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

• product was obtained in moderate diastereo- and enantioselectivity, however, chloronium salt 9c did not show significant catalytic activity, and the product was formed in nearly the same yield as that obtained without a catalyst with low stereoselectivity. From these observations, bromonium salt 9a was

• (Table 1). Solvent screening was carried out, and it was found to strongly affect the product’s stereoselectivity. Non-polar solvents yielded better results, and toluene was found to be optimal (Table 1, entries 1–6). Polar solvents such as acetonitrile prohibited halogen bonding between 9a and the

• reaction; the stereoselectivity of product 17j drastically dropped. The scope for the pre-nucleophile showed that phenyl-substituted 16b provided 17k in 94% yield with high diastereoselectivity, albeit with decreased enantioselectivities. Methyl ester 16c and tert-butyl ester 16d were also applied to the

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• crystalline compounds significantly enhances the stereoselectivity and yield of topochemical reactions compared to those conducted in solution [10]. A key requirement for these reactions is the intermolecular distance between the two reactive double bonds. Schmidt’s rule, which governs topochemical [2 + 2

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• -Michael (ReM) reaction occurs, its enantio- and diastereoselectivity, and the influence of different experimental parameters on its scope and stereoselectivity. The reaction was studied on a 1:2 mixture of the racemic diastereoisomers syn-1 and anti-1 (prepared according to our previous protocol) [25

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• ://creativecommons.org/licenses/by/4.0). Photomechanochemical control over stereoselectivity in the [2 + 2] dimerization of acenaphthylene. The photo in Scheme 9 was republished with permission of The Royal Society of Chemistry, from [75] (“Photomechanochemical control over stereoselectivity in the [2 + 2

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• insufficiently studied furo[2,3-f]isoindole derivatives. Ugi adducts formed from (E)-3-(furan-2-yl)acrylaldehyde, maleic acid monoanilide, isonitrile, and an amine spontaneously underwent the IMDAV reaction with a high level of stereoselectivity, leading to single pairs of enantiomers of 4,4a,5,6,7,7a-hexahydro

• investigate the possibility of obtaining related compounds in the Ugi/IMDAV reaction. It was found that the reaction of (E)-3-(thiophen-2-yl)acrylaldehyde proceeds similarly to furylacrylaldehyde and with a high level of stereoselectivity, forms a single pair of enantiomers of 4,4a,5,6,7,7a-hexahydro-3aH

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

• exhibits comparatively less efficacy in achieving complete stereoselectivity in the glycosylation reactions. Remote participation is a still highly debated topic in the scientific community. However, implementing the participating role of the remote groups in glycosylation reactions is widely practised to

• carbohydrate moieties [20][21][22] coupled with the need for suitable anomeric stereoselectivity [23]. Over the decades, there have been widespread studies to standardise and optimise glycosylation reactions, but a standard reaction protocol still eludes the scientific community. We will give a generalised

• protecting groups as remote groups and analyse the various critical viewpoints pertaining to their distal contribution in determining the stereoselectivity of the glycosylation reactions. The comprehensive knowledge of the role of the protecting groups in glycoside reactions in the different positions

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

• standard conditions. Subsequently, radical-polar coupling between electrophilic Ni-bound α-carbonyl radical intermediate 45 and remaining nucleophilic Cu-enolate 44 provides a chiral product 42 containing vicinal quaternary stereocenters with high stereoselectivity, and all three possible stereoisomers of

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

• and sulfur dioxide afforded vinyl sulfones with excellent regio- and stereoselectivity (Scheme 9) [22]. The authors used DABCO(SO2)2 to generate sulfur dioxide, and visible light irradiation and the mandatory presence of a photocatalyst for this transformation suggested a radical mechanism. The

• -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

• stereoselectivity (96% ee, >95:5 dr). No racemization was observed after 36 hours at 150 °C in o-xylene. The asymmetric synthesis of arylindolylindolinones 139 or 141 bearing both central and axial chirality was accomplished by a combination of arylindoles 137 or 140 and indolinones 138 with CPA (R)-C22 acting as

