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

• . Lipases commonly share typical sequences of α-helices and β-strands and possess a catalytic triad consisting of serine (Ser), histidine (His), and aspartate (Asp) or glutamate (Glu). These three amino residues function as a nucleophile-base–acid catalytic system to facilitate esterification, and the

• Lewis acid-mediated semi-pinacol rearrangement, this work involved a CRL-catalyzed desymmetrization of prochiral diol 51 (prepared from aldehyde 50 in four steps), providing monoester 53 in 57% yield with 83% ee. Notably, 1-ethoxyvinyl 2-furoate (52) was selected as the acyl donor in this step to

• functional group manipulations, alcohol 103 was subjected to enzymatic oxidative kinetic resolution with the bacterium Gluconobacter oxydans, producing alcohol 104 and acid 105. The alcohol 104 with the desired C9 stereocenter was then converted into fragment 106 in nine steps, while acid 105 was recycled to

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• ][3]. Established sets of reactive probes are typically armed with electrophilic warheads that have the potential to target nucleophilic amino acid side chains. Most reactive probe sets bear cysteine-directed warheads [3][4][5][6][7], although sets have also been designed to target a wider range of

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• oxidation of amide and other amino acid side‐chain fragments. By tracking changes in this oxidation signal upon addition of an alkylating agent, we can infer whether the agent has effectively reacted with (and thus structurally altered) the protein. As illustrated by the black trace in the LSV plot, pure

• . When these agents alkylate the HSA amino acid residues (particularly reactive sites like lysine, cysteine, serine NH2, SH, OH-side chains, and possibly other nucleophilic groups), the resulting covalent modification can disrupt the electroactive centers responsible for the protein’s oxidation peaks

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• for different N-benzyl benzaldimines in moderate to good yields. In 1991, Shono’s research group described the electroreductive intramolecular coupling of aromatic diimines, carried out in DMF in the presence of methanesulfonic acid in a divided cell equipped with a lead cathode, a carbon rod anode

• reaction and a screening of reaction parameters such as solvents, electrodes materials, electrolytes, total charges, and concentrations of the reaction mixture was performed. All optimization studies were carried out using 0.5 mmol of 1a in the presence of methanesulfonic acid in an undivided cell (5 mL

• co-workers [44], the presence of a strong protic acid, such as methanesulfonic acid, MsOH, is essential to promote the intramolecular coupling. A control experiment revealed that when the electroreduction of 1a was performed in the absence of MsOH (Table 1, entry 3), no formation of the desired

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• the presence of a Lewis acid. The use of BF3·OEt2 gave a low yield of the desired alcohol 2 [29]. This was improved slightly with Sc(OTf)3 as the Lewis acid, which could be used substoichiometrically [30]. The alcohol 2 was converted to the tosylate 3 and subsequent ozonolysis gave the aldehyde 4. The

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

• with the more recently introduced inherent chirality. As one of the most prominent chiral organocatalysts, chiral phosphoric acid (CPA) catalysis has proven highly effective in synthesizing centrally and axially chiral molecules. However, its potential in the asymmetric construction of other types of

• within this domain. Keywords: asymmetric catalysis; chiral phosphoric acid; helical chirality; inherent chirality; planar chirality; Introduction Since the seminal works by Akiyama [1] and Terada [2] et al. in 2004 demonstrated the application of BINOL-derived chiral phosphoric acids (CPAs) in

• catalytic sites. The OH group on the phosphorus atom functions as a Brønsted acid site, while P=O serves as a Lewis base site, which enables the simultaneous activation of both nucleophiles and electrophiles in one reaction (Figure 1). The chiral properties of the catalysts are derived from the chiral

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• efficiency. Keywords: metal-organic frameworks; post-synthesis modification; supramolecular catalysis; Introduction Most enzymatic reactions take place in multifunctional cavities in which multiple amino acid residues work cooperatively to orient and activate reactants [1][2][3]. These residues may also

• enhance covalent and/or acid–base catalysis via any combination of non-covalent interactions (hydrogen bonding, π–π stacking, lipophilic interactions, etc) [4][5][6]. Inspired by enzymes, Nature's most efficient catalysts, chemists have long endeavored to synthesize catalytic materials in which multiple

