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

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

• , indicating that the activated gold complex is the catalytically active species. Furthermore, stability measurements (1H and 19F NMR) of 1:1 mixtures of the gold complex and the XB donors were performed in order to investigate the stability of the cationic iodonium structures towards the gold complex [28

• ]. For all catalyst systems, decomposition of the −BArF24 anion was observed via 1H and 19F NMR spectroscopy, which is known to happen in the presence of activated gold complexes [29]. The stability of the DAI cations was checked with 1H NMR: the characteristic doublets belonging to the respective

• iodonium structures 1+, 2+, 3+, and 7+ were found to be constant (see Supporting Information File 1). The signals of the iodoxinium cation 4+ were overlapping with signals of the anion. However, the stability of 4+ (as well as of 2+) could be confirmed by 19F NMR measurements: no decomposition of the

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• recorded for compound 1f – 36.9%. Therefore, the synthesized triazinones 1 exhibit a wide range of NO-releasing properties and could be considered as potential drug candidates. Additionally, thermal stability of the obtained triazinones 1 and 7 was evaluated by differential scanning calorimetry. The

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

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• stability of thioester groups in aqueous environments, we also decided to apply conditions conducive to hydrophobic amplification [37], which unfortunately also did not yield the intended effect. Another approach is to generate and stabilize the active nucleophile form as an anion thus increasing its

• guanidine motif in AA-3 compared to simple AA-1. Alterations in the thiol structure within thiomalonates significantly impact their stability and reactivity, thereby influencing both reaction efficiency and stereochemical outcome, as demonstrated in the case of catalysis employing bifunctional hydrogen bond

• for phenyl bis-thiomalonate 3. The reaction in toluene required 24 hours to yield an enantiomerically enriched product (92% ee) with a 69% yield. However, achieving such a degree of over-reaction was associated with prolonged reaction times, which may affect the stability of both the substrate and its

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

• with the stability of the relevant iminoiodinane reagent, with higher yields attributed to more electron-rich sulfonamide substitution such as 2a. Relatively electron-deficient iminoiodinanes are less efficient but are also more prone to decomposition (see Supporting Information File 1, Figure S2 for

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

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• analyses of microsomal stability confirm prolongation of t1/2 of the new deuterated analogs. We also report the first preparation of [D2]-isonitriles from [D3]-formamides via a modified Leuckart–Wallach reaction and their use in an MCR to afford products with [D2]-benzylic positions and likely

• significantly enhanced metabolic stability, a key parameter for property-based design efforts. Keywords: deuterated aldehydes; deuterated formamides; deuterated isocyanides; DHPs; kinetic isotope effect; Leuckart–Wallach; microsomal stability; multicomponent reactions; Introduction Multicomponent reactions

• [D3]-formamide. The ability to deuterate at benzylic positions is particularly relevant as benzylic C–H bonds are common in biologically relevant chemotypes and moreover appear in approximately 25% of the top selling 200 pharmaceuticals [23]. Benzyl cation stability is a driver of metabolism at these

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• . Previously, we reported aromatic hydrocarbon radicals with 9-anthryl (Ant) units at the spin-center carbon, exhibiting high stability (Figure 1a) [16][17][18][19][20][21]. Although bulky phenyl substitutions at the spin-center carbon can also provide high stability [13][14][15], the introduction of an Ant

• state yields the monomer radical [16][17][18]. Therefore, aromatic hydrocarbon radicals with Ant units possess both stability and reactivity depending on the conditions, giving them high potential for use as reactive catalysts [22][23] and stimuli-responsive sensors [24][25]. To further investigate this

• from the basic skeleton of the highly reactive diphenylmethyl radical [26][27][28]. This spin delocalization is similar to that of the galvinoxyl radical, which shows high stability in air [29]. Thus, the DAntM radical would be a stable radical with a reactive site. Additionally, utilizing the reactive

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• alcohols, polyols, polyions or polymers, has a positive effect on protein stability and the soluble fraction expressed with CFPS [17]. The variable composition of CFPS systems with a high number of ingredients and possible reaction conditions [13] thus opens a large parameter space. In addition, non

