A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• efficient method for C–H functionalization. The continuous flow setup allows for precise control over reaction conditions, enhanced mass transfer, and improved reaction kinetics, leading to higher efficiency and faster reaction times. In 2023, the Chiang group reported the photoelectrochemical homo-coupling

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• for highly viscous reaction systems, especially at higher reactant concentrations. It is still difficult to eliminate the mass transfer effect using conventional microreactors, leading to errors in the determination of nitration kinetics. Therefore, more efficient mixers are needed to overcome the

• -order (Equation 3) reaction kinetics, where xIO represented the conversion of IO and t denoted the reaction time. The outcome of these fittings is presented in Figure 3a for first-order and Figure 3b for second-order. Notably, the higher R2 observed in Figure 3a compared to Figure 3b suggests that the

• reaction of IO follows first-order kinetics. Given that the reaction order of IO was determined to be 1, Equation 1 was subsequently transformed into Equation 4. As nitration reactions are predominantly second-order, we explored the potential for the reaction order of HNO3 (β) to be either 0 or 1 by

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• significantly slower activation, which results in an amide consumption of only ca. 30% after 4 hours. To quantify the activity differences of these XB donors, the reaction kinetics were fitted according to a pseudo-first-order rate. Only selected periods (the first four data points within the first 1.5 hours of

• kinetics of the gold-catalyzed cyclization shown in Scheme 2. An equimolar amount of the gold complex was applied, respectively. Every experiment was performed three times (see Supporting Information File 1). Synthesis of the iodoloisoxazolium salts 7Z: (a) 1.5 equiv 9, 0.2 equiv CuI, 2.0 equiv K2CO3, (THF

• TOFs of the strongest activators 2BArF, 7BArF, and 4BArF (and their calculated standard deviation). The TOFs were determined from the kinetics (see Supporting Information File 1 for further details). Supporting Information Supporting Information File 107: Synthesis, catalyses, and characterization

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• (IEDDA), and recently, azomethine imine (AMIs)–isonitrile ligation [37][55][56][57][58][59][60]. The kinetics, chemoselectivity, stability, and steric demand of the bioorthogonal tag attached on the probe are decisive factors during the selection procedure [61][62]. The most commonly used strategy is

• CuAAC due to its rapid reaction kinetics, robustness, and relatively small steric hindrance of the terminal alkyne, which is usually attached to the probe core scaffold to form an alkyne probe [5][63]. Once the covalent bond between the probe and protein is formed, the cells are lysed, and the probe

• thus introduces a searchable moiety and therefore clearly tags the MS/MS spectra derived from probe–peptide conjugates [113]. Another DADPS-based linker improves the CuAAC kinetics by using picolyl azide [115]. Together, the application of the acid-cleavable DADPS linkers is a feasible alternative to

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

• , signaling the binding of HFIP to 2c enhanced the electron transfer kinetics between the hypervalent iodine reagent and the electrode [45]. Further additions of HFIP further increased the current response and shifted the peak potential, with 10 µL and 15 µL of HFIP showing responses with Epr at −1.55 V and

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

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• indicates that the formed double azide adduct is 6a, which is consistent with our previous report [18]. The double azide addition was further investigated by changing the reaction temperature. The rate constant was determined by the temperature-dependent 1H NMR spectra in CDCl3. The reaction kinetics

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• and changes in the reaction kinetics. The non-covalent immobilisation of chiral organocatalysts can also be carried out within deep eutectic solvents (DESs). Very recently, a cinchonidine-squaramide organocatalyst was immobilised in three types of natural DESs, namely betaine/sorbitol/water, betaine

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• –ligand complexes, and analyse MD outcomes. Moreover, selected case studies have been reported to highlight the importance of computational tools in studying protein–glycan systems, revealing the capability of these tools to provide valuable insights into the binding kinetics, energetics, and structural

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• brilliance of synchrotron X-ray sources enables the mechanisms of structural changes in PS to be studied, using in-situ light irradiation with time-resolved data collection. For example, Tribet and co-workers used this approach to explore the kinetics of micellisation and dissolution of cationic Azo-PS, both

