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

• than two chiral centers were not included. This resulted in 271,026,660 library members with nearly 85% expected synthetic accessibility according to the model experiments described in the previous section. Distributions of the resulting chemical space over molecular weight (MW), 1-octanol–water

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• ][40]. Photoresponsive supramolecular amphiphiles are responsive, complex, and adaptable in aqueous medium [41][42][43]. Supramolecular assemblies of photoresponsive molecular amphiphiles in aqueous medium can undergo transformation in solution or at the air–water interface and even sustained

• were investigated in aqueous medium. An aqueous solution of 5.0 wt % DA11 in Milli-Q water was prepared, followed by deprotonation with 1.0 equivalent of NaOH, showing excellent solubility up to 93 mM, giving a deep purple solution. An aqueous 43 µM solution DA11, diluted from the 5.0 wt % stock

• source (380–800 nm, 300 W) positioned at a distance of 1 cm from the sample. Preparation of aqueous samples All aqueous solutions of DAn were prepared according to the following general procedure: DAn (5.0 wt %) was mixed with 1.0 equivalent NaOH in Milli-Q water. The obtained aqueous solution was

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• only slightly more stable than the other three conformers in both the gas phase and implicit water [4]. Hence, it appears that strong intramolecular interactions, and not only hydrogen bonding, govern the orientation of the fluorine atom in the F‒C‒C‒N fragment, favoring the cis-isomer of 3

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

• ). To ensure the capture of 2a, we performed reduction with phosphoric acid (pKa = 2.12). Although the generation of 3a was suppressed, only a trace amount of 2a was obtained, and almost 1a was recovered (Table 2, entry 4). This was probably because the presence of water inhibited the reaction

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• . After the extractions were finished and dried by rotary evaporation, the extract was resuspended in basic water (pH 10 using NaOH) and vacuum filtered to remove insoluble particulates. Liquid–liquid extraction was performed three times with basic water and DCM. The DCM layer was collected and dried

• . Afterward, the extract was resuspended in 0.1% formic acid in water. A Combiflash EZ prep system was used to purify the burpitides from C. americanus. Water with 0.1% formic acid (A) and methanol (B) were used as solvents for a reversed phase column (C18 21 × 250 mm Kinetix 5 µm C18 100 Å (00G-4601-P0-AX5

• min, 5% B; 13 min, 5% B where solvent A was water with 0.1% of formic acid and solvent B was acetonitrile with 0.1% of formic acid. A top 5 HCD method at 25 NCE (200–2000 m/z) was used on each plant tissue extract. See Supporting Information File 1, Table S2 for complete acquisition parameters. The

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

• nucleophiles, including water to give benzylic alcohols, or methanol to give methoxy products. Musacchio and co-workers reported a similar approach for benzylic fluorination (Figure 33) [84], which followed a similar mechanistic blueprint to that reported by the Doyle group. Using tert-butoxide radicals

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• residual water during column chromatography. Unfortunately, attempts to assign the absolute configuration of products 5 failed, as we have not been able to obtain any crystals suited for single crystal X-ray diffraction analysis. Finally, we also tested the suitability of products 5 to access acyclic α-AA

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• is introduced on the azobenzene to increase the water solubility. The influence of ortho, meta, and para-substitution patterns of the azobenzene on the lectin binding has also been studied. Synthesis The β-O-galactosyl p,p'-bis-substituted azobenzene derivative 1 was prepared from galactose and

• commercially available p,p’-dihydroxyazobenzene (6), by using our recently developed DMC (2-chloro-1,3-dimethylimidazolinium chloride)-mediated one-pot glycosylation method in water [28], followed by O-alkylation of the remaining hydroxy group with BrCH2CH2NHBoc and acidic deprotection (Scheme 1). Three

• respectively 71%, 41%, and 37% total yields (Scheme 1). Photophysical characterization The photoswitching properties of galactosyl azobenzenes 1–5 were realized in water or in Tris buffer containing 5 to 10% DMSO, in accordance with the biophysical evaluation conditions by using ITC. All these compounds

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• molecular sieves as water scavengers, but it showed no positive influence on the reaction efficiency (Table 1, entry 20). It should be noted that no competing aza-Michael adduct was monitored in all of the evaluated reaction conditions. According to the above screening results, the generality of the

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• rearrangement using benzonorbornadiene and the chiral natural compound (+)-camphene as bicyclic alkenes, selectfluor as an electrophilic fluorine source, and water and various alcohols as nucleophile sources. The structure of bicyclic oxy- and alkoxyfluorine compounds was determined by NMR and QTOF-MS analyses