• by increasing the binding affinity for the lipophilic reactants and by decreasing the energy required to desolvate acid/base amino acid catalysts [34][35]. Lipophilicity has also been found to be beneficial in condensation reactions as the removed water molecules are repelled by the hydrophobic

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• and subsequent reduction of 45 (if substrates 43 and 44 contain a NO2 group, this will also be reduced, Scheme 13A) [54], or by Wittig reaction and reduction of the isomeric mixture of alkenes 48 (Scheme 13B) [57]. Oxidation of 49 with oxone [58] or m-chloroperbenzoic acid [54] yields 35. Wittig

• methods for N-arylation depending on the aryl type: electron-rich and electron-neutral substituents are introduced via Chan–Lam coupling with an arylboronic acid, electron-poor aromatics via Cu(I)-catalysed cross-coupling with aryliodonium salts, and monosubstitution is achieved via Ullman–Goldberg

• aldehyde and, if required, N-functionalisation via nucleophilic substitution (for aliphatic substituents) or palladium-catalysed cross-coupling (for aromatic substituents) (Scheme 25) [77]. Hemithioindigo can be synthesised by treating phenylthioacetic acid (83) with triflic acid. Then, the product is

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• [53]. In this work, the authors used a stoichiometric amount of Zn(OTf)3 as a Lewis acid catalyst and air as the oxidant for the reaction. Jana and colleagues demonstrated an atom-efficient pseudo-three-component C–H annulation reaction catalyzed by Yb and Cu, which involved nitrosoarenes and styrene

• , the present C–H annulation reaction of aniline (1a) with styrene (2a) was initially carried out in TFE (trifluoroethanol) as solvent in the presence of 25 mol % FeCl3·6H2O as a catalyst and 1.5 equiv of TFA (trifluoroacetic acid) as an additive (Table 1, entry 1). For this reaction, 12% of 2,4

• cleavage as well as inadequate Lewis acid activation of N-methylaniline (1a′), which hinders its further cyclization into the final product 3a′. The reaction, when conducted in the absence of a catalyst, failed to proceed, thereby highlighting the crucial role of catalytic activation in facilitating the

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• 1–5e with para-methoxy group in the aromatic ring (Table 1, Supporting Information File 1, part 2). Typically thioformylium methylide is generated from compound I by action of CsF or TBAF [16][23][24]. We also tested other fluorides and trifluoroacetic acid (Supporting Information File 1, part 2

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• bisimidazolines are efficient chiral ligands in metal-catalyzed asymmetric organic transformations. Chiral cyclohexane-linked bisimidazolines were prepared from optically active cyclohexane-1,2-dicarboxylic acid and 1,2-diphenylethane-1,2-diamines via the monosulfonylation of 1,2-diphenylethane-1,2-diamines

• , condensation of N-sulfonylated 1,2-diphenylethane-1,2-diamines and cyclohexane-1,2-dicarboxylic acid, and the final cyclization with the in situ generated Hendrickson reagent. Keywords: bisimidazoline; cyclohexane; cyclohexane-1,2-dicarboxylic acid; 1,2-diphenylethane-1,2-diamine; Introduction Chiral

• bisimidazoline (PyBim) ligands derived from pyridine-2,6-dicarbonitrile or pyridine-2,6-dicarboxylic acid and vicinal diamines, as analogues of pyridine-linked bisoxazoline (PyBOX) ligands [16][17]. They exhibited excellent performance in metal-catalyzed asymmetric organic reactions. Chiral rigid backbone-linked

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• solubility, this can be improved through derivatization. Water-soluble calixarene derivatives can be obtained through functional modifications, including the introduction of sulfonic acid, amine, and carboxylic acid groups [57][58][59]. These water soluble macrocycle derivatives can be used to increase the

• a hot topic [75]. PAs can be prepared via the Friedel–Crafts condensation, which involves combining 1,4-dimethoxybenzene with paraformaldehyde in the presence of a Lewis acid. The central axis of these aromatic hydrocarbon molecules possesses n fold rotational symmetry [76]. PAs possess highly

