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

• different compounds containing the indanone moiety. Synthesis of unsaturated β-ketoesters (Knoevenagel derivatives). aIsolated yield after purification using silica gel column chromatography. Synthesis of 3-aryl-2-ethoxycarbonyl-1-indanones mediated by bismuth triflate. aIsolated yield after purification

• decarboxylation directed by bismuth triflate at 100 °C. Synthesis of 3-aryl-1-indanones. aIsolated yield after purification using silica gel column chromatography. bReaction performed at 60 °C. cFrom tert-butyl Knoevenagel derivative. Basic protocol: The Knoevenagel product 9 (0.5 mmol), dry acetonitrile (2 mL

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

• obtained using a solvent purification system (Innovative Technologies, Inc.) and handled under a nitrogen atmosphere, unless otherwise noted. Flash chromatography was performed using SiliaFlash® F60 40–63 µm (230–400 mesh) 60 Å silica from Silicycle Inc. and RediSep® Rf Silica Flash Columns (12 g, 24 g or

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

• basic conditions. Compound 3 was obtained nearly on a 20 g scale in 89% yield after purification by sublimation in vacuo. In the presence of a catalytic amount of AIBN, compound 3 reacted with bis(trimethylsiloxy)phosphine (4) that was prepared in situ [66]. Treatment of the reaction mixture with MeOH

• obtained in 84% yield after silica gel purification. Removal of the Boc protecting group from 6 in the presence of trifluoroacetic acid in DCM at room temperature overnight, followed by cyclisation in boiling pyridine/triethylamine, led to 4-hydroxy-1,4-azaphosphinan-2,4-dione (7) in 84% yield. The free

• than 90% purity, as determined by 31P NMR. Compound 10 was used in the next step without further purification. A linear amide 11 was obtained in 47% yield by reacting phosphinate 10 with chloroacetamide in the presence of a large excess of HMDS in acetonitrile at 70 °C for two days. A cyclisation of

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• , for example a formyl group. Thus, the key isonitroso compounds 7 were synthesized from chlorides 1a–c via in situ formation of pyridylacetoacetic esters 2a–c followed by decarbonylation to give 2-methyl-3-nitropyridines 5a–c [24] which were used in the next step without purification. Their reactions

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• 13. The solvent 1,4-dioxane is crucial to the synthesis and purification in the initial two steps as other solvents such as THF make the purification process more intricate. This sequence is followed by SNAr with ammonia (29% v/v) to obtain building block diaminopyrazine 12. The synthesis of

• 12 under standard boiling acetic acid conditions, as reported in Scheme 1. The crude product could be collected via vacuum filtration, followed by additional purification via recrystallization from boiling DMF to afford golden crystals of 4a in moderate yields. In order to access 5a and 6a, a

• pressure worked well for the purification step to achieve an excellent 80% yield. To our delight, 5a did not require any additional purification under the same reaction conditions. Next, several unsuccessful synthetic efforts were made to access 7a using starting material 7e and building block 12, listed

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• the reported procedures [41], the Ugi-azide reaction of 2-bromobenzaldehyde (1a, 1 mmol), allylamine hydrochloride (2, 1 mmol), trimethylsilyl azide (3, 1 mmol) and tert-butyl isocyanide (4a, 1 mmol) in MeOH at 40 °C for 24 h afforded 1,5-DS-1H-T 5a in 92% yield after chromatography purification. Our

• purification. Thus, to the solution of crude 5a dissolved in MeCN (3 mL) were added 10 mol % of Pd(OAc)2, 20 mol % of PPh3, and 2 equiv of K2CO3 and the mixture stirred for 3 h at 105 °C under N2 atmosphere to give the desired product 6a in 60% isolated yield (entry 17 in Table 1). With the optimized one-pot

• . The initial Ugi-azide four-component reaction constructs the tetrazole motif while the subsequent intramolecular Heck reaction assembles the tetrahydroisoquinoline. The one-pot reaction avoids the intermediate purification which has favorable PASE in the synthesis of heterocyclic compounds

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• performed on a Bruker Apex Kappa-II CCD diffractometer. The solvents used, dimethyl sulfoxide and 1,4-dioxane, were purchased as dry solvents and applied without further purification. Other reagents, catalysts, ligands, acids, and bases were used as purchased from commercial suppliers. Column chromatography

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• intramolecular crossed [2 + 2] cycloaddition strategy (Scheme 4C) [36]. They were able to avoid purification by column chromatography by transformation of BCH ester (±)-53 into BCH acid (±)-54, allowing isolation of pure 1,2-BCH (±)-54 by crystallisation. Through their synthesis they were able to access both

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• grade and contained 0.1% vol/vol formic acid. Protein expression and purification The vectors to express Vs NnlA and H73A Vs NnlA were previously reported [21]. Pd, Mr, Ms, Ps, and Pj nnla genes were synthesized as E. coli codon-optimized constructs and cloned into the NdeI and XhoI restriction sites of

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• , yielding 4 with 90% yield and 99% conversion. A drawback of the Rolla protocol is the cost associated with the phase-transfer catalyst, and that the crude mixture requires purification through distillation or column chromatography. Another inconvenience is the high reaction temperature which limits the

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• temperature under argon. Under these reaction conditions, the tris(carboranyl)-substituted porphyrin 6 was obtained in 39% yield after purification by column chromatography on SiO2 using CHCl3/hexane 1:1 as eluent (Scheme 3). It should be noted that the reaction of porphyrin 6 with NaN3 in DMSO at 20 °C for

