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

• glycochemists. The protecting building blocks on the glycosides contribute significantly in attaining the required stereochemistry of the resulting glycosides. Strategic installation of suitable protecting groups in the C-2 position, vicinal to the anomeric carbon, renders neighbouring group participation

• multistep synthesis of complex oligosaccharides and in turn, standardise the process of the glycosylation towards a particular stereochemical output. While neighbouring group participation has been quite effective in achieving the required stereochemistry of the produced glycosides, remote participation

• position as well as in a distal or remote position in the glycosyl donors, particularly concentrating on the works in the present millennium post 2000. Involvement of protecting groups in the near, proximal or vicinal position on the stereochemistry of the glycosylation reaction is termed as ‘neighbouring

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

• were tolerated, while a dioxazolone containing bromobenzene displayed lower reactivity (26c). The enamide 26d, derived from lobatamide, was successfully produced without altering the stereochemistry of the oxime ether. Terminal alkynes with linear alkyl group, protected alcohol, and sulfonamide

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

• to explain the stereochemistry of the product of the IEDADA reaction, the Si face of the azadiene should be attacked by the enecarbamate with endo selectivity, thus leading to the (4S,5R,6R)-cycloadduct 46. In 2019, as a follow-up work of their previous work, Masson and co-workers published a

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

• analysis (Figure 5). Consequently, it was possible to assess the stereochemistry of the other diastereoisomer 8f’ and their precursors 7f and 7f’. On the other hand, considering the similarities of the 1H NMR spectra of the CF2H and CF3 analogs, by comparison, we could hypothesize the absolute

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

• . The authors studied the stereo-, regio, and chemoselectivity in both cyclic and acyclic substrates. It was observed that the use of acyclic iodane reagents 19 and 20 predominantly led to products with β-stereochemistry, whereas the cyclic iodanes 21 and 22 favour pathways leading to α-stereochemistry

• 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

• is then attacked by a nucleophile. The use of chiral iodine catalysts is essential for controlling the stereochemistry of the reaction. The specific arrangement of the catalyst influences the orientation of this nucleophilic attack as supported by density functional theory (DFT) calculations. In 2022

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 chemical structure of a molecule is defined as the arrangement of its atoms and bonds, which describes not just the size and shape of a molecule, but also encompass its stereochemistry, charges, polarity, functional groups, as well as the way these elements are spatially oriented. The chemical

• ., 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

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

• E-isomer of products 9 were identified. The fluorine atom signals of 9a–d were located at approximately −112 ppm (triplets, J ≈ 27 Hz, Fβ) and at −155 to −159 ppm (multiplets, Fα). The stereochemistry was determined by 19F{1H} NMR spectroscopy. The observed coupling constants J ≈ 2 Hz between

• addition–elimination reaction, affording the corresponding fluorinated 13a–d (Scheme 4) and nonfluorinated 14a–d (Scheme 5) unsaturated products. Also this time, for compounds 13a–d, the formation of only Z isomers was observed (Scheme 4). The stereochemistry was determined by 19F{1H} NMR spectroscopy

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

• the NOESY spectrum of the imine (R)-16c, the stereochemistry of the imines (R)-16 was determined as E [36]. Among the imines thus obtained, (R)-16b was used to investigate the optimum reaction conditions (Table 1). Treatment of (R)-16b with 1.2 equiv of DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) in THF

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

• an in silico approach to design asymmetric frustrated Lewis pairs (FLPs) aimed at controlling reaction stereochemistry. Four FLP scaffolds, incorporating diverse Lewis acids (LA), Lewis bases (LB), and substituents, were assessed via volcano plot analysis to identify the most promising catalysts. By

• distance between the CH3 group in the catalyst and the epoxy carbon atom (3.45 Å vs 3.75 Å in TS_S_S), a steric clash between the two methyl groups occurs (Figure 9). This results in an inversion of stereochemistry via rotation of the epoxy C–C bond, leading to the formation of the (R) product. As two TSs

• pairs tailored specifically to control the stereochemistry of the CO2 insertion reaction. Computational evaluations of four distinct FLP scaffolds, incorporating various Lewis acids, Lewis bases, and substituents, identify the most promising catalyst candidates through volcano plot analysis. The volcano

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

• is the high regio- and stereoselectivities of its epoxy ring opening specifically occurring at the 2 position in an SN2 manner, when it is treated with appropriate nucleophiles (Nu), leading to the formation of the 2-substituted 3-hydroxyesters with 2,3-anti stereochemistry. These characteristic

• t-BuO2Li reagent [31], we speculated that NaClO·5H2O would similarly work for the corresponding Z-1 with retention of stereochemistry. The procedure found here was also applied to the three representative CF3-containing α,β-unsaturated esters,1h–j [42] with different substitution patterns (Scheme 2

• 2 were recognized as versatile building blocks for the construction of 2-amino-3-hydroxypropanoates with 2,3-anti stereochemistry, if appropriate amines work nicely in a nucleophilic manner [44]. After the brief optimization of the conditions for the reaction of 2b and p-anisidine, good yields with

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• fashion. The dissimilarity of the diastereomeric ratios from cis- and trans- starting materials indicates that the potential intermediate is too short lived for complete ablation of the starting material stereochemistry. Second, the aziridination of cyclopentene by PhINTs in the presence of a radical trap

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

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

• undergoing yet another diastereoselective 6-endo-trig intramolecular oxa-Michael addition. The structure and stereochemistry of compounds 3 and 4 were confirmed by 1H-1H-COSY and 1H-1H-NOESY NMR experiments. This was further unambiguously established by single crystal X-ray analysis of a representative

• curcumins 1 with arylidenemalonate 2 can be explained in terms of the relative stereochemistry of the substituents in the enolate arising from the first Michael addition (Figure 3). Comparison of the two possible transition states TSI and TSII for second Michael addition suggests that a severe 1,3-allylic

