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

• modification of 1d, representative of the large swath of chemical space accessible by Ugi-deprotect-cyclize (UDC) methodology, gave the dihydroquinoxaline 1g in good yield with high deuterium retention [29][30][31][32]. The catalytic three-component Ugi reaction was first reported by List in 2008 [33][34] and

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• HF is still inevitable [40][41]. Quite recently, Crimmin and co-workers reported gem-difluorination by shuttling between fluoroalkanes and alkynes, in which catalytic HF played a key role [42]. In the course of our study on the fluorination reaction, we have envisioned that the combination of a

Electrochemical allylations in a deep eutectic solvent

• Sophia Taylor and
• Scott T. Handy

Beilstein J. Org. Chem. 2024, 20, 2217–2224, doi:10.3762/bjoc.20.189

• limitation by using electrochemistry with catalytic amounts of metal or perhaps by recovering and recycling the metal with a recyclable solvent was the goal motivating this project. With this as a background, we undertook an investigation of electrochemical allylation in DES. Results and Discussion While

• reducing the waste generated in these allylations. While non-sacrificial graphite electrodes had failed to result in any reaction, it seemed possible that the use of a catalytic amount of tin metal or a tin salt with graphite electrodes would result in a superior reaction due to in situ reduction and/or

• . While the DES clearly had some ability to be recycled, the use of catalytic amounts of metal had uniformly failed. Recognizing that DES have been used extensively for electroplating and metal deposition, though it seemed that this might provide an opportunity for metal recovery and reuse [19]. To this

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

• ). Results and Discussion Reaction optimization Over the past two decades more than 300 various catalytic systems have been proposed for Biginelli chemistry, e.g., simple inorganic and organic acids, metal salts, metal oxides, ionic liquids, phosphines, nanocatalysts, organocatalysts, ion exchange resins [1

• , Leishmania amazonensis, Tcruzi epimastigota, Dengue larvicida, and for selected cases Alzheimer and Sars-COVID. For more details, see Table S1 (Supporting Information File 1). Conclusion In summary, we have demonstrated the catalytic regioselective Biginelli synthesis of new S-heterocyclic systems ‒ 4-aryl

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

• , providing a cost-effective alternative to traditional catalytic methods. The immobilisation of organocatalysts offers the potential to increase catalyst reusability and efficiency in organic reactions. This article reviews the key parameters that influence the effectiveness of immobilised organocatalysts

• , 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

• and an environmental perspective. An efficient catalytic process is characterised by the fact that the catalyst can be easily and, if possible, completely separated from the reaction mixture. Catalysts can be classified into homogeneous and heterogeneous catalysts. In homogeneous catalysis, the

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

• photoirradiation conditions (Scheme 3b). Thus, it was shown that the photoirradiated dithiolation of aliphatic isocyanides with (PhS)2 proceeded as a catalytic reaction of (PhSe)2 (30 mol %). In the dithiolation products 4 from aliphatic isocyanides, two PhS-groups were observed non-equivalently, suggesting the

• thioselenation and catalytic dithiolation of isocyanides. Synthesis of carbacephem framework. Sequential addition of (PhSe)2 to ethyl propiolate and isocyanide. Isocyanide insertion reaction into carbon-tellurium bonds. Radical addition to isocyanides with disubstituted phosphines. Radical addition to phenyl

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

• the ecological and economic requirements. This “ideal” synthesis would commence with simple starting materials, progress through safe, catalytic, and quantitative conversions, and culminate in streamlined processes, all conducted within a single reaction vessel. Multicomponent reactions (MCR) closely

• -oxodithioesters 48 react with primary or cyclic aliphatic amines, resulting in the formation of β-oxothioamides 50, which can then be directly converted into the corresponding 5-aminopyrazoles 49 with aromatic hydrazines in the presence of catalytic amounts of acetic acid (Scheme 14) [68]. The process exhibits

• intermediates undergo cyclization following a Michael addition to yield the corresponding pyrano[2,3-c]pyrazoles 63 (Scheme 20) [91]. Safaei-Ghomi et al. succeeded in isolating the intermediately formed pyrazole 64 [92]. Since pyrano[2,3-c]pyrazoles are fused heterocycles of interest, catalytic methods for

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

• to the closer proximity leading to more efficient transfer of the catalysing species between molecules [40]. This suggests that there is a breakdown in the efficiency of the catalytic transfer at the concentrations studied here, or there is a critical water concentration needed to produce a

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

• -diphenylethylene proceeded with similar efficiency, thereby excluding any radical pathway. As such, it was proposed that the catalytic electrooxidation of iodide (ENH4I = 0.41 V and 0.75 V vs Ag/AgCl in dimethylacetamide for I−/I3− and I3−/I2 redox couples) into iodine provided a green and mild tool to in situ

