N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• indirubin-N-glycosides Thioindirubin-N-glycososides In our group, we studied the reaction of isatin-N-glycoside 16a with thiaindan-3-one which afforded red colored thioindirubin-N-rhamnoside β-32a in very good yield and with excellent Z-selectivity (Scheme 20) [26]. Deprotection of β-32a afforded β-33a in

• excellent Z-selectivity (Scheme 23) [38]. Deprotection of β-37a gave β-38a in very good yield. Likewise, rhamnosides β-38b–d, mannosides β-33e–g, and glucoside β-38h were prepared. The reaction of 36f with isatins 39a–h afforded novel non-glycosylated selenoindirubins 40a–h (Scheme 24) [38]. In

• coumaranone carbonyl group resulting in a downfield shift in case of the Z-isomers. The different E/Z-selectivity in case of oxoindirubins as compared to other indirubin derivatives can be explained, on the one hand, by the absence of the favorable intramolecular hydrogen bond which is present in case of

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• detecting aqueous H2S are in development [8][9][10][11][12][13][14], lack of sensitivity, selectivity, and cost effectiveness remain major challenges. For a number of years we have explored the properties of lanthanide-based chemosensors (Ln = Eu3+ or Tb3+) due to their significant advantages over

• removal of Na2S followed by the precipitation and re-addition of Cu2+ ions (Figure 5). Comprehensive selectivity studies were conducted with various anions/sulfur compounds (SO42−, SO32−, S2O52−, S2O42−, S2O32−, ClO−, OAc−, NO3−, I−, HCO3−, CO32−, Cl−, lipoic acid, and glutathione, as depicted in Figure 6

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• footprint of organic reactions [12][13]. Beyond environmental benefits and enhanced human safety, mechanochemical reactions often feature shorter reaction times, eliminate the need for external heating, and offer alternative product selectivity [3][14]. In general, such reactions are characterized by the

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• catalytic center; finally, the selectivity affording E-enyne and Z-enyne product is also an issue to be addressed, and possible side reactions need to be suppressed (Scheme 2). In this review, we summarize the recent development of copper-catalyzed yne-allylic substitutions. It is worth noting that when we

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• catalyst efficiency and selectivity in sustainable chemistry applications. Keywords: asymmetric catalysis; carbon dioxide; CO2; epoxide; frustrated Lewis pairs (FLPs); volcano plot; Introduction The field of frustrated Lewis pairs (FLPs) has flourished since their seminal discovery in 2006 by Stephan and

• was engineered to produce a single enantiomer preferentially from both enantiomers of the epoxide substrate. An enantiomeric excess of 95%ee was initially achieved, with the predominant (R) enantiomer. Enhanced selectivity was subsequently observed through additional transition states, resulting in a

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• (at 10–30 nM) of the CLK1, CLK2 and CLK4 kinases, and a remarkable selectivity since it does not show any action (at 100 μM) against the closely related DYRKs kinases [2][3]. Very recently, this skeleton proved to be also very useful in the research of antimicrobial agents [4], and the closely related

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• air under mild conditions. Therefore, many triarylbismuthines could be used to form a variety of useful arylboronates in moderate to good yields with excellent product selectivity. We hope that this new approach to the generation of aryl radicals from triarylbismuthines will lead to an increased use

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

• C–H hydroxylation process by combining continuous flow chemistry and electrochemistry (Scheme 8) [16]. The surface modification of electrodes can lead to improved reactivity and selectivity. In this regard, Li and coworkers developed electron-deficient W2C nanocrystal-based electrodes to enhance the

• celestolide showed high yields and good selectivity (Scheme 9). The Lei group also disclosed another C(sp3)–H functionalization involving C–O-bond formation [18]. The reported method allows the straightforward preparation of α-acyloxy sulfides from ubiquitous carboxylic acids and sulfides, providing an

• oxidation then yields the intermediate. Subsequent desilylation and substrate/product exchange complete the catalytic cycle (Scheme 40). This approach underlines the potential of asymmetric electrosynthesis in achieving high selectivity and efficiency in complex molecule synthesis, further broadening the