• the impact of the polymer itself is greater than that of the increased viscosity. A positive effect on the stability and activity of the model enzyme β-ᴅ-glucuronidase by the addition of carboxymethylcellulose has already been reported [49]. However, the effects and states of molecular crowding in the

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

• ), which are readily accessible by the oxidative acetylenic coupling of a 1,2-diethynylbenzene derivative (Figure 1) [18]. The chemical stability of DBAs depends on the electronic character of the substituents. Electron-donating alkyloxy groups are known to enhance the stability of DBAs. On the other hand

• , DBAs substituted with electron-withdrawing groups have been little studied [19], and their chemical stability and physical properties are not well understood. In this paper, a new DBA substituted with ester groups was synthesized, and the double azide addition was comprehensively investigated. Finally

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• of a variety of biologically important anions due to the presence of two pyrrolic NH hydrogen bond donors [38][39][40][41][42][43]. Notably, in the past few decades, the chemistry of DPMs have attested to be imperative in the existing chemical research because of their easy syntheses, good stability

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

• immobilization strategies, including covalent bonding and encapsulation, cater to different polymer types. Soluble polymers enhance diffusion, while insoluble ones ensure stability and high loading capacities [42]. Silica is also widely applied due to its ease of functionalisation and thermal stability [43]. The

• 39% ee for a pore size of 11.3 nm [64]. Catalyst supports must meet certain criteria, including being chemically inert, and the supported catalyst should exhibit high stability across various reaction conditions while also being easily recyclable [8][64]. When the solid support is not inert, it can

• reactions in a less protic and less polar solvent. Attaching catalysts to solid supports also offers the potential for enhancing catalyst stability. Boyer and co-workers reported the use of silica nanoparticle-supported eosin Y 21 as a photocatalyst in reversible addition fragmentation chain transfer (RAFT

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• -withdrawing group improves the stability of the product 4 (R = p-O2N-C6H4, E = PhSe) and also because phase separation is caused by the product precipitation from the reaction solution. On the other hand, the addition reaction of (PhTe)2 to isocyanides does not proceed at all [30]. This is because the

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

• field of computational chemistry and biochemistry: 1. AMBER [56]: AMBER (https://ambermd.org/) is the acronym for "Assisted Model Building with Energy Refinement", and it is an open-source software widely employed for molecular modelling and simulation. It is known for its stability, user-friendly

• scoring function based on the AMBER force field to evaluate the stability of the complex. DOCK is particularly useful for GAGs due to its ability to accurately model conformational flexibility and enhance sampling, allowing for more precise predictions of ligand–receptor interactions. 7. ATTRACT [138]: It

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• their synthesis have been extensively reviewed [93]. When hydrazones undergo cyclization with β-ketoesters or ketones, the stability of the enol form of the carbonyl compounds plays a crucial role in the reaction. Recognizing this, a series of multicomponent reactions has been developed to synthesize

• consecutive three-component approach in a polymer analogous fashion with diynes 105, terephthaloyl chloride (106), and hydrazines to synthesize high molecular weight pyrazole-based polymers 107 (Scheme 38) [132]. The materials 107 fluoresce in THF solutions, form thin films, and possess high thermal stability

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

• replaced by a pyrazole, which improves several aspects of their performance, including quantitative photoswitching between isomers and significantly enhanced thermal stability of the Z isomer [13][14][15]. This has led to recent reports on the integration of AAPs into surfactants to form systems with

• that Z–E isomerisation cannot be easily induced using gentle heating or visible light, as shown by the stability of the UV–vis absorbance spectra and SAXS patterns under these conditions (Figures S1 and S3, Supporting Information File 1). In contrast, irradiation with X-rays leads to significant

• stability of the Z isomer, AAP photoswitches are also susceptible to Z–E isomerisation on X-ray irradiation due to the presence of catalysing ionic and radical species from radiolysis of the surrounding water. This can be seen by a partial return of the UV–vis absorbance spectrum of AAPTAB from the Z to the

