Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• phenol delivered 1,2-naphthoquinone 106. Notably, enantiomer (−)-106 could be prepared from (+)-105, which was in turn obtained by preparative HPLC on a chiral stationary phase from (±)-105. Following extensive screening, it was found that photoirradiation of quinone (−)-106 under the optimized

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• both in pure form from only one enantiomer of a chiral starting material or a chiral ligand [33]. To demonstrate the value of our protocol in this regard, an enantiodivergent synthesis of isochaetominine (10) was envisioned. Previously, we have reported a four-step synthesis of (+)-isochaetominine (ent

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• proposal is that toussaintine C was isolated as a racemic mixture, and sarglamides A and B are derived from one enantiomer of toussaintine C while sarglamides C–E are derived from the other one. The Diels–Alder cycloadditions are basically proceeded through endo-selectivity. The isopropyl group in α

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

• high enantioselectivity. However, since an enzymatic reaction generally produces only one of the two enantiomers, extensive enzyme screening is often required to access the desired enantiomer. Among various types of enzymes, lipases have proven to be efficient for the desymmetrization of 1,3-diols

• genus) are generally operated in mild conditions achieving relatively high yield and enantioselectivity. However, due to the intrinsic structural limitations of lipases, accessing the desired enantiomer requires laborious screening of enzymes. In the case of transition-metal-catalyzed acylations, the

• enantioselective desymmetrization of prochiral 1,3-diols within complex structures can be realized using organometallic catalysts composed of copper or zinc salts and different types of chiral ligands. In general, the ability to control the stereoselectivity of the product by using the enantiomer of the ligand in

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

• with a Daicel Chiralpak IF column (Figure S1, Supporting Information File 1). The absolute configuration of the separated enantiomers of MC1 was determined based on the calculated CD spectra (Figure S4, Supporting Information File 1). The first fraction was defined as the (+)-enantiomer, and the second

• fraction was assigned as the (−)-enantiomer. As shown in Figure 5, the CD spectra displayed mirror images with positive and negative Cotton effects at wavelengths from 250 to 500 nm, indicating strong chiroptical responses. (+)-MC1 shows five positive Cotton effects at 259, 305, 355, 392, and 453 nm, as

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

• for accessing chiral compounds. Starting from racemic starting materials, this method entails selective conversion of one enantiomer facilitated by a chiral catalyst, yielding enantioenriched products and allowing for the recovery of unreacted substrate with a high level of enantiopurity [24][25

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

• ) observed in their single crystals. Results and Discussion Synthesis of quinoline-2-ones (thione), their enantiomer separation and rotational stability We focused on N-(2-halophenyl)quinolin-2-ones 1 and the thione analogue 2 as alternative substrates to verify chirality- and functional group-dependent

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

• become quite attractive structural motifs in drug design [13][14]. A few examples are shown in Figure 3: oxetano-thalidomide 1 was designed as an analogue of the infamous thalidomide to block racemisation and hence prevent the severe side-effects caused by the opposite enantiomer [15]. Compound 2 is a

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• . Similarly, the enantiomer (S)-118 was esterified with o-DPPB under the same conditions, providing (S)-120 in 88% yield (>99% ee, E/Z >99:1) after recrystallization. The authors noted that both (R)- and (S)-120 could be stored in their crystalline forms for months without significant decomposition or

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• ). Other rare-earth salts, including Y(OTf)3, La(OTf)3, Sm(OTf)3, Tb(OTf)3, Er(OTf)3, and Lu(OTf)3, were also screened, but no better results were observed (Table 1, entries 6–11). In addition, different ligands L2–L4 were evaluated (Table 1, entries 12–14). The enantiomer of product 3aa was obtained in 28

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

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• achieved selective synthesis of either enantiomer of a target product by controlling the reaction duration (Scheme 13) [42]. When performing the asymmetric intermolecular allylic amination of 6-hydroxyisoquinoline (49) with tert-butyl(1-phenylallyl)carbonate ((rac)-50) using an Ir catalyst derived from [Ir

• in the absence of a Brønsted acid additive, the opposite enantiomer 52 was obtained. Mechanistically, an initial kinetic resolution (KR) of (rac)-50 occurs via an Ir-catalyzed asymmetric allylic amination. Due to the higher reactivity of (S)-50, it reacts with 6-hydroxyisoquinoline within 6 minutes

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

• unaffected (87–89% ee (R-enantiomer), entries 1–3). Because we assumed complex 6 (with two bidentate phosphate ligands) to be a precursor to the actual catalytically active species, we pre-formed it, following the procedure employed to prepare achiral complex 4 (with two monodentate phosphates, Scheme 1) and

• industrial production (Table 2, entries 4, 8, and 9). All these experiments gave only low ee values (4–19% ee, Table 2, entries 4–9), with a preference for the S-enantiomer. Use of aromatic alcohol or (R)-1-phenylethanol as additives did not improve either yields or enantioselectivities (Table 2, entries 5

• hydrazone isomers give the same hydrocyanation product and with low ee, because pathways with opposite preference for either product enantiomer mix via internal rotation TS8, which explains also the low enantioselectivity observed in our experiments and with preformed pre-catalyst 6. Which absolute