• materials, supramolecular and bioactive compounds [13][14][15][16][17]. To the best of our knowledge, although the oxyfluorination of various olefins with water and alcohols is known in the literature [18][19][20][21][22][23][24][25][26], there is no systematic study on the oxyfluorination of bicyclic

• alkenes. We previously developed a dihomohalogenation method using selectfluor as an oxidant [27]. Herein, we synthesized bicyclic oxy- and alkoxyfluorine compounds using selectflour as an electrophilic fluorination reagent, water and various alcohols as an nucleophile. Results and Discussion In this

Synthesis of cyclic β-1,6-oligosaccharides from glucosamine monomers by electrochemical polyglycosylation

• Md Azadur Rahman,
• Hirofumi Endo,
• Takashi Yamamoto,
• Shoma Okushiba,
• Norihiko Sasaki and
• Toshiki Nokami

Beilstein J. Org. Chem. 2024, 20, 1421–1427, doi:10.3762/bjoc.20.124

• current conditions until 1.2 F/mol of total charge had been consumed. Then, the reaction temperature was elevated to 0 °C, and this temperature was kept for 1 h. The reaction was quenched with Et3N (0.5 mL), and the reaction mixture was dissolved in EtOAc and washed with water to remove electrolyte. It

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• yield of 6 was observed alongside a decreased yield of 5, in all those cases that required prolonged reaction times (24–30 h). This event led us to suppose the formation of carbinolamine 6 from N,O-aminal 5 owing to the nucleophilic attack of a water molecule, probably caused by the enriched moisture

• catalytic cycle. Similar to what was previously observed, the elimination of the trichloro(alkoxy)ferrate(III) anion from intermediate C provides the iminium ion D, susceptible to nucleophilic attack by a water molecule present in the reaction medium, leading to the carbinolamines 6. This latter synthesis

• line with the values found for the slower reactions previously described (compounds 6b,d,g,i,n–p). By adding 500 μL of water to the medium the cyclization did not proceed, and the starting material 4j was recovered unchanged (experiment B, Scheme 5). This observation seems to suggest that the presence

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• aromatic and aliphatic alkynes 20a–h in a copper-catalyzed azide–alkyne cycloaddition (CuAAC). All attempted reactions could be conducted under standard conditions using copper sulfate and sodium ascorbate in THF/water (depicted in Scheme 3 and Figure 2). For selected derivatives, 21sd and 21vg, crystals

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• reaction [30][31]. Daemi et al. employed polyurethane nanomicelles as an eco-friendly and efficient polymeric ionic solvent [32]. Morooka et al. used supercritical water for the catalys-free Cannizzaro-type reaction of acetaldehyde [33]. Thus, the originally developed Cannizzaro reaction was subjected to

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• of water on the considered recyclization. So, carrying out the process in 80% aqueous EtOH resulted in a diminished yield (Table 1, entry 16). Thus, optimal conditions for the investigated recyclization are the application of K2CO3 in EtOH at reflux for 2 h. The elaborated conditions allowed us to

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• reactions in water due to the remarkable lack of water solubility of the highly hydrophobic aminofurans selected in this study. Therefore, the decision was made to perform these reactions using vegetable oil as an alternative green solvent system. For this purpose, SSO, OO, OA and LM, which can act as

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• the formation of the phenyl tosyloxy iodonium intermediate A from catalytic HTIB. Dialkyl bromoalkene 1 then associates with A followed by attack of tosyloxy or water, delivering iodonium intermediate B. Being a better leaving group, the bromide anion is then expelled, which becomes a counterion for

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• crude form for the next step. Treatment of the latter with triethylamine in methanol resulted in ring-cleavage to give intermediate E. Subsequent base-mediated Knoevenagel reaction with extrusion of water gave intermediate F which underwent lactonization and resulted in the formation of the final

• intermediate AE. Attack of the imine to the carbonyl group and subsequent extrusion of water afforded product 40. The reaction proved to be rather general and a variety of substituted 3-cyanochromones were successfully employed. 1,3-Bis(silyloxy)-1,3-butadienes The two-step reaction of 3-cyanochromones 16a–h

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• analyzed on a Waters HPLC system equipped with a 1525 pump and a 2487 dual λ UV detector using an Agilent ZORBAX SB-C18 reversed-phase column (5 μm, 4.6 × 250 mm) or a SilGreen C18AB reversed-phase column (5 μm, 4.6 × 250 mm). The elution solvents were water with 0.1% (v/v) trifluoroacetic acid (solvent A