• . Experiments determining the configurational stability were done in both toluene at 120 °C and o-xylene at 150 °C for up to 36 h with retained stereoselectivity but decreasing yields at higher temperatures for prolonged periods of time. The possible activation mode explains the stereocontrol of the reaction

• intermediate Int-53. Control experiments confirmed that this structure could undergo successive reduction and oxidation through intermediate Int-54 to give benzylimine intermediate Int-55. Alternatively, a direct [1,5]-H migration of Int-53 also leads to Int-55. The stereoselectivity of the product is

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

• except for azadienes bearing a bulky t-Bu substituent, which led to the Michael product 27e’ albeit with low stereoselectivity. The authors proposed a plausible reaction mechanism to explain the observed stereoselectivity of the reaction. Firstly, the isocyanoacetate is deprotonated by the tertiary amine

• . Then, an intramolecular aldol reaction leads to intermediate D which undergoes final protonation to produce the desired chiral product 43f. The authors proposed that the stereoselectivity of the Michael addition product would direct the stereoselectivity of the intramolecular aldol reaction. To

• excellent enantioselectivities (97–99% ee) using also chiral phosphoric acid XIV (Scheme 17). The authors proposed a reaction mechanism in order to explain the observed stereoselectivity of the products in which through hydrogen bonding the chiral phosphoric acid provides a chiral environment where the

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

• the ester function, as previously reported [32][33][34][35]. The corresponding adducts 5a–f were isolated with good yields from 66 to 88%. In the case of hydrazides 5e and 5f, the mixture of diastereomers (1:1 ratio) could not be separated at this stage. Although no stereoselectivity is observed, it

• 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

• stereochemistry of the reaction. Linear chiral catalysts were found to offer higher stereoselectivity compared to spiro-catalysts. Under optimized conditions, the asymmetric aminofluorination of N-cinnamylbenzamides 37 using BF3·Et2O as the fluorine reagent demonstrated good yields and high stereoselectivity

Tunable full-color dual-state (solution and solid) emission of push–pull molecules containing the 1-pyrindane moiety

• Anastasia I. Ershova,
• Sergey V. Fedoseev,
• Konstantin V. Lipin,
• Mikhail Yu. Ievlev,
• Oleg E. Nasakin and
• Oleg V. Ershov

Beilstein J. Org. Chem. 2024, 20, 3016–3025, doi:10.3762/bjoc.20.251

• containing various numbers of substituents at the donor site, which differed in their electron-donating strength, was obtained. It was found that the reaction of pyridine 2 with aromatic aldehydes occurred with complete stereoselectivity – only the E-isomer was obtained as the reaction product. The

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• , we observed a striking illustration of this phenomenon. A Michael addition involving gem-difluorovinyl and trifluorovinyl acceptors was successfully achieved, demonstrating high stereoselectivity. This selectivity was further elucidated through theoretical calculations. Using this methodology, a

• products. These highly stable compounds were isolated after purification on silica gel in good yields (Scheme 2) and characterized by spectroscopic methods. The reaction proceeded with very high Z-stereoselectivity (Scheme 2, compounds 9a–d). In the 19F NMR spectra of crude mixtures, only trace amounts of

• remarkable stereoselectivity, a finding elucidated by DFT analysis. These results mark significant progress toward the synthesis of novel fluorinated building blocks. Our team is currently exploring the application of this methodology to amino acid substrates, aiming to contribute further to the burgeoning

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

• , including di- and trisubstituted ones, were well tolerated in the reaction, providing products 24 with good stereoselectivity in moderate to good yields. Moreover, the reaction was successfully conducted with various substituted vinyl pinacol boronates and di(4-tolyl)iodonium triflate, resulting in moderate

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

• developments and illustrates the influences of copper salt, ligand, and substitution pattern of the substrate on the regioselectivity and stereoselectivity. Keywords: copper-catalysis; copper vinyl allenylidene intermediate; 1,3-enyne; 1,4-enyne; yne-allylic substitution; Introduction Copper is earth