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• measurement altering the kinetics of isomerization, a known problem for similar setups [24]. The power readings from the thermal power sensor were recorded by using Thorlabs’ Optical Power Monitor (OPM) software. The resulting data showed some fluctuations depending on environment temperature and air movement

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

• and oxidation potentials. Electrochemical methods Synthetic electrochemistry is a powerful tool offering excellent control over reaction kinetics and selectivity [86]. Electrochemical oxidation has been demonstrated as an efficient means for generating benzylic cations, allowing for the introduction

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• investigations into the kinetics and stereochemistry of hydrochlorination reactions. However, both aspects are highly dependent on the reaction conditions and substrates, and no general conclusions could be drawn [3][4][5][6][7][8][9]. Research activity in this field remained relatively dormant until the early

• dependence. Brown also explored the influence of solvents (Figure 4). While reactions conducted in neat α-methylstyrene (11) or dichloromethane showed identical kinetics, the reaction was delayed when pentane was employed as a solvent. The method of bubbling HCl gas through neat alkenes or solutions of

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• approaches have diligently explored the details of reaction kinetics, quantitatively elucidating the impact of encapsulated Li+ on the reactivity of the outer fullerene cage as a specialized “encapsulated” Lewis acid catalyst [10][11]. While previous studies have revealed valuable insights, such as

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• different substrates when compared to known myo-inositol dehydrogenases and has a more similar substrate scope to scyllo-inositol dehydrogenases. We performed kinetics analysis for Hyg17 with myo- and scyllo-inositol (Table 1 and Figure 2d,e). The KM value for Hyg17 with myo-inositol was 9.0 ± 1.1 mM, which

• containing 3.7 mL p-anisaldehyde, 135 mL ethanol, 5 mL sulfuric acid, and 1.5 mL glacial acetic acid. Light pink spots were observed following heating at 105 °C. Kinetics assays were carried out by varying concentrations of substrate (myo-inositol or scyllo-inositol) from 1 mM to 60 mM with 1 μM Hyg17 and 10

• mM NAD+ in 100 mM CAPS, 50 mM NaCl, pH 10.5. Additional kinetics assays were carried out by varying concentrations of NAD+ from 1 mM to 40 mM with 1 μM Hyg17 and 10 mM myo-inositol in 100 mM CAPS, 50 mM NaCl, pH 10.5. The production of NADH was monitored and initial reaction rates calculated by

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• that no new atoms are introduced into the molecule, thus ensuring first-order kinetics of the process without complexity. One of the possible mechanisms of redox-induced switching involves an intramolecular bond formation that introduces non-covalent interactions between tweezers endpoints leading to a

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• , Table 2, entry 4). We were not able to determine the maximum impact of added MeOH, because the rate of cyclization became too fast to be detectable by 1H NMR kinetics (t < 5 minutes). A LN-LN plot of MeOH concentration versus observed rate gives a slope of 0.7, indicating less than first order

• molecule of amine delivers a proton to the alkylgold intermediate (for protodeauration). In a platinum-catalyzed hydroamination, a protodemetalation pathway is supported by kinetics and reactivity studies on generated platinum alkyl intermediates [46]. In a palladium-catalyzed hydroamination, a

• protodemetalation pathway is also supported by kinetics and reactivity studies on generated palladium alkyl intermediates [47]. Formation of alkylgold intermediates is known to proceed with anti-attack [27] and the stereospecificity observed in deuterium-labeled intermediates was used as an argument for

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• ) spectroscopy to derive binding constants for the interaction between CMA1 and GalNAc. A single cycle kinetics approach was applied, resulting in a measured KD of 1.66 ± 0.08 µM (Figure 3d,e). Inhibiting binding of CMA1 to the GalNAc chip through a dilution series of N-acetyllactosamine (LacNAc) via multicycle

• kinetics allowed us to derive an IC50 of 1.4 µM (Figure S2a,b; Supporting Information File 2). No inhibition was observed with chondroitin 6-sulfate tetrasaccharide (CSC), and only very weak inhibition for BGHT2 but no IC50 could be determined as we could not increase the concentration to reach the plateau