• aldehyde-derived hydrazones 114 and diarylphosphine oxide 115. The phosphorylation proceeded with slightly higher yield in the presence of a catalytic amount of manganese dibromide but its role was not clearly identified. Cyclic voltammetry analysis supported the initial oxidation of the hydrazone (Ep/2 of

• (Scheme 26) [76]. Electrochemical access to diazo compounds Diazo compounds are highly useful synthetic reagents in organic chemistry. For instance, they are regularly utilized as 1,3-dipoles in cycloaddition reactions or as precursor of carbenes under thermal, photochemical, and catalytic transition

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

• subsequent photochemical radical addition [46][47][48][49][50][51][52][53][54], which affords 1H-isochromene derivatives 3 through three catalytic cycles (Scheme 1a) [55]: catalytic cycles I and II and a photoredox cycle of the photocatalyst [56][57] (see Supporting Information File 1 for the overall

• catalytic cycles). In catalytic cycle I, the key cationic components, 2-benzopyrylium intermediates A, are generated in situ by the activation of the alkyne moiety of ortho-carbonyl alkynylbenzene derivatives 1 in the presence of the π-Lewis acidic metal catalyst [M]X [AgNTf2 or Cu(NTf2)2] and subsequent

• intramolecular cyclization followed by proto-demetalation with trifluoroacetic acid (TFA). In catalytic cycle II, photoexcitation of the generated 2-benzopyrylium intermediates A under light irradiation facilitates single-electron transfer (SET) from benzyltrimethylsilane derivatives 2 as the donor molecule

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• ) diacetate (PIDA) [22][23]. And more recently, Du and our group have developed a method for the chemoselective cycloisomerization of o-alkenylbenzamides to 3-arylisoquinolinones, using PhIO as oxidant in combination with a catalytic amount of trimethylsilyl trifluoromethanesulfonate [24]. Although

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

• tumor bed of a vast diversity of human tumor types. As phenylalanine is the preferred substrate of IL4I1 catalytic activity, Presset et al. [6] reported novel phenylalanine derivatives as a strategy to inhibit IL4I1 activity, as this enzyme has a preference for hydrophobic amino acids. Among them

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

• future perspectives of this reaction. Review 1 Novel synthetic methods The previously mentioned review, published in 2019 [1], had already highlighted how wide the variety of methods were used to conduct the GBB reaction: as much as 46 different catalytic systems had been reported in the literature at

• conditions can also be found. 1.1 Metal and Brønsted acid catalysts As previously mentioned, Sc triflate is the most widely used Lewis acid for the GBB reaction, generally exhibiting higher catalytic activity compared to other metal triflates, such as Yb, In or Bi. No extensive work had been done on rare

• , was not observed. In 2016, Sashidhara et al. reported the catalytic effect of Ag(OTf) on GBB reactions, postulating its role in activating the attack of the isocyanides onto the imine intermediates [7]; some years later Liu et al. reported a similar role of AgOAc [8]. Although the reaction was tested

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• was significantly enhanced when refluxing in DMF with a catalytic amount of AlCl3 compared to the reaction in clear DMF (Table 1, entries 7–9). Other Lewis acids were not as effective, except for a combination of DMSO/TMSOTf (Table 1, entry 4). The application of AcOH/PPA for the synthesis of 5

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• CloPt2, it was 24%. Structural alignment revealed RMSD values below 3 Å, meeting the minimum criteria for structural conservation (Table S3, Supporting Information File 1). Furthermore, the catalytic residues within the peptidase domains were confirmed. CloPt1 catalytic residues are Cys35 and His111; for

• CloPt2, they are Cys18 and His 92. These residues maintained a distance and structural positions like the catalytic residues in PCAT1 (where the catalytic residues are Cys21 and His99). A similar procedure was carried out for CloM1 and CloM2, leading to the identification of the closest sequences within

• domain from the clostrisin cluster). The latter contains the peptidase domain of CloPt1, as the complete ABC transporter was deemed too large to synthesize and express in this system. This strategy was functional in previous studies and retained catalytic activity without the rest of the transporter

Chiral bifunctional sulfide-catalyzed enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids

• Sao Sumida,
• Ken Okuno,
• Taiki Mori,
• Yasuaki Furuya and
• Seiji Shirakawa

Beilstein J. Org. Chem. 2024, 20, 1794–1799, doi:10.3762/bjoc.20.158

• ; enantioselectivity; halogenation; lactones; organocatalysis; Introduction Catalytic asymmetric halolactonizations of alkenoic acids are powerful methods for the preparation of important chiral lactones in enantioenriched forms [1][2][3][4][5][6][7][8][9][10][11]. A wide variety of chiral catalysts have been applied

• remained a formidable challenge in the field of catalytic asymmetric synthesis (Scheme 1b) [23][24][25]. To address this limitation, we have investigated the use of BINOL-derived chiral bifunctional sulfide catalysts, which were developed by our group [10], in asymmetric bromolactonizations of α