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• (trifluoromethyl)amine easily reacted with (Z)-1,2-difluoroethylene to form the addition product in high yield (Scheme 11) [89]. However, the stereochemistry of this reaction has not been reported. A similar reaction of (Z)-1,2-difluoroethylene with N-chloroimidobis(sulfonyl fluoride) (Scheme 12) [90] was shown to

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• two diastereomers, lying in the intervals 5.5–6.0 Hz and 1.5–2.5 Hz for the cis and trans forms, respectively [33][34]. This makes it easy to assign the stereochemistry of the products obtained. Additional confirmation was gained from X-ray analysis data for structure 3t (Scheme 2). In some cases, we

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• substrate was also examined to give a dihydroisocoumarin product 3o in high yield with moderate enantioselectivity. The absolute stereochemistry of the bromolactonization product 3o was confirmed by comparison with reported data [24]. The transformations of the optically active bromolactonization product 3a

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• activity. Synthesizing spiro heterocyclic steroids entails numerous methodologies. Although the inherent stereochemistry of steroids sometimes facilitates the production of a single diastereomer without the need for chiral auxiliaries, nevertheless, their synthesis remains challenging due to the creation

• size and type of targeted cycle, ranging from four- to seven-membered rings, and encompasses heterocycles containing oxygen, nitrogen, sulfur, and/or phosphorus atoms. In instances where the stereochemistry of the new spiro centre remains undetermined, it is omitted. Additionally, the review excludes

• centres is claimed (C-17 and C-3’). However, no indication was provided regarding their stereochemistry, yet only one stereoisomer was isolated in a pure form. Spiro steroids with five-membered heterocycles 17-Spirolactone steroids In 2000, Poirier’s group reported an efficient synthesis of a spiro-γ

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

• stereochemistry has not been fully determined yet, one of two proposed positional isomers of the biaryl link between Trp2 and Trp3 is depicted [66]. The three-dimensional structures of the conventional O-MTs OlvSA (model structure calculated by Colabfold [75] and visualised by PyMOL [76]) and LahSB with bound SAH

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• Lewis interactions from a natural bond orbital perspective. Keywords: anomeric effect; fluoropyrrolidine; gauche effect; stereochemistry; Introduction The pyrrolidine ring structure is prevalent in numerous natural alkaloids and is an important feature of the proline and hydroxyproline residues that

• pervade biochemistry in peptides and proteins. The chemical and biological properties of substituted pyrrolidine derivatives, along with many other compounds, hinge on the relative stereochemistry. It is well established that the presence of fluorine in an organic molecule can significantly influence the

• , substituted 3-fluoropyrrolidines, particularly in the form of 2-carboxy derivatives (fluoroprolines), have been extensively explored. These compounds represent valuable nonnatural amino acids, and depending on the regio- and stereochemistry of fluorine substitution, fluoroproline substututions can enhance the

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• , Figures S16–S26, Table S1). Indeed, our results support the proposed structure of ceanothine B while also assigning absolute stereochemistry consistent with all ʟ-amino acids (Figure 5). We next explored the GNPS network for new cyclopeptide alkaloids from C. americanus. We previously noted the presence

• and Leu-β is supported by HMBC correlation between Tyr-C3 (δ 156.3 ppm) and Tyr-C4 (δ120.5 ppm) and NOESY correlation between Tyr4-H (δ 7.01 ppm, 1H) and Leuβ-H (δ 4.80 ppm, 1H). Similar to other characterized cyclopeptide alkaloids, J-coupling constant (Jα-β = 8.0 Hz) supports S-stereochemistry at

• mass spectra were used to generate a GNPS network using the following parameters: 0.2 Da precursor ion mass tolerance, 0.5 Da fragment ion tolerance, and a minimum of 8 matched fragment ions. Marfey’s analysis To determine the stereochemistry of the new molecules, Marfey’s analysis was used. Standards

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• bond formation to afford the acyloxylation product was observed, and favoured when using directing groups with less steric bulk. This product had the opposite stereochemistry to the fluorination product suggesting it occurred via a competitive SN2 pathway. This is supported by the selectivity for C–O

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

• center. Under the disclosed optimized conditions, the product ent-3ba was isolated as white solid with 85% ee and the enantiopurity of the product could be enriched to 98% ee by single recrystallization. The absolute stereochemistry was determined to be “R” on the basis of single-crystal X-ray

• crystallography data of ent-3ba (Figure 2) [37]. The stereochemistry of the products in this series was assigned by analogy. Based on the observed absolute configuration of product ent-3ba and preceding literature reports [38][40], a plausible mechanistic pathway is outlined in Scheme 5. Initially, in the

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• stereochemistry. However, the reliability and applicability of these prediction methods have not been thoroughly assessed. In this study, we conducted a comprehensive bioinformatic analysis of 1,762 KR sequences from cis-AT PKSs to reevaluate the residues involved in conferring stereoselectivity. Our findings

• elongated growing chain may undergo further processing by KR, DH, and ER domains, generating β-hydroxy, α,β-alkene, and saturated β-methylene groups, respectively (Figure 1a). KR domains have garnered significant attention from researchers due to their ability to control the stereochemistry at the α- and β

• . There are also instances where KRs contain or lack both of the LDD and W motifs, making it difficult to predict stereochemistry (Figure 1c). With the increasing availability of whole genome sequencing, a growing number of PKS gene clusters and their products have been characterized [19]. To assess and

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• clearly showed that this reaction has a wide scope of substrates. The obtained compounds 4a–t have four chiral carbon atoms. The multicomponent reaction might result in several diastereomers. On the basis of TLC analysis and 1H NMR spectra of the crude products, only one relative stereochemistry was