stabilized by the steric

• congestion on the surface of fullerene, with its endurance contingent upon the bulkiness of the substituent incorporated onto the fullerene core. This observation was supported by the absence of axial chirality in molecules where an additional alkyne moiety is intercalated between the C60 core and TCBD or

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• center that may act as a source of chirality. Thus, the novel compounds reported in this study represent a valuable addition to the family of neutral dithiolate ligands derived from stable nucleophilic carbenes, and we are currently investigating their coordination chemistry toward various transition

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• , both enantiomers were reported. For the control of the chirality in position 2 of glycerol, (S)-solketal (17.1) was used as starting material to prepare first the hexadecylglycerol (R)-17.2 which was converted to its enantiomer following a five-step sequence (Figure 17A). First, tritylation and

• ] but to the best of our knowledge, R. Berchtold reported in 1982 the first synthesis in large quantities with a control of the chirality at the sn-2 position (Figure 21) [116]. The synthesis starts from (S)-1,2-isopropylideneglycerol (21.1). The deprotonation of the primary alcohol with sodium amide

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• generating a complex molecular topology of 2,3-disubstituted indoles bearing both axial and central chirality. The aza-Friedel–Crafts reaction would allow the nucleophile to selectively attack the C=N plane of the electrophile as directed by a triple hydrogen-bonded complex between the catalyst and the

• aryl moieties. For this purpose, sterically bulky substituents need to be present in the aryl ring attached to the C3 position of the starting indoles. The axial chirality was attributed to ester and phenolic OH groups at the ortho-positions of the aryl ring and an additional phenolic OH functionality

• electrophilic substitution also gave a quaternary aza-stereocenter in the pyrazolone moiety. Axial chirality associated with central chirality in the product structures was influenced by chiral phosphoric acid catalyst P23. To freeze the C–C bond rotation, the pyrazole moiety in 99 required sterically demanding

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• ], and nanoribbons [19]. Meanwhile, to modulate the properties of synthetic hydrocarbon NGs, a variety of heteroatom-doped NGs have been constructed [8]. Chirality is a fundamental phenomenon in nature and plays an important role in science, especially in living systems. The chirality in chemistry refers

• [20][21][22][23][24]. Currently, there is a great interest in the introduction of chirality into large conjugated polyaromatics to obtain chiral NGs with chiroptical properties. Among these chiral NGs, helicenes represent the dominant chiral compounds by virtue of their inherent helical chirality [25

• introduced as a linker, an optically pure chiral NG synthesis was accomplished using the same synthetic route by starting with an enantiopure helicene. Except for the helicene-based chirality, chirality stemming from a chiral axis is relatively rare in designing chiral NGs. Notably, Martín and co-workers

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• imines or their synthetic equivalents. Furthermore, we wanted to develop an enantioselective and diastereoselective process without adding chirality elements within the reagents. For our initial studies, we have selected the well-studied cyclic enones as substrates and the Taniaphos ligand (L14) that has