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

• groups) with little [73], if any, transition-state binding [36][80][81]. Thus, these macrocycles depend on the catalytic concept of organization; polarization is a minor contributor. Size-exclusion and regioselective outcomes are possible [56][82][83][84][85], and symmetric arrays of chiral units (like

• catalysis [229]. Methods to study the structural detail of catalysis in frameworks remain limited, and crucial techniques like solution-phase NMR are rarely useful [22]. Enzyme encapsulation [230], and electro- and photocatalysis are known [228], and chiral and low symmetry MOFs are an exciting avenue

• , although the synthesis and characterization (particularly crystallization) of low-symmetry structures remains challenging [227][231][232]. Likewise, COFs hosting chiral organocatalysts are known (Figure 6B) [226][233]. Frameworks are well-suited to hosting opposing reactive functionalities (e.g., acids and

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

• ether-type chiral auxiliary group for protection of the hydroxy group in the C-2 position was devised by Boons et al. in 2005 which opened a new avenue in oligosaccharide synthesis. Auxiliary group indicates a substituted ethyl protection which has a nucleophilic centre that can donate electrons in the

• tartgeted reaction [148]. A proper modulation of the stereochemistry of the chiral auxiliary group allows to obtain both the 1,2-cis and 1,2-trans stereoselective glycoside product (Scheme 17) [149]. An O-2 chiral auxiliary group in the glycoside donor interacts with the anomeric carbon to produce a decalin

• 1,2-cis decalin 101 facilitating the formation of 1,2-trans glycosidic product 102. This protocol was further demonstrated successfully by the same research group by using the easily available R and S enantiomers of the first-generation chiral auxiliary, ethyl mandelate. Similarly, a (1S)-phenyl-2

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• , the Chang group elegantly unveiled a protocol for an enantioselective C–N bond formation, introducing δ-lactams from dioxazolones using a copper(I) catalyst and a chiral BOX ligand [74]. As shown in Scheme 2, dioxazolones containing aryl and heteroaryl groups were converted into the corresponding

• amidation process of dioxazolones. Dioxazolone 1 binds to the chiral copper complex 3, generating the adduct INT-1. Decarboxylation then occurs, forming the copper nitrenoid intermediate INT-2, subsequently undergoing hydrogen atom transfer in a regioselective manner to afford INT-3. The related acyl

• nitrenoid intermediate was characterized by the same group [75]. Further radical rebound from INT-4 induces the enantioselective C–N bond formation. Finally, the desired product 2 is released from INT-4, regenerating the active chiral copper species to participate in the catalytic cycle. 1.2 C(sp2)–H

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

• ][22][23][24]. Moreover, copper-catalyzed asymmetric radical cross-coupling has advanced significantly over the past decade [25][26][27], with notable examples including Liu and Stahl’s enantioselective cyanation of benzylic C–H bonds using a Cu/chiral bisoxazoline catalyst [28], along with the Peters

• enantioselective C–H alkynylation of ferrocene carboxamides with terminal alkynes by using Cu/BINOL and an electrocatalytic system (Figure 5) [49]. 8-Aminoquinoline-assisted C–H functionalization provided planar chiral ferrocenes with high yield and enantioselectivity. This reaction can be applied to a wide range

• asymmetric C(sp3)–H alkynylation of tertiary cyclic amines by merging Cu(II)/TEMPO catalysis with electrochemistry to yield chiral C1-alkynylated tetrahydroisoquinolines (THIQs) (Figure 5) [50]. As a co-catalytic redox mediator, TEMPO plays an essential role in the formation of iminium intermediate 15 and in

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• -methylthiazole-2-carboxaldehyde as chelating agent, in the presence of copper triflate and the chiral diamine ligand 28. The stereoselectivity was directed by the formation of a proposed catalyst complex 29 involving two molecules of Schiff base (Scheme 22) [39]. The three-component annulation of aldehydes

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

• becoming increasingly relevant also in medicine. Many axially chiral compounds are important as catalysts in asymmetric catalysis or have chiroptical properties. This review overviews recent progress in the synthesis of axially chiral compounds via asymmetric organocatalysis. Atroposelective

• organocatalytic reactions are discussed according to the dominant catalyst activation mode. For covalent organocatalysis, the typical enamine and iminium modes are presented, followed by N-heterocyclic carbene-catalyzed reactions. The bulk of the review is devoted to non-covalent activation, where chiral Brønsted

• ; 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

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• slight decrease observed for 5ac, with chiral (R)-1-((1-phenylethyl)amino)-1,2-benziodoxol-3-(1H)-one (2c), can be attributed to potential steric hindrance induced by the methyl group attached to the benzylic carbon, which may hinder the nucleophile’s access to the electrophilic center of the HIR. The