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• the aromatic product 85, thereby regenerating the catalyst (Scheme 16) [61]. Given its abundance, stability, and low price, elemental sufur (S8) is an ideal source of sulfur atom to produce thiacycles [62]. In 2019, H.-T. Tang utilized this reagent in combination with (hetero)aromatic ketone-derived

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• TFA), the stability of products 3 was a concern. Indeed, subjecting product 3a to the optimal reaction conditions with either AgNTf2 or Cu(NTf2)2 resulted in the significant degradation of 3a, although the degradation of 3a was partially suppressed when AgNTf2 was used (Scheme 1b). Accordingly, we

• . (a) Sequential π-Lewis acidic metal-catalyzed cyclization/photochemical radical addition for the formation of 1H-isochromene derivatives 3 and its plausible catalytic cycles. (b) Stability of 3a under the optimal reaction conditions of the batch reaction. The reaction with benzyltrimethylsilane

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

• -difluoroethylene was shown to have a lower energy compared to trans-1,2-difluoroethylene, which is in accordance with previously described 1,2-dihalogenated ethylene species [47]. The authors of reference [47] explained the higher stability of (Z)-HFO-1132 as follows: Within the family of 1,2-dihaloethylenes, when

• the methods for the preparation of HFO-1132 as well as reactions demonstrating the chemical behavior of this compound. From the reactions not included in this Review article, mechanistic studies on 1,2-difluoroethylene ozonolysis [77][103][104][105][106][107][108] and studies on the stability of

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• -conversion for the mono-brominated compound, we encountered several problems related to the stability of the product (see Supporting Information File 1). To circumvent these issues, we came across the possibility of inserting an oximino group into the benzylic position which can then be converted into an

• amino group by reduction. We reasoned that increasing the sp2 fraction and the rigidity of the whole structure will lead to increased stability of these derivatives. The first exploratory attempts demonstrated the easy preparation and the high bench stability of the oxime derivatives, therefore we opted

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

• the lower stability of the less-substituted β-lactam derivatives under thermolysis conditions. Additional alkyl substituents sterically shield the ring and prevent an unwanted nucleophilic attack leading to product degradation. In reactions with alcohols and mercaptans, the corresponding esters 3k–n,r

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• hydration reaction of carbon dioxide to bicarbonate, cyanates to carbamic acids, aldehydes to gem-diols, etc., and represent a potential therapeutic target for diseases like osteoporosis, edema, obesity or cancer [29]. Alım et al. [30] evaluated a series of thiophene sulfonamides based on the high stability

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• catalysts Noncovalent organocatalysts display a few advantages compared to the traditional metal Lewis acids, such as lower environmental impact, higher stability to air and moisture, easier removal from the GBB products. In this regard, Bolotin et al. in 2022 have reported the high catalytic activity of

• economy (water was the only byproduct) and thermal stability as well as remarkable fluorescence properties. Multicomponent reaction can be also employed to prepare crystalline porous materials namely covalent organic frameworks (COFs). The structural diversity and functionality of COFs were assembled from

• of COFs was further demonstrated by employing the 1,4-diisocyanobenzene (102) monomer, leading to the generation of four COFs 103 in 71–88% yield. The results showed that the synthesized COFs displayed good chemical and thermal stability (Scheme 32). 3.2 GBB-like reactions Basak et al. [68] reported

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• ‘Hückel Rule’ (a term that was actually introduced by Doering) [39] was originally developed solely for monocyclic systems, but was later extended by Vol’pin to cata-condensed polycyclic systems [40]. It is generally assumed that aromatic molecules are characterized by excess stability and a large Gap

• . Unsurprisingly, the (4n + 2) systems show higher Gap values (Figure 6B), however, the difference consistently diminishes until it is negligible for 10-ring systems. (For further analysis based on this criterion, including molecular stability, see section 1.4 of Supporting Information File 1.) Influence of atomic