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

• adduct with a relative free energy of 0.7 kcal·mol−1. Thus, the evaluation of the stereoselectivity of the designed catalyst was conducted by only studying the steps after the capture of CO2 by the catalyst. The reaction occurs in two steps (Table 1). Initially, a pre-TS assembly, with the PO compound

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

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• the diastereoselectivity of the nucleophilic attack of the β-lactam on the radical cationic intermediate was influenced by stereoelectronic factors. Compounds unsubstituted at position C-3 of the β-lactam ring, 11d–h, showed modest stereoselectivity with a higher dr (6.7:1) for compound 11d, which has

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

• high stereoselectivity were similarly recorded for the other substrates 2c and 2d possessing different Rf groups at the 3 position (Table 2, entries 1–3). Mixing of 2b with different primary (entries 4–7 in Table 2) and secondary (entries 8 and 9) amines led to the formation of the respective products

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

• selected recrystallised products showed 98–99% ee. Importantly, both silane and stannane-based protocols were successfully performed on a 5 mmol scale using substrates 52 and 59. There was a slight loss in yield and a negligible decrease in stereoselectivity in the case of 2,3-dimethylallylation product 52

• . The limitations in the scope of this methodology include a poor stereoselectivity achieved with 5-membered cyclic 2,3-disubstituted silanes in contrast to the 6-membered analogues (53). A lower efficiency was recorded with 2-substituted allylsilanes bearing either a halogen or an alkyl group with

• the aromatic group of the substrate had a significant contribution to the stereoselectivity of the reaction. The reaction demonstrated a broad scope both in the acetal 98 and in the allylsilane (Scheme 20). A high enantioselectivity was achieved even with the non-aromatic 1-cyclohexene-1

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

• Technology, wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland 10.3762/bjoc.20.198 Abstract The study presents a novel approach utilizing iminium salt activation and mild enolization of thioesters, offering an efficient and rapid synthesis of Michael adducts with promising stereoselectivity and marking a

• products with 61% and 63% yield in the solution and mixer mill, respectively. However, the drop of stereoselectivity was noted in comparison to the reaction in toluene (94% ee vs 86% ee in mixer mill, ∆ee = 8). It should be noted that the dibenzyl malonate remained inactive for subjecting to reaction under

• Information File 1). However, the low stereoselectivity is not surprising. The analysis of the covalent adduct of cyclopentenone with amines may result from the “flattened” of the small system that renders them less sensitive to steric interactions generated by the catalyst compared to cyclohexenone [42][43

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• the support [8][67]. Adsorption is a non-covalent reversible technique for attaching organocatalysts to supports. It offers a facile and modular construction of immobilised chiral catalysts with maintained or even improved activity and stereoselectivity [68][69][70]. The main advantages of catalyst

• -nitrostyrene, the recyclability of the organocatalyst in the betaine/sorbitol/water DES system was demonstrated up to 10 cycles without any significant decrease in yield (up to 99%) or stereoselectivity (up to 96% ee). Encapsulation is an irreversible method and the only catalyst immobilisation process that

• support can lead to lower stereoselectivity, as previously shown in Scheme 4. Solutions for limitations of solid-supported organocatalysts The properties and applicability of an immobilised catalyst depend not only on the immobilisation method and the physicochemical characteristics, porosity, and

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

• reported in due course. Biologically active derivatives of cyclohexanones. X-ray structure of 4a (CCDC 2351387). Origin of stereoselectivity in the double Michael addition. The Michael donor–acceptor reactivity of curcumin: previous vs present work. A plausible reaction mechanism. Scale-up reaction

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• ; this reaction is catalysed by S-adenosylmethionine (SAM or AdoMet)-dependent methyltransferases (MTs). These enzymes are known for their excellent chemo-, regio-, and stereoselectivity [3][4][5][6]. Their ability to introduce methyl groups at specific positions within ribosomal peptides equips the

• . Additionally, stereoselectivity can be achieved by using potassium bis(trimethylsilyl)amide for deprotonation and methylation with MeI [33][39]. Any of these routes would yield methylated amino acids that can then be incorporated into an oligopeptide in solid-phase peptide synthesis (SPPS). Additionally, N