• produced CMA1 with GlcNAc, GalNAc, and H type 2 blood group antigen (BGHT2; Fucα1-2Galβ1-4GlcNAcβ1-3Gal) and measured a denaturation curve to assess shifts in melting temperature, n = 3 (c). (d, e) SPR analysis of CMA1 binding to a GalNAc chip with single-cycle kinetics and affinity measurement at the

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• using a high-pressure mercury lamp equipped with a sharp cut filter (λ > 380 nm), which resulted in a smooth conversion into the PBI product 6a within 20 min. Interestingly, the sulfoxide derivative exhibited enhanced kinetics, as confirmed by UV–vis spectroscopy and NMR experiments. The latter was also

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• Corporation [79], in which the inventors succeeded in the synthesis of water-soluble indigo derivatives and applied these compounds as solar energy storage systems using the aforementioned energy storage mechanism. However, detailed studies on kinetics and thermodynamics of the photoisomerization and thermal

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• acceptors like 2b, which have acyl groups protecting the C6 position, the reaction kinetics become sluggish, resulting in low conversion rates or no conversion [36][39]. Results and Discussion In our studies, the initial glycosyl donors and acceptors (Figure 2; compounds 1a–g and 2a,b) were synthesized

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• -order kinetics, indicating a bimolecular process. Furthermore, their findings elucidated a compelling linear free-energy relationship between the rate constants and electronic characteristics of the para-substituents of the DCV electrophiles, implying a dipolar, zwitterionic mechanism. The researchers

• through the reaction of 1 with 1,1-dicyanoethene (14). They demonstrated that this intermediate was converted into the corresponding TCBD 15 upon further heating, as depicted in Scheme 7. The kinetics of the RE step conformed well to that of a first-order reaction. However, notably, they underscored that

• 1H nuclear magnetic resonance (NMR) spectroscopy. Their investigation revealed that the product plays a pivotal role as an autocatalyst in the kinetics, as illustrated in Scheme 8 [104][105][106]. The traditional model posits that an alkyne (A) and TCNE (designated as B in Scheme 8) initially form a

Optimizing reaction conditions for the light-driven hydrogen evolution in a loop photoreactor

• Pengcheng Li,
• Daniel Kowalczyk,
• Johannes Liessem,
• Mohamed M. Elnagar,
• Dariusz Mitoraj,
• Radim Beranek and
• Dirk Ziegenbalg

Beilstein J. Org. Chem. 2024, 20, 74–91, doi:10.3762/bjoc.20.9

• the hydrogen evolution, which enabled sampling every 3 minutes and thus provides insights on the kinetics of hydrogen evolution. Compared to conventional manual sampling with gas-tight syringes, online measurements also improve reproducibility by minimizing potential errors such as contamination by

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• and exhibit a negative solvatochromism. An analysis of the kinetics of the zwitterion formation was performed for three Michael acceptors (acrylonitrile, methyl acrylate, and acrylamide) in two different solvents (chloroform and methanol). The results revealed the proton transfer step necessary to

• step the kinetics of the formation of the Michael adducts were studied. For this purpose, we used two strong and one weak Michael acceptors, which were selected according to their electrophilicity parameters (E) [39][46], their performance in previous testing [14] and the nature of the functional group

• the concentration of the phosphine 1 ([1] = 0.25 mmol/L) to obtain pseudo first-order kinetics. Figure 4 shows typical time vs conversion plots for an initial Michael acceptor concentration of 7.5 mmol/L. Time conversion plots were then evaluated using COPASI [47]. To obtain second-order rate

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• ) within 1 h. This property is probably due to the high stability of CmaA6. The high activity of CmaA6 makes it a useful tool for biochemical experiments and chemoenzymatic synthesis. Indeed, the discovery of CmaA6 allowed us to analyze the kinetics of the denitrification reaction catalyzed by AvaA7, which

• -coumaric acid via diazotization-dependent deamination. The diazotase CmaA6 had a high catalytic activity, which enabled us to determine the kinetics of the denitrification reaction catalyzed by AvaA7. Furthermore, careful comparison between ava and cma clusters provided insights into (i) the mechanism of