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• in a terpene hydrocarbon, or through nucleophilic water attack, yielding a terpene alcohol [5]. To date, about 80,000 terpenes and terpenoids have been discovered [3], approx. 10% of which are sesquiterpenes, composed of 15-carbon skeletons [6][7]. Sesquiterpenes are mainly distributed in plants and

• (Scheme 1) [16]. As an alternative to deprotonation, the germacradienyl cation can be captured by water to yield the sesquiterpene alcohol hedycaryol, which is an important intermediate towards the synthesis of sesquiterpene alcohols [17]. The reprotonation of (R)-(+)-1 germacrene A or hedycaryol at the

• diols by addition of water. For each of these intermediates, simple deprotonation or nucleophilic attack by water are possible. Also, hydride shifts can occur first, which widens the chemical space of possible products. Additionally, the presence of multiple stereocenters adds to the rich

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• heavy metals, the use of bismuth compounds to promote reactions has the advantages of low cost and insensitivity to water and air. As such, the handling does not require special experimental techniques, such as an inert atmosphere and anhydrous solvents [55]. The use of bismuth salts in organic

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• friendly and atom-economical process for C–C and C–N bond formations utilizing alcohol as an alkylating agent and hydrogen donor, producing water as the only side-product [6][7][8][9]. Notably, alcohols are inexpensive, abundant and can be obtained from biomass, which makes this method even more attractive

• amount of t-BuOK (20 mol %) in t-AmOH at 135 °C for 24 h allowed for the investigation of several alkyl and aryl ketones with amines and vicinal diols yielding good to excellent yields of the desired pyrroles (Scheme 70) with water and hydrogen gas being the only byproducts. DFT calculations suggested

Kinetically stabilized 1,3-diarylisobenzofurans and the possibility of preparing large, persistent isoacenofurans with unusually small HOMO–LUMO gaps

• Qian Liu and
• Glen P. Miller

Beilstein J. Org. Chem. 2024, 20, 1099–1110, doi:10.3762/bjoc.20.97

• mL glacial acetic acid. After attaching a reflux condenser, the mixture was heated to reflux for 12 hours with stirring. The hot reaction solution was filtered. To the hot filtrate was added 5 mL of cold water leading to the precipitation of crude product. The crude product was vacuum filtered

• , washed with 5 mL water, and then air dried to give 3 as a white solid (57 mg, 60%, Scheme 3). Mp 169–170 °C (from [13], 188–189 °C); 1H NMR (500 MHz, CDCl3) δ 7.15–7.08 (m, 2H), 6.98 (s, 4H), 6.86–6.79 (m, 2H), 2.35 (s, 6H), 2.12 (s, 12H); 13C NMR (126 MHz, CDCl3) δ 143.54, 139.17, 138.71, 128.23, 127.43

• mmol), zinc dust (1.15 g, 17.6 mmol) and 13 mL glacial acetic acid. After attaching a reflux condenser, the mixture was heated to reflux for 12 hours with stirring. The hot reaction solution was filtered. To the hot filtrate was added 5 mL of cold water leading to precipitation of crude product. The

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• characterised as the most potent inhibitor of human CDA, but the quick degradation in water limited the applicability as a potential therapeutic. To improve stability in water, we synthesised derivatives of phosphapyrimidine nucleoside having a CH2 group instead of the N3 atom in the nucleobase. A charge

• -neutral phosphinamide and a negatively charged phosphinic acid derivative had excellent stability in water at pH 7.4, but only the charge-neutral compound inhibited human CDA, similar to previously described 2'-deoxyzebularine (Ki = 8.0 ± 1.9 and 10.7 ± 0.5 µM, respectively). However, under basic

• cytosine deamination involves a nucleophilic attack at the C4 position by a Zn2+-activated water molecule [40][41][42], it was proposed to employ transition state analogues and mimetics of the tetrahedral intermediate formed as inhibitors of these enzymes [43][44][45][46][47]. More than 30 compounds have

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• positions (Equation 3). In the context of the radical process, it is noteworthy that a standard household LED lamp can serve as an efficient initiator, capable of triggering bromine photolysis (Equation 3, top) [45]. Hence, no oxidant-derived residues apart from water are formed and, at the end of the

• reaction time (4 h overall, entries 3 and 4 in Table 1). In these last experiments a whitish solid appeared during addition of the oxidant, initially observed in the one with lower water amount (Table 1, entry 3). The 1H NMR confirmation of the nature of the solid as 3a, makes clear that phase separation

• reaction time (Table 1, entry 7), giving total conversion and excellent selectivity toward 3a. Water is an essential constituent of the system, as its polar nature favours the extraction of HBr from the organic phase, resulting in a useful shift of the reversible hydrogen abstraction from the substrate