• -substituted 4-pentenoic acids without additional substituents on the carbon–carbon double bond (Scheme 1c) [26][27]. Chiral α-substituted γ-butyrolactone products as important building blocks for pharmaceutical development were obtained in a highly enantioselective manner in our catalytic system using

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• moiety under the influence of water. The appearance of HCl in these cases was identified by the specific odor and detected by pH measurements. It is likely that this catalytic amount of HCl is enough for the conversion and formation of the amides 10. To confirm the influence of HCl and its necessity to

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• radical (potassium nitrosodisulfonate) [13] or catalytic systems like methyltrioxorhenium(VII) (MeReO3) [14] and 2-iodobenzenesulfonic acids (IBS)/Oxone® [15] led to either p-quinones or o-quinones, depending on the substituents in the para-position to the hydroxy group. Recently, hypervalent iodine

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• -lactone motif on an estradiol backbone [17]. Beginning with the 7α-alkanamidoestrone derivative 17, a nucleophilic addition by the anion of the THP propargyl ether occurred stereoselectively and provided the alkyne 18 in a 75% yield. Afterwards, the catalytic hydrogenation of the alkyne with a 1:1 mixture

• steroidal 17-ketones were first alkylated in the presence of the lithium derivative of ethyl propiolate. After stereoselective formation of the corresponding adduct, the triple bond was chemoselectively reduced under catalytic hydrogenation using 5% palladium on charcoal. As a final step, a p

• process, the carbonyl group at C-17 was stereoselectively attacked by α-lithio-α-methoxyallene at −78 °C to produce allene 25. A further cyclization reaction was induced by potassium tert-butoxide in the presence of catalytic dicyclohexyl-18-crown-6. The final 17-spirodihydro-(2H)-furan-3-one 27 was

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• "catalytic promiscuity" would enhance the utility of enzymes as synthetic tools and facilitate rapid access to a diverse array of natural product analogs through integration with chemical synthesis [108]. Conclusion In this review, recent advancements in the field of chemo-enzymatic total synthesis were

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• (Mg2+-dependent, metal-independent, cobalamin-dependent), common structural folds (class I–V, with class I being the largest group, characterised by the Rossmann fold) [58], or catalytic mechanism (SN2 mechanism, radical mechanism, Figure 3) [59]. This review categorises RiPP MTs based on the acceptor

• oxygen-independent coproporphyrinogen-III oxidase (CPO). B) Catalytic mechanisms of rSAM-mediated methylation are depicted exemplary for class B (TsrM) and class C (TbtI) RiPP MTs. The three-dimensional structures of the rSAM C-MTs TsrM with bound cobalamin and [4Fe-4S] cluster (PDB ID: 6WTE (https

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• and cloned from deep-sea-derived Microbulbifer sp. JAMB-A94 with pH and temperature optima being 7.0 and 55 °C, respectively [26]. The recombinant enzyme was likewise produced using a B. subtilis host. The crystal structure of the catalytic domain was determined to show a β-jelly roll fold with

• exochitinases. Genomic analysis of a marine Microbulbifer degradans 2-40 revealed three chitin depolymerases (ChiA, ChiB, and ChiC) [117]. ChiB was cloned and expressed in E. coli [22]. It is a modular protein that is predicted to contain two GH-18 catalytic domains, two polyserine domains, and an acidic repeat

• domain. It functions as an exochitinase. The two catalytic domains have different activities on chitooligosaccharides. Each domain was maximally active from 30 °C to 37 °C and from pH 7.2 to 8.0. Both domains function cooperatively to degrade chitin [22]. It should be noted that M. degradans 2-40 was

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• by Blackburn and coauthors [20]), HClO4, and TsOH. We wanted to avoid the use of HClO4 in our parallel reaction set-up, so that only two remaining catalytic systems were evaluated. 580 library members were deliberately selected for both reaction conditions, and the corresponding experiments were

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• anilines were obtained. The quinoline reduction was efficiently promoted by adding a catalytic amount of p-toluenesulfonic acid (PTSA) or pyridinium p-toluenesulfonate (PPTS). Pyridine was also reduced to piperidine in the presence of PTSA. Keywords: cyanoarene; nitroarene; PEM reactor; pyridine

• by the equilibrium (Figure 2). Based on this hypothesis, we examined several acids and found that the addition of a catalytic amount (0.10 equiv) of p-toluenesulfonic acid (PTSA) was sufficient (Figure 3). The first run gave 7a in 88% yield and the second run with the MEA gave 7a in 85% yield. MEA

• low and 8a·PTSA was obtained as the major product (60% yield), suggesting that the catalytic amount of PTSA was not sufficient because it would be completely trapped with 9a. These results suggest that stoichiometric amount of PTSA was required to liberate 8a from the membrane. As expected, the yield