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

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• meaningful correlation between thermodynamic stability and kinetic accessibility, as expressed by the BEP principle. Although this principle has been successfully applied in many cases, the correlation between reaction energies and activation barriers is often imperfect. For instance, studies on hydrogen

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

• allyl ester (R)-120 via enzymatic kinetic resolution of readily available rac-118 using Novozyme 435 and vinyl acetate in pentane at 30 °C (Scheme 19). The reaction was halted at the conversion of 54%, yielding the remaining alcohol (S)-118 with >99% ee. The product (R)-119 was subsequently treated with

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• -position of the pyrazine ring [10][11]. During small-scale late-stage functionalisation of natural products, we have observed that amination or amidation with primary amines often involves less of a kinetic barrier than might otherwise be expected [12][13][14]. The use of readily available liquid amines in

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• (Scheme 21C) [55]. Kawabata and co-workers (2020) prepared the β-glycoside 66 from α-ᴅ-glucose and cinnamic acid (7) in good yield through the Mitsunobu reaction (Scheme 22) [56]. The 13C kinetic isotope effect experiment (KIE = 1.028) showed that the glycosylation proceeded via SN2 substitution (67). Sun

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• , Hangzhou 310018, Zhejiang, China 10.3762/bjoc.21.75 Abstract A convergent approach for the enantioselective construction of an advanced intermediate containing the [5,5,6,6]-tetracyclic core framework of the khayanolide-type limonoids was described. The strategy features an acylative kinetic resolution of

• promoted by LiHMDS gave alcohol 17 with high regioselectivity (14:1 dr at C17) after an extensive screening of bases (LDA, NaHMDS, KHMDS, etc.). Drawing inspiration from the pioneering work of Birman [38], as well as Newhouse’s applications [18][19], an acylative kinetic resolution of the alcohol was

• ]). Conclusion In conclusion, we have developed a convergent approach for the enantioselective assembly of an advanced intermediate en route to krishnolides A and C. Key steps of our strategy entail an acylative kinetic resolution of the alcohol, a 1,2-Grignard addition and an AcOH-interrupted Nazarov

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• reduction with LiAlH₄, which led to a further decrease in the degree of unsaturation of the pyrazolodiazepine core, while the more sterically hindered exocyclic amide moiety remained intact. However, both reactions were accompanied by partial epimerization, and careful kinetic control was therefore required

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

• enantioselective access to both enantiomers of chiral P(V) molecules 47 or 48 using a single chiral NBE catalyst. Time control Time control of chemical reactivity offers an inherent strategy to program synthetic pathways through kinetic discrimination of transient intermediates. Diverging from additive-dependent

• 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

• six-membered nickel ring captures radicals and undergoes reductive elimination to form β-products (kinetic control); at high temperatures, the formation of a five-membered nickel ring leads to α-products (thermodynamic control). Therefore, the formation of the more stable nickel ring drives migration

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• observations made during prolonged irradiation experiments. Due to the thermal instability of O-QC2 noted during the investigation, kinetic experiments for determining the half-life time t1/2 were not conducted. However, the addition of CoII-porphyrin POR allowed for the successful regeneration of the parent O

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

• kcal·mol−1 higher in energy, resulting in a theoretical ee value of 74% (at 263 K), if pure Z-hydrazone would be used and under the assumption of kinetic reaction control. In contrast, the E-hydrazone gives preferably the "R" product (with a theoretical ee value of 64%). The transition state which gives

• of the relative stabilities of different forms of this complex. Consequently, under kinetic reaction control, enantioselectivity would decrease over time as the reaction progresses. This occurs because slower-reacting complexes would accumulate, leading to a gradual equilibration of reaction rates

• energy than that of the entry channel (1 + 7 + 8, Figure 3). Because the rate-determining and configuration-determining steps are different, reaction control of the whole multistep transformation in terms of enantioselectivity is therefore neither predominantly thermodynamic nor predominantly kinetic

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• thermodynamically stable EE isomer was followed over time starting from the PSS@365 nm. The kinetic traces of the relaxation process were recorded by 1H NMR spectroscopy at 37 °C (Supporting Information File 1, Figure S2) and the population of the EE, ZE, EZ, and ZZ isomers were plotted against time. Using a

• published tailor-made fitting program [24], the rate constants k1–k4 were extracted from the kinetic traces and are summarized in Table 2. The thermal relaxation of the glycoazobenzene antennas 3, 4, and 5, on the other hand, was monitored by UV–vis spectroscopy at 37 °C and the rate constants k5, k6, and

• from ZZ to ZE is practically not observed because it is so slow (for kinetic traces cf. Supporting Information File 1, Figure S2). Furthermore, the data reveal that the isolated glycoazobenzene antennas 3, 4, and 5 relax faster than the AB and ABF4 moieties comprised in the homobivalent glycocluster 2