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• production as a result of the expensive cost of Ni-DVBP and Ag/AgCl electrode, low surface-to-volume ratio, ineffective mixing, and sluggish heat exchange. The longer inter-electrode distances, may also lead to longer reaction times and poorer reaction selectivity and decreased yields [21]. Jeremy Robertson

• reaction selectivity [25]. Continuous flow technology has emerged as an attractive solution for many of these challenges, gaining popularity for its ability to efficiently address these issues. Additionally, this platform offers the advantage of integrating multiple steps, i.e., performing multistep

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• and local models to guide the design of synthetic processes. Global models exploit the information from comprehensive databases to suggest general reaction conditions for new reactions, while local models fine-tune the specific parameters for a given reaction family to improve yield and selectivity

• volumes of data and accelerate the prediction of optimal reaction condition combinations. It has been widely demonstrated that ML algorithms can be used for various chemistry-related tasks, such as yield prediction [14][15], site-selectivity prediction [16][17], reaction conditions recommendation [18

• ][116][117], regioselectivity, and site-selectivity [16][17][118][119][120]. However, this approach is also computationally demanding and requires a good initial guess of the TS structure. Moreover, it may face difficulties in simulating some classes of reactions and large-size molecules [121], and the

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

• ]. The reaction time and temperature were reduced from >2 h and 80 °C in industrial operation to 10 min and 65 °C in the microreactor with high conversion and selectivity. Since O-methylisouronium sulfate can be dissolved in high concentrations of sulfuric acid, it is expected to construct a homogeneous

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• simultaneous construction of homoallylamine scaffolds, exemplified by compounds 16–20 with up to 3 contiguous stereocentres, including a quaternary centre in moderate to high yields (60–94%) with 90–99% ee and dr in the range from 97:3 to >99:1 (Scheme 4). The selectivity of the reaction arises from the

• 24, which supported the hypotheses regarding the selectivity-determining transition states arrangement. It is important to note, that boronic acids 14 are highly sensitive to oxidation by air and could only be purified in air-free conditions and stored in airtight containers. Additionally

• give the desired product 99 after 72 h returning hemiaminal (Scheme 21). Alkyl acetals, such as cyclohexyl carboxaldehyde acetal reacted sluggishly with low yield and selectivity (<10% yield, 43–50% ee), possibly due to their inability to participate in π–π interactions. In general, the π-stacking

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

• -based catalytic system for the highly stereoselective addition of various bisthiomalonates to chalcones and dienones [29]. While recognizing the potential for greater selectivity enhancement and time savings with ball milling, hydrogen-bonding catalysis was effective only with aromatic enones, yielding

• planetary mill. Further variations of system A concerned the acid’s role. However, no impact of the acid was noted while using the amino acid derivative AC-2, but the dramatic loss of selectivity was observed in the case of chiral phosphoric acid’s application AC-3. Thus, it is rather unlikely the iminium

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

• decades have showed an increased interest from the community. This review gives an overview of the work in the field of ML in organocatalysis. The review starts by giving a short primer on ML for experimental chemists, before discussing its application for predicting the selectivity of organocatalytic

• . Keywords: catalyst design; machine learning; modelling; organocatalysis; selectivity prediction; Introduction Since the beginning of the 21st century, organocatalysts [1] have established themselves as a third group of homogeneous catalysts, next to biocatalysts [2] (enzymes) and transition metal-based

• energies of relevant species either via force field or quantum chemical methods to assess the properties of a reaction such as activation energies or selectivity. Irrespective of the degree of automation, in silico calculations are often less time-sensitive than wet-lab experiments and can be used to

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• thioesters and β-keto amides by simply changing reaction conditions. These features, including a good substrate scope, excellent yield and selectivity and ease of scale-up, rendered the green hydrolysis reaction very environment-friendly, practical, and attractive. Experimental 1H and 13C{1H} NMR spectra

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• acidic conditions since such conditions enhance the selectivity, so various catalysts, mainly acidic, were tested for the model Biginelli reaction and the results are shown in Table 1. One of the most effective promoters for this type of reaction is TMSCl [29][30][31] and we also tried to involve TMSCl