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• – anionic, Lys – cationic, Leu – hydrophobic) affects their binding by the receptor. Additionally, to probe whether the chiral glucose backbone of the receptor allows to achieve selective binding of one enantiomer of tryptophan over the other we used both ʟ- and ᴅ-tryptophan as guests. The binding of amino

• towards ʟ-Trp over its ᴅ-enantiomer (entries 1 and 6, Table 1). Since tryptophan fulfills many of its biological functions as a component of peptides and proteins [2][3][4][5], we also probed, if 1 can recognize tryptophan residues within peptide sequences. For this purpose, we prepared six model

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

• chromatography [1]. Sometime later, kinetic resolution (KR) emerged. This method is based on the different reaction rates of each enantiomer in a racemic mixture when they are reacted with a reagent, a chiral catalyst, or an enzyme. This process results in obtaining the less reactive enantioenriched enantiomer

• catalyst or the bistrifluoromethyl-substituted analog B could enable the retro-Michael reaction of only one enantiomer of the racemic mixture, potentially leading to a kinetic resolution of the 1,5-dicarbonyl compounds (Scheme 2). Results and Discussion An initial attempt was made to determine if the retro

• , enantioselectivity increased until a specific time, and after that, the enantiomeric ratio decreased (compare entries 1–3 and 21–23 in Table 1). The interesting result is that the major enantiomer in the enantioenriched mixture is now the opposite of the one obtained when the ketone and the α,β-unsaturated aldehyde

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

• acidic hydrogen of the CPA promotes dehydration and the formation of the vinyliminium intermediate. Chirality control is consistent because of the retarded reaction with the unfavored enantiomer of the bisindole 142 and its low rotational barrier resulting in quick exchange between the two. Products 147

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

•  19) [70]. According to the screening studies, a mixture of enantiomers was obtained, with one enantiomer predominating (95 to >98% ee) under the optimized conditions. The phenyl with electron-deficient groups is well tolerated and produces outstanding yields. Moreover, the phenyl with a bulky

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• )-enantiomer of 5e and therefore, these compounds were classified as inactive. The docking results are shown in Table 3. Compounds 4a–e bind to the active site of CYP51 with affinities ranging from −7.7 to −8.8 kcal/mol and compound 5e has a much higher affinity of −5.4 kcal/mol. Therefore, we assume that the

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

• strategically modifying LB substituents to induce asymmetry, a stereoselective catalytic scaffold was developed, favouring one enantiomer from both epoxide enantiomers. This work advances the in silico design of FLPs, highlighting their potential as asymmetric CCU catalysts with implications for optimising

• –CH(CH3) bond. Additionally, the (S)-epoxide enantiomer was employed consistently. Symmetric FLP scaffolds – achiral environment Following the initial exploration and preliminary results, our attention shifted toward the identification of a suitable catalyst. Drawing inspiration from the literature

• was engineered to produce a single enantiomer preferentially from both enantiomers of the epoxide substrate. An enantiomeric excess of 95%ee was initially achieved, with the predominant (R) enantiomer. Enhanced selectivity was subsequently observed through additional transition states, resulting in a

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

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

• -imine is activated either with a Brønsted or Lewis acid. In both cases, the allyl group of the silane reagent 46 attacks from the Re-face of the imine, leading to the major (R)-enantiomer of 47. Based on the experimental data obtained with the preformed silylated catalyst and preformed imine, the Lewis

• absolute configurations of homoallylamines 66 were assigned by analogy to 67, the configuration of which was determined after removal of the N-aryl group and comparing the optical rotation with the literature values for the known enantiomer (S)-69 (Scheme 14). The proposed stereochemical model suggests

• employing chiral Brønsted acid catalyst (S)-TRIP (118) (Scheme 25). In this approach, the racemic β-formyl amide forms the iminium intermediate that undergoes fast equilibration via the enamine tautomer to form preferentially one enantiomer which then undergoes the acid-catalysed aza-Cope rearrangement

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• develop a comprehensive model, finding that imine parameters govern the defining transition state and hence the preferred enantiomer. In a focused modelling, two separate models are constructed, one for all E- and Z-imines, respectively, finding substrate–catalyst matching is important for E- and Z-imines

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• (Figure 14) [249]. While most of the investigations including the X-ray data suggested that this natural product occurs as a racemate [38][74][147][162][248][249], it was occasionally obtained as the (−)-enantiomer [250][251]. The assumption that the methyl group in (−)-altenuene has the same orientation

• ]. 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

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• a pair of enantiomers with a ratio of 9% R and 91% S using the Ohrui–Akasaka method [127]. Structurally, compound 21 represents the second example with a (R)-anteiso enantiomer in addition to nocapyrone L [128]. An antimicrobial activity assay showed that compounds 21–23 could inhibit the growth of

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• the conjugate addition product 3aa in 58–62% yield with 74% ee (Table 1, entry 1). On the other hand, 9-amino-9-deoxyepicinchonine (II) [30] furnished the opposite enantiomer ent-3aa in 62% yield and 66% ee (Table 1, entry 2). Among the screened organocatalysts (see Table S1 in Supporting Information