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• otherwise predominant β-F elimination from the α-CF3-alkylcopper intermediate 39. Detailed kinetic studies confirmed the effect of the crown ether. When KOPiv was employed alone, the initial rate of defluorination increased by 1.57-fold, whereas the addition of 18-crown-6 reduced this acceleration to 1.22

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

• , Universidad de Valladolid, Paseo Belén 7, 47011-Valladolid, Spain 10.3762/bjoc.21.34 Abstract The pharmaceutical chemical industry has long used kinetic resolution to obtain high-value compounds. Organocatalysis has recently been added to this strategy, allowing for the resolution of racemic mixtures with

• low catalyst loadings and mild reaction conditions. This research focuses on the kinetic resolution of 1,5-dicarbonyl compounds using a retro-Michael reaction, co-catalyzed at room temperature with 20 mol % of the Jørgensen–Hayashi catalyst and PNBA. The study highlights the importance of conducting

• the kinetic resolution at a concentration of approximately ten millimolar (mM) to prevent the Michael retro-Michael equilibrium from affecting the process. Keywords: 1,5-dicarbonyl; equilibrium; kinetic resolution; organocatalysis; retro-Michael; Introduction For many years, enantiomers have been

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

• a coordinated mechanism. Noteworthy, the primary kinetic product of the cycloaddition reaction 5 is not transformed into the thermodynamic product 6 via a H-shift at the last stage. The expected aromatization with the formation of a furan ring, as happens in similar reactions, does not occur (Scheme

• ,5,6,7,7a-hexahydro-3aH-furo[2,3-f]isoindoles via Ugi/IMDAV tandem reaction. Kinetic product 5 does not transform into thermodynamic product 6. Synthesis of compounds 6a. Synthesis of compound 7. Synthesis of compounds 9. Supporting Information Supporting Information File 4: Experimental procedures

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• self-directing and self-correcting, and the term “self-assembly” [290][291][292] often used [286][293][294][295][296]. Products can be thermodynamic or kinetic, but are often isolated by precipitation due to low solubility [297], though many have useful solubility [288][298]. Since POCs typically have

• ], which in many cases is the only way to understand pure substituent effects (e.g., on catalysis). To enable the validation of this process, experimentalists must collect data relevant to benchmarking computations: binding constants, kinetic barriers, crystal structures. In turn, this process will be

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

• ignored [26][27][28]. However, recent experimental, kinetic, and physical data reveal the incidence of more associative mechanisms [29][30][31] wherein the mechanistic pathway of glycosylation seems to lie at an interface of SN1–SN2 reaction (Scheme 1) [29]. The continuum mechanism expands in two

• pathway through an associative transition state to form the equatorial glycoside, 7. Surprisingly, recent evidences show that typical homogeneous glycosylation reactions in organic solution shift more towards the SN2 end of the mechanistic spectrum [32][33][34], with some exceptions [35]. The kinetic

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• ] reported a stable heptacene dication in concentrated sulfuric acid, a stability attributed to the intermolecular Coulomb repulsion between the charged molecules, which prevents the dimerization of the acene. This exciting finding suggests possible modes of kinetic stabilization of oxidized species of π

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• family of photochromic compounds. This study explores the photochromic properties and thermal back reactivities of various aza-diarylethene regioisomers (N1–N4 and I1–I4) in n-hexane. These molecules exhibit fast thermally reversible photochromic reactions driven by 6π aza-electrocyclization. Kinetic

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

• substrate scope of boronic acids was limited in this transformation. To elucidate the reaction process, kinetic and control experiments were conducted, which led to the proposed reaction pathway for the copper-mediated synthesis of N-arylamides from dioxazolones as shown in Figure 4. Initially, copper(I

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

• enantioselectivity. First, the reaction of ketimine ester 33 and 2,3-dimethylhydroquinone at 10 °C provided the chiral 1,4-addition product 35 via dynamic kinetic asymmetric transformation (DyKAT). Conversely, when the reaction was performed at −10 °C, the reaction pathway switched from DyKAT to kinetic resolution

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

• enantioselectivities in similar desymmetrization reactions [39][40][41][42]. The dynamic kinetic resolution (DKR) of racemic 2-arylbenzaldehydes 62 with α-bromoenals 63 led to axially chiral products 64 [43]. Triazolium salt C20 as an NHC pre-catalyst was the most efficient for achieving high yields and enantiomeric

• enantioselectivities. Compound 66d was incorporated into a thiourea organocatalyst framework and successfully tested in kinetic resolution with 73% enantioselectivity. The chiral phosphoric acid (CPA) (R)-C22 was used to catalyze the formation of a C–N chiral axis in the axially chiral product 68 from biarylamines 67

• enantioselectivity during the nucleophilic addition, and the subsequent aromatization completes central-to-axial chirality conversion delivering products 68. Dynamic kinetic resolution of naphthylindoles 69 was performed by reaction with bulky electrophiles such as azodicarboxylates 70 or o-hydroxybenzyl alcohols 72