Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• reaction of 87 was employed, generating both the kinetic product 88 and the desired thermodynamic product 89. Heating 88 promoted a retro-Diels–Alder/Diels–Alder equilibrium, favoring the more stable isomer 89. Palladium-catalyzed hydrogenation of the 1,2-disubstituted alkene in 89, followed by Mo(CO)6

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• that the cyclopalladation step is irreversible. To further investigate the nature of the C–H activation step, an intramolecular kinetic isotope effect (KIE) experiment was performed using monodeuterated substrate 1a-D1. A modest KIE value of kH/kD = 1.5 was observed under standard reaction conditions

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• catalytic performance. The developed catalytic system demonstrated high activity, excellent yields (mostly exceeding 85%), mild reaction conditions, broad functional group tolerance, as well as high regioselectivity, (E)-selectivity, and enantioselectivity (up to 99% ee). According to the kinetic study, the

Adaptive experimentation and optimization in organic chemistry

• Artur M. Schweidtmann and
• Philippe Schwaller

Beilstein J. Org. Chem. 2025, 21, 2367–2368, doi:10.3762/bjoc.21.180

• . provide a comprehensive review of machine learning applications in enantioselective organocatalysis, highlighting both achievements and remaining challenges [10]. Guo et al. present an automated flow chemistry system for nitration reactions, combining kinetic modeling with experimental optimization [11

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• pyridinium site. This light-driven shuttling was shown to be fatigue-resistant over multiple cycles, highlighting the robustness of the system. Notably, the authors also reported a general quantification of kinetic asymmetry in a multicycle chemical reaction network, establishing a framework applicable to

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• (20 mg) is used. Kinetic studies conducted for both hosts H2 and G2W1 in the removal of methylene blue and methylene violet, respectively, demonstrate a rapid sequestration process that reaches a plateau within 30 minutes. In conclusion, this study highlights the importance of avoiding host structural

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• oxymethylene bridge in the 2D NOESY NMR spectrum. Given the instability of fluoro-ketone 13, a one-pot procedure was developed in which the reaction mixture containing 13 was subjected to the Baeyer–Villiger oxidation with H2O2 giving the fluorinated and stable lactone 14, which is the expected kinetic product

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• regulatory role in chemical transformations, exerting kinetic modulation through solvation effects on activation barriers and reaction rates, dictating thermodynamic equilibria that govern product distribution, and enabling precise reaction pathway regulation via selective stabilization of critical

• control principles for gold catalysis. Temperature-controlled cyclization of 1,n-enynes Temperature, a pivotal thermodynamic parameter, not only governs reaction kinetics but also determines reaction pathways. Typically, kinetic product formation is favored at lower temperatures via pathways with reduced

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• physicochemical and early ADME characterization study, in the framework of which logP, pKa and logk values were calculated. Following that, kinetic solubility and in vitro gastrointestinal membrane-specific permeability measurements were carried out to assess the lead-likeness of the compounds. Subsequently, the

• results of physicochemical and early ADME characterization for hydrazones 7 and 9, and target compounds 3 and 10 are summarized in Table 2 and Table 3, respectively (individual column charts on kinetic solubility, permeability, and membrane retention measurements can be found in Supporting Information

• surface area (TPSA) values fell in a desirable range (40–90 Å2) (see the extended table on physicochemical parameters in Supporting Information File 1, Table S1). Based on their pKa values, all compounds are non-ionizable or slightly basic. Kinetic solubility was considered good above 30 µM, moderate

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• 50% yield and 99% ee after kinetic resolution using Escherichia coli (Scheme 57) [189]. Other reactions: Yamamoto synthesized 6-hydroxy-2-(trifluoromethyl)-2H-pyran-3(6H)-ones from furfural via trifluoromethylation using the Ruppert–Prakash reagent (TMSCF3), followed by a photo-Achmatowicz reaction

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• similar compounds based on 5-amino-1H-pyrazole-4-carbonitrile [22]. It should be noted that diazocines 4 were stable and did not undergo transformations when heated or irradiated with ultrasound. This may indicate that pyrimidine-7-carboxylic acids 5 and 6 are formed in parallel processes under kinetic

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• to experimentally measure the stereoselectivity of the reaction. In 1965, Crawford and co-workers experimentally found kinetic evidence for a 1,3-diradical from the thermal decomposition of 1 [56]. In 1963, Steel investigated the photolysis of diazabicyclo[2.1.1]hep-2-ene in solution, and the

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

• suppress potential intramolecular acyl migration. To further improve the optical purity of monoester 53, a Pseudomonas aeruginosa lipase-mediated kinetic resolution was performed with ethoxyvinyl butyrate 54, ultimately achieving monoester 53 with 97% ee in 60% yield and the diester 53a. With

• -worker described the asymmetric synthesis of (−)-rasfonin, harnessing an enantioselective enzymatic desymmetrization with lipase AK and an enzymatic oxidative kinetic resolution to install stereocenters [47]. The synthesis commenced with the preparation of fragment 100 from ethylene glycol (97) (Scheme

• 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

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

• without the CPA catalyst. Notably, indolohelicenoid 23e could effectively be converted into the fully aromatic indolohelicene 24e under DDQ-mediated oxidative conditions without compromising the enantiopurity of the compound. Kinetic resolution stands as one of the most practical and efficient strategies

• ]. While CPAs have been extensively utilized in kinetic resolution of centrally chiral [26][27][28] and axially chiral compounds [29], their application in the kinetic resolution of helically chiral compounds remains largely unexplored. In 2024, Liu and co-workers developed an effective method for

• catalytic kinetic resolution of racemic helical polycyclic phenols through an organocatalyzed enantioselective dearomative amination reaction [30]. The racemic polycyclic phenol derivatives 25, which exist as single diastereomers featuring both central chirality and helical chirality, were readily prepared