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• ] in combination with tunable absorption and emission of visible light. Polar nematic phase [23] and chiral columnar phase materials [24] based on polar fluorobenzene rings have also recently emerged as interesting new classes of fluorous materials, revealing their enormous potential in the high-tech

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• -heterocycles using various catalytic systems such as chiral metal catalysts, chiral Lewis acids or chiral organocatalysts. This review presents an overview of the recent advances in enantioselective cyclization reactions of 1-azadienes catalyzed by non-covalent organocatalysts. Keywords: α,β-unsaturated

• covered in this review are hydrogen-bond donors such as thioureas and squaramides, Brønsted bases such as tertiary amines, and Brønsted acids such as chiral phosphoric acids. As depicted in Figure 4, a bifunctional squaramide is able to activate both an α,β-unsaturated imine through hydrogen bonding with

• the squaramide moiety and a nucleophile through deprotonation as Brønsted base. On the other hand, a chiral phosphoric acid provides a confined chiral environment where the reactants are approached, activating both the azadiene by interaction with the acidic hydrogen and a dienophile bearing a

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• of psammaplysin A remained ambiguous for approximately 30 years but was determined in 2015 by Kurtán, Garson, and co-workers through a comparison of experimental and calculated electronic circular dichroism data, as well as a method employing Trost's chiral anisotropic reagents [6]. More recently

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

• 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

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• formed. The use of a chiral aryl iodide was tested, which gave products with low enantiomeric excess. However, these preliminary trials represent the first example of a catalytic, enantioselective HVI-mediated fluorocyclisation. The authors proposed a mechanism (Scheme 4) for this reaction that involved

• from the styrenyl starting materials is stereoselective, giving the syn-diasteroisomer in high yields. A chiral iodoarene catalyst 16 was employed, along with a stoichiometric sacrificial oxidant, to give good to excellent levels of enantioselectivity. This elegant strategy led to a variety of β

• aminofluorination using BF3·Et2O with a chiral aryliodide 16 catalyst (Scheme 20) [44]. The study successfully obtained various chiral fluorinated oxazine products 38 with high enantioselectivity (up to >99% ee) and diastereoselectivity (up to >20:1 dr). Control experiments showed that using Py·9HF or Et3N·3HF as

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

• enantiomeric excess (ee) up to 5.5% [70]. Related catalytic systems based on amphiphilic 5-(cyclic-secondary-amine)-10,15,20-tris(4-sulfonatophenyl)porphyrin macrocycles 58–61 act as switchable organocatalysts for Michael and aldol reactions in water [68][69]. The macrocycles 58–61 containing different chiral

• hypothesis that the reaction would work in acidic environment using catalysts insensitive to pH-induced aggregation. In the same aldol reaction, using of macrocycles 60 and 61 containing chiral secondary amine moieties provided not only good yields, but also good diastereoselectivities; chiral HPLC analysis

• organocatalysis can be summarized in the following statements: (1) using highly distorted nonplanar macrocyclic systems with an easy access to inner –NHs and basic imine moieties (by Senge, Hill, and co-workers [61][62][63]), (2) using monomeric and aggregated forms of achiral/chiral planar amphiphilic porphyrin

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

• ; Introduction Enantioenriched α-allenic alcohols are an important class of chiral building blocks used for the chemical synthesis of biologically relevant molecules [1][2][3][4][5]. Their strength comes from the rich synthetic versatility [6][7][8][9] and biological relevance [10] of the allene functionality

• . Accordingly, the development of efficient access to optically active chiral α-allenic alcohols continues to be of significant interest in organic chemistry [11][12][13]. The asymmetric catalytic addition of allenylation reagents to aldehydes provides direct access to chiral α-allenic alcohols in an

• stable allenyltrichlorosilane that affords undesired homopropargylic alcohols [35][36] (Scheme 2b). Furthermore, Iseki [35] and Nakajima [36] evaluated only one chiral catalyst in their independent studies (i.e., no catalyst structure–reactivity and selectivity relationship study). In this context, we

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• ., the type of alkylmalonate it incorporates into a growing PK intermediate [61]. Furthermore, Xiang et al. reported recently that the stereochemistry of each new chiral center resulting from each alkylmalonate BB incorporation can be predicted based on the corresponding ketoreductase domain sequence [83

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

• from the chiral nature of the CD molecule, and its behavior fits well with the theoretical consideration. As comprehensively described [32], CD-based rotaxanes are typically synthesized by two methods: (1) the end-capping method (route a1, a2) in which the formation of a pseudorotaxane structure first

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• formation of peroxide 9. The enantioselective peroxidation of alkenes 10 with TBHP with the formation of the optically active products 11 was carried out in good yields and low ee by the use of in situ-generated chiral bisoxazoline–copper(I) complexes (Scheme 7) [43]. Studying the oxidation of α-pinene (12