• ]arene (WP7) by adding 14 anionic carboxylic acid groups to both sides [102]. They explored the pH-dependent complexation of WP7 with paraquat derivative G1 in water. The host WP7 and guest G1 form a 1:1 pseudorotaxane, with an association constant of (2.96 ± 0.31) × 105 M−1. Furthermore, they leveraged

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• oxidation in methanol in batch electrolysis conditions, providing unsaturated esters S-3d and R-3d, respectively (Scheme 2). The previously used one-reactor two-step conditions were found to be productive for the electrosynthesis of S-3d, requiring the addition of acetic acid for the intermediate spiroketal

• reaction, and we found that acetic acid served well for this purpose (Table 1, entry 4). Using the reaction conditions with acetic acid as additive, the reaction could be performed also in a 0.5 g scale for the synthesis of both ester enantiomers S-3d and R-3d (Table 1, entries 5 and 6). In the absence of

• acetic acid or HFIP the electrochemical oxidation also provided the desired product 3d, although in reduced yield (Table 1, entry 7). An increased amount of acetic acid (1 mL or ≈ 18 equiv) also reduced the yield (Table 1, entry 8). The attempt to use LiOAc as electrolyte instead of LiClO4 was not

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• receptor agonist and potential glucokinase activator, we developed a convenient synthetic route from commercially available indole-3-acetic acid. Treatment of the N-Boc-protected indole-3-acetic acid with N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide (EDC) in the presence of DMAP generates the N,N′-Boc

• ]. Herein, we report an alternative synthesis from commercially available indole acetic acid, and demonstrate that the approach can be extended to related compounds. Results and Discussion Previously, malassezione had either been (i) isolated from cultures of M. furfur grown on ʟ-tryptophan as the sole

• nitrogen source followed by thin-layer chromatography and reversed-phase (RP)-HPLC to isolate and purify the compound from a complex mixture of indole alkaloids [11], (ii) prepared by aerobic incubation of indole-3-pyruvic acid at pH 7.4, 37 °C for 24 h followed by isolation and purification using RP-HPLC

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• enantioselective molecular recognition. Different chiral backbones were used for the construction of such chiral crown ethers, especially chiral 1,2-diols such as tartaric acid [5][6][7][8], propane-1,2-diol [9][10][11][12][13], cyclohexane-1,2-diol [14], carbohydrates [15], 1,1'-binapthyl-2,2'-diol (BINOL) [16

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• the formation of a borate complex [61]. Diarylborinic acids have also been exploited for stereoselective 1,1'-glycosylations through the formation of a 1-O-monoborinate ester, resulting from the complexation of a 1,2-dihydroxyglycosyl acceptor with a diarylborinic acid derivative. Concurrent

• the orthogonally protected diol acceptor 36, proved to deliver optimal stereoselectivity and the highest yields in the reaction promoted by bistrifluoromethylated tricyclic borinic acid 40, affording β,α-1,1'-linked disaccharides 37 [63] and 39 [62], respectively, in 86% yield (Scheme 4). The nature

• of the 2N-protecting group on GlcN- and GalN-derived lactol acceptors proved crucial for the success of borinic acid-promoted glycosylation, as the 2N-Troc-protected acceptor 41 failed to participate in the reaction. In contrast, the 2N-naphthalenesulfonyl (NapSO₂)-protected glucosamine-derived

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• development, and (ii) refining existing synthetic processes through process intensification strategies. Nitric acid (HNO3) and its binary systems with sulfuric acid (HNO3/H2SO4) remain the industry-standard nitrating systems, particularly for the nitration of aromatic substrates. Motivated by environmental

• technologies including ultrasonication, microwave irradiation, and microreaction technology into conventional nitration frameworks. Nikseresht et al. developed a novel heterogeneous heteropoly acid catalyst (PMA@MIL-53(Fe)), enabled efficient regioselective nitration of phenols under ultrasonic irradiation

• , achieving 54.98% o- and 45.01% p-nitrophenol yields within 15 minutes [10]. Umrigar et al. demonstrated a microwave-assisted nitration of monochlorobenzene (MCB) for the efficient synthesis of 2,4-dinitrochlorobenzene (2,4-DNCB), achieving reduced reaction time, minimized waste acid, and enhanced yield