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

• absence of light. Apart from some special cases where more competing mechanisms are operating [5], the thermal isomerisation typically is a first-order decay: Where I is the monitored signal at the time t, I0 the initial signal, and k the kinetic constant. Once k is known, the thermal half-life t1/2 can

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

• processes. For example, supramolecular self-assembly technology enhances the targeting of chemotherapeutic drugs to tumor tissues, reducing systemic adverse reactions. (3) Macrocyclic aromatic supramolecular nano-valves have a pseudo-rotaxane structure with host–guest coordination and the kinetic properties

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

• '-neotrehalosamines 7 and 9, respectively (Scheme 1) [38]. The stereochemical outcome was found to be independent of the initial anomeric configuration of the N-phthalimido-protected lactol acceptor, which was explained by kinetic control and a rapid anomerization in favor of the β-anomer [50]. The applicability of

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

• classifications necessitate tailored nitrating reagent selections, giving rise to fundamentally distinct mechanistic pathways. This reactivity is exemplified by the comparative kinetic profiles: N-nitration of amines and O-nitration of alcohols – facilitated by accessible lone electron pairs – exhibit markedly

• higher kinetic feasibility than aliphatic C-nitration in saturated carbon frameworks [3]. Following determination of substrate–nitrating agent combinations, reactor system specification emerges as the critical engineering decision. Nitration reactor selection – encompassing batch, semi-batch, continuous

• , throughput, and side reactions. The reaction temperature (usually 0–60 °C) governs kinetic rates and selectivity, where lower temperatures suppress polynitration reactions while higher temperatures demand enhanced heat dissipation. The molar ratio of HNO3/substrate (usually 1.0–3.0) directly regulates the

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

• the target amine (Scheme 4c). The experiments with H3PO2 and D3PO2 resulted in the same yield of the amine obtained from enamine under the same reaction conditions. Thus, the kinetic isotope effect (KIE) was not observed in reduction of enamine. Although the experiments with D3PO2 did not allow us to

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

• unsymmetrical diisocyanide was used, the initial isocyanide insertion was found to be non-regioselective, delivering a 1:1 mixture of regioisomers (17c and 17c’). Intriguingly, 17a could act as a chiral acylating reagent, applying in the kinetic resolution of racemic primary amines rac-18. Additionally, after

• reaction between alkene 43 and 2,2′-dienone 44. The corresponding spirooxindole 45 was obtained in >19:1 dr, 63% yield, and 89% ee. Dynamic kinetic resolution of configurationally labile bridged biaryls The catalytic asymmetric dynamic kinetic resolution (DKR) of configurationally labile bridged biaryls

• Groebke–Blackburn–Bienaymé reaction. Construction of axially chiral 3-arylpyrroles via de novo pyrrole formation. Synthesis of atropoisomeric 3-arylpyrroles via central-to-axial chirality transfer. Dynamic kinetic resolution of bridged biaryls with α-acidic isocyanides. Desymmetrization of prochiral

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• to resolve into the evolution-associated spectra (EAS) [19]. The spectral evolution over time was tentatively analyzed using a three- or four-component sequential decay model (for example, the four-state kinetic model is described as EAS1 → EAS2 → EAS3 → EAS4 → ground state). Figure 6a and 6c show

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• 3–7, with different electron-donating or electron-withdrawing substituents at the para-position of the phenyl ring conjugated with the amidine moiety. The same kinetic analysis was performed for compounds 3–7 at pH 4.0, 4.5, 5.0, and 5.5, and the results are summarized in Table 1. In addition, the

• peaks corresponding to the atropisomers arising from the C–C axis. Each atropisomer could be separated by chiral HPLC, and the isomer eluting earlier was used for the following kinetic analysis. The effect of pH on the kinetics of the racemization was investigated. The isomer was heated in the buffer

• protonated form calculated by the DFT method. Comparison of VT-NMR spectra of a) amidine 1 and b) its trifluoroacetate salt 1-H+ in DMSO-d6 (400 MHz). Separation and isolation of amidine E/Z isomers by RP-HPLC. The mobile phase contained CF3CO2H to protonate the amidine moiety. Kinetic analysis of the

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

• challenging amines. The combination of simple reaction conditions and excellent chemoselectivity makes this protocol very robust and suitable for both the academia and industry. Kinetic and computational experiments support an SN1 mechanism via loss of sulphur dioxide and oxetane carbocation formation. Two

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• mechanism, control experiments were conducted. The addition of radical scavengers such as BHT and TEMPO significantly inhibited the reaction, confirming the involvement of a radical intermediate. Kinetic isotope effect (KIE) studies showed a KIE of 1.0, suggesting that C–H-bond cleavage was not the rate

• instability of the intermediate radicals. Control experiments were conducted to elucidate the reaction mechanism. A kinetic isotope effect (KIE) experiment demonstrated that C–H bond cleavage in DCM was the rate-determining step. Further investigations confirmed that the reaction relies on the generation of

Optimized synthesis of aroyl-S,N-ketene acetals by omission of solubilizing alcohol cosolvents

• Julius Krenzer and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2025, 21, 1201–1206, doi:10.3762/bjoc.21.97

• from in the process. For suppressing the formation of side products by self-condensation of S,N-ketene acetal intermediates the reaction temperature has to be kept as low as possible for assuring kinetic control. Therefore, in contrast to the standard protocol [5][6] (Scheme 2), reacting aroyl

• , kinetic control is warranted by conducting the condensation synthesis at room temperature for only short reaction times. Furthermore, 2-MeTHF was successfully implemented as a sustainable alternative to 1,4-dioxane. This modified protocol is clearly superior to the initial protocol (in 1,4-dioxane/ethanol