• . The oxidation of benzyl alcohol 62 with TBHP results in aldehyde C, HAT from which by tert-butoxy radical A leads to the C-centered radical D. Subsequent recombination of radicals D and B provides the target product 63. An enantioselective peroxidation method of alkylaromatics with TBHP using chiral

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

• Darmstadt, Germany Institute of Materials Science, Technical University of Darmstadt, Peter-Grünberg-Str. 2, D-64287 Darmstadt, Germany 10.3762/bjoc.20.246 Abstract Two racemic anti-4,6-diphenyl-5,5-difluoro-1,3-dioxanes were prepared and the corresponding enantiomers were evaluated as potential new chiral

• 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

• chemistry [1][2][3]. In particular, cholesteric, i.e., chiral nematic, liquid crystals (LCs) are attractive for many display applications due to their chiroptical characteristics as well as the selective reflection of light giving rise to Bragg interference colors [4]. Cholesteric LCs can be obtained either

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

•  1a, 1, 2) [10][11][12], liquid crystals (Figure 1b, 3, 4) [13][14][15][16][17], fluorescence materials (Figure 1c, 5) [18][19], and so on, have been developed in recent years. In sharp contrast to the major development of such non-chiral tetrafluoroethylenated compounds, there have been only few

• reports on the preparation of chiral molecules possessing a tetrafluoroethylene unit on an asymmetric carbon center in a high optical purity, and to the best of our knowledge, only the following have been published so far (Scheme 1). As a highly enantioselective synthesis, there has been a pioneering work

• by Linclau et al. They have reported that the asymmetric Sharpless dihydroxylation of readily available (E)-5-bromo-4,4,5,5-tetrafluoro-2-penten-1-ol derivative 6 led to the corresponding chiral diols 7 with an excellent enantiomeric excess, 96% ee (reaction 1 in Scheme 1) [20][21]. It has also been

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

• 350100, China 10.3762/bjoc.20.232 Abstract The catalytic (asymmetric) allylation and propargylation have been established as powerful strategies allowing access to enantioenriched α-chiral alkenes and alkynes. In this context, combining allylic and propargylic substitutions offers new opportunities to

• ). Further control experiments and DFT calculations show that during the catalytic process, tertiary amine directly participates as a nucleophilic reagent to give the ammonium salt, which then releases dimethylaminium to provide the final product (Scheme 12). Chiral allylic sulfone compounds can be easily

• -, stereo-, and enantioselectivities, resulting in a series of chiral yne-allylic sulfone compounds with different substituents (Scheme 13, 14a–q). Due to the high steric hindrance of the γ-site, nucleophilic substitutions preferentially occur at the α-site. Through subsequent control experiments, they

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• easily recovered by precipitation using polar solvents. This catalyst proved to be excellent for the preparation of (S)-baclofen on a gram scale, furnishing the main chiral intermediate in high yield and enantioselectivity. Furthermore, the catalyst was recycled over five cycles while maintaining its

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

• into readily available substrates such as epoxides, resulting in the formation of polycarbonates or monomeric cyclic carbonates [22]. Depending on the substitution pattern in the epoxide, a chiral centre is present in the product. The insertion of CO2 into epoxides has been the subject of numerous

• an asymmetric FLP and consequently an asymmetric catalyst. The subsequent study explores the asymmetric insertion of CO2 into chiral PO catalysed by the proposed in silico designed catalyst. Computational Details During the benchmark to choose the best catalyst, the reported geometries were optimised

• results, we looked into the literature to explore examples of asymmetric FLPs. This exploration revealed three main types, namely, intramolecular chiral FLPs, intermolecular FLPs composed of a chiral acid and an achiral base, and intermolecular FLPs comprising an achiral acid and a chiral base [61][62

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

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• product (Scheme 34). To date, only a few enantioselective reactions using metal catalysis and electrochemistry have been reported. Very recently, Ackermann and coworkers employed Co(OAc)2 as a catalyst and a salicyloxazoline derivative as a chiral ligand to achieve the electrochemical atroposelective C–H

• annulation of benzamides and allenes [47]. This method demonstrated excellent functional group tolerance, yielding a broad range of C–N axially chiral compounds with good yields and enantioselectivities. The practicality of this strategy was further demonstrated by a decagram-scale synthesis and the LSF of

• efficiently, enabling the LSF of benzodiazepine drugs such as diazepam, halazepam, and prazepam. Mechanistically, the Rh complex activates the C–H bond in phenylpyridine and assists in forming a bond with diphenylphosphine oxide, which, after anodic oxidation, yields the target product (Scheme 39). A chiral