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• biomolecules in organisms. However, the R/S stereochemistry of pyruvate ketal is difficult to control through chemical methods. In this study, the acid-labile pyruvate ketal linked to the 4- and 6-positions of galactose was cautiously constructed, and the X-ray analysis of the R-configured product was

• the foundational work of Kulkarni, Codée, Boons, and other outstanding groups in their studies on zwitterionic polysaccharides [7][8][9][10][11][12]. Pyruvylation of carbohydrate diols is commonly achieved through acetal substitution in the presence of acid during chemical synthesis. In this process

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• hypophosphorous acid are commercially available in bulk amounts, however, their usage is understudied in organic processes. While NaH2PO2 has proved to be an efficient four-electron reductant in the catalyst-free reductive amination, the influence of cation in hypophosphite salt has not been studied yet. This

• the DFT calculations (Scheme 5, Figure 2). Firstly, reductive amination of an aldehyde started from a nucleophilic addition of the amine to the carbonyl group of the aldehyde. In the presence of acid, this step could occur via acidic catalysis involving a protonation step of an amine (Step_2) or

• absence of an external hydrogen source. The alternative pathway to form a hemiaminal could not include the interaction of an acid with amine or aldehyde, nevertheless, the non-catalytic path had ΔEa = 32.1 kcal/mol (TS2→3'') which meant that hemiaminal definitely emerged faster via the amine protonation

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• ] involving 6-aryl-2-aminopyridines 27, aldehydes, and isocyanides (Scheme 5a) [35]. By employing chiral phosphoric acid (CPA) C1 as the catalyst, this reaction worked well to afford axially chiral imidazo[1,2-a]pyridines 28 in high-to-excellent yields (up to 99%) and enantioselectivities (up to >99% ee). It

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• of a dehydroalanine derivative using silane-mediated halogen atom transfer [28]. Dual catalytic approaches that merge photocatalysis with Lewis acid [29], organo- [30], or transition metal catalysis [31] have enabled access to bond formations that are otherwise challenging to achieve. In particular

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• . Unfortunately, failure was encountered here. This can be expected because the reaction site here is a bridge quaternary center (no such example was reported in literature for this) [31][32][33]. Due to this, we then converted the ester group in 12 into a carboxylic acid group, reaching 13 in 72% yield. Finally

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• analysis in terms of stabilization energy. In addition, an analysis of the Anisotropy of the induced current density (ACID) plot [24] calculated for 1 (Figure 3B) shows a significant diatropic ring current formally associated with the peripheral model 1b. Another diatropic contribution can be assigned to

• Equation 1. (B) Anisotropy of the current induced density (ACID) diagram of compound 1. (isosurface value: 0.035 a.u.) (C) Bond distances (in Å) for fully optimized structure of 1, computed at the ground state (S0) and at the first singlet excited state (S1, in orange). Results obtained at the B3LYP-D3BJ/6

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• this perspective article, we shall show the relationship between transition-state aromaticity and reactivity in representative pericyclic reactions. Perspective Lewis acid-catalyzed Diels–Alder cycloadditions It is well-established that catalytic amounts of a Lewis acid (LA) can significantly

• following subchapter) but also to other processes such as aza-Michael additions or processes catalyzed by species able to establish noncovalent interactions with the reactants [52][53][54][55][56][57]. Lewis acid-catalyzed carbonyl–ene reactions Similar to the Diels–Alder cycloaddition reaction, the Alder

• , which is translated into high reaction temperatures that severely limit the scope of the process. Nevertheless, as Diels–Alder cycloadditions, Alder–ene reactions can be efficiently accelerated (i.e., having lower barriers) upon the addition of catalytic amounts of a Lewis acid [62], which again

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• -containing compounds [1][2][3]. Such reactions can be initiated by electrophilic, nucleophilic or radical reagents, photoirradiation or proceed under acid-, metal-, or photocatalytic conditions. This strategy of azirine ring expansion is applicable to the synthesis of a variety of 4‒9-membered N-heterocycles