• (Table 1, entry 7). Reflux in alcoholic media in the presence of p-toluenesulfonic acid or CAN (ceric ammonium nitrate) was also not particularly successful (Table 1, entries 8 and 9, yield 32–35%). We subsequently explored a range of reaction conditions to improve overall yield and selectivity. We

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

• , including the type of support, immobilisation techniques and the resulting interactions. In addition, the influence of these factors on catalytic activity, selectivity and recyclability is discussed, providing an insight into optimising the performance of immobilised organocatalysts for practical

• reaction components and the catalyst are in the same phase. Active catalytic sites are readily accessible to the reactants and therefore generally result in higher catalytic activity and selectivity [8]. As a result, homogeneous catalysis is generally preferred to heterogeneous catalysis, especially in the

• influence on the properties and thus performance of the resulting heterogeneous catalyst. However, immobilisation and structural modification introduce additional steps in the synthesis of the catalyst. Moreover, the catalytic activity and selectivity of immobilised catalysts are often lower than those of

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• their ability to be engaged in such a rearrangement [4][5]. Upon activation with trifluoromethanesulfonic anhydride and under heating, we showed their transformation to ortho thioethers with a fairly acceptable selectivity towards the pathway of sulfilimine synthesis (Scheme 1b). Following our seminal

• arenes in good yield. Inspired and stimulated by this abundant literature, and as part of our research program focused on creating novel perfluoroalkylsulfur derivatives, we became interested in a reappraisal of our previous study with the aim of increasing its scope as well as the yield and selectivity

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

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

• phosphane ligands is crucial for the selectivity in this reaction. Suzuki coupling can also serve for the functionalization of iodochromones 55, which, as α,β-unsaturated ketones, undergo ring opening under the reaction conditions, followed by Michael addition–cyclocondensation. Xie et al. devised a method

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

• reaction conditions to selectively oxidize the desired compound. In some cases, the use of an electromediatior such as an iodide anion helped in achieving the desired selectivity. In line with the continuing increasing interest for both electrosynthetic organic transformations and the chemistry of

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• presented. We also discuss the selectivity of the radical addition to Ni(II) norcorroles using DFT calculations. Results and Discussion Reactivity with azo radical initiators We selected 2,2'-azobis(isobutyronitrile) (AIBN) as a radical source. Ni(II) dimesitylnorcorrole 1 was treated with AIBN in refluxing

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• employed as nucleophiles in chemical transformations, and a mixture of both N1- and N2-alkylated products is formed, depending on the reaction conditions, with little selectivity in regards to substituent effects [27][28][29][30][31][32][33]. Considering the importance of indazoles as a widely used

• for N1/N2 discrimination studies. The existing approaches for generating N-substituted indazoles of compound 6 often lead to a mixture of N1- and N2-alkylated indazoles with either low selectivity or moderate yields depending on the conditions used. For example, Takahashi et al. obtained N1- and N2

• -substituted indazole analogs in 44% and 40% yields, respectively, by treating compound 6 with methyl iodide and potassium carbonate in dimethylformamide (DMF) at room temperature for 17 h [40]. Other works have shown poor selectivity when 6 and other isomers similar to 6 were reacted with isopropyl iodide and

A new platform for the synthesis of diketopyrrolopyrrole derivatives via nucleophilic aromatic substitution reactions

• Vitor A. S. Almodovar and
• Augusto C. Tomé

Beilstein J. Org. Chem. 2024, 20, 1933–1939, doi:10.3762/bjoc.20.169

• synthesis of highly fluorescent DPP derivatives through straightforward nucleophilic aromatic substitution reactions with thiols and phenols. These nucleophilic substitutions occur at room temperature and manifest a remarkable selectivity for the 4-position of the pentafluorophenyl groups. Both symmetrical

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

• ][28]. However, the selectivity of these photoredox reactions is driven by the structural properties of the heteroaromatic ring. During the preparation of this article, the Meggers group published an outstanding enantioselective iron-catalyzed α-amination pathway (Scheme 1b) [29]. The method is widely