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• gene coding for the glutamate decarboxylase from Escherichia coli K12 (accession no. AAA23833) was cloned through homologous recombination in yeast into the expression vector pYE-Express [26]. Heterologous expression and purification of the recombinant enzyme (Figure S1, Supporting Information File 1

• ) allowed for test incubations with unlabelled glutamic acid in the presence of the cofactor pyridoxal phosphate (PLP), showing the complete conversion of glutamic acid (3) into γ-aminobutyric acid (4) (Scheme 2). The crude product was used without purification for a Schotten–Baumann esterification with

• His-tagged enzyme was obtained through heterologous expression and purification by Ni2+-NTA affinity chromatography (Figure S1, Supporting Information File 1). After incubation of the purified enzyme with the 13C-labelled SNAC derivatives (S)-11 or (R)-11 for 30 minutes at 25 °C, the incubation buffer

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• limitations, such as possible Cα epimerization [45] during SNAC coupling and essential HPLC purification, which was generally difficult and time-consuming. Developing other different methods, exceptionally more straightforward approaches to access activated substrates, would solve this inevitable bottleneck

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• desired product, which proved to be unstable during purification (Scheme 4). Homopropargylic azides containing electron-rich nitrogen heterocycles could not be obtained. No product was observed by using vinylindole 1d probably due its high tendency to polymerize. Although a slight amount of

• % yield of the azido-arylated product, and using the more nucleophilic 13 only slightly improved the yield. Finally, a small amount of product resulting from the addition of allyl-BF3K 14 could be observed but decomposed during purification. Based on literature precedence [41][42][44] and experimental

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• % conversion when 1 equivalent of sulfinate was used. Products 8 exhibited instability in the presence of water, leading to the formation of hydrolysis product 9 [25] in the reaction mixture. This instability caused issues during the reaction work-up, and attempts for purification using column chromatography

• 12a, diazide 13, and hydrolysis product 9 [25] which were inseparable using common purification methods (Table 1). The pivotal advancement occurred when attempting the reaction in DMSO (Table 1). In the case of 8a (R = 4-CH3C6H4), the product precipitated out when full conversion was reached

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

• Corp., TCI, Sigma-Aldrich) and used as received without further purification. Li+@C60TFSI− was purchased as PF6− salt from Idea International Corp., and then its counter anion was exchanged to TFSI− according to reported procedures [9]. NMR spectra were recorded on a JEOL JNM-ECZ400S (1H: 400 MHz, 7Li

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• ][21][22]. Multicomponent reactions (MCRs) provide one-pot reactions, simple synthetic procedures, less waste being produced, fewer purification steps, and a high atom economy [23]. The GBB three-component reaction is carried out in the presence of Lewis or Brønsted acid catalysis to increase the

• furnished good results for the HPW-catalyzed GBB-3CR with yields greater than 63% (5m–o). It is always important to point out the limitations of a given method and in our case, we did have some. Purification by column chromatography became necessary since product isolation by precipitation was not effective

• . The catalyst was impregnated in the isolated crude product, and its removal through a recrystallization step was not successful. The use of a liquid–liquid extraction work-up step proved less effective compared to column chromatography purification. Moreover, attempts to recover the catalyst were not

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• yield an ethanol extract. This extract was further processed with ethyl acetate (EtOAc) three times. The combined EtOAc phase was then dried using a rotary evaporator to obtain the EtOAc extract, which was stored at −80 °C until further purification process. The above fermentation broth was adsorbed

• EtOAc extracts were dried using a rotary evaporator to obtain the final EtOAc extract, which was stored at −80 °C until further isolation process. Compounds purification The EtOAc extract (3.5 g) obtained from the fermentation broth of XISR I medium underwent column chromatography on silica using a

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

• Cloning, expression, and purification Streptomyces leeuwenhoekii NRRL B-24963 [28] was used as a template to amplify the hyg17 (GenBank CQR59633) with the primers 5’-GTTAGCCATATGACGGTCGCCGTCGTGGGC-3’ and 5’-GTAATGCTCGAGCGGCGCCACCGGCACCGA-3’. hyg17 was cloned into pTip-QC1 [10] using NdeI and XhoI

• /off cycles for 5 min at a duty cycle of 50). Initial purification was performed with gravity filtration using nickel-nitrilotriacetic acid (Ni-NTA) resin (GE Healthcare). Cell lysate was loaded onto the Ni-NTA resin and washed with binding buffer. Protein was eluted using increasing concentrations of

• NaCl, 20 mM Tris pH 7.5) for another 10 min. Then MgSO4 (to ≈1 mM) and 0.2 mg DNase (Thermo Fisher Scientific) were added and stirred for 10 min. The lysate was centrifuged to remove debris for 45 min at 10,000 rpm and 4 °C, and the lysate was collected into a beaker. Purification was then performed

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• (SORHA), Triticum aestivum (TRZAS), and Zea mays (ZEAMX). LpFAT A expression and purification: The fat a03 gene from Lemna paucicostata, in which the N-terminal amino acids representing the chloroplast transit peptide were replaced by an N-terminal 6xHis-tag, was cloned into a pET24 vector [3]. The LpFAT

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• compound producers. Among the rare actinomycetes, Saccharopolyspora sp. KR21-0001 isolated from soil on Ōha Island, Okinawa, Japan was selected as a potential producer. The strain was cultured in 20 L of production medium in a jar fermenter and the culture broth was extracted. Further purification revealed

• minute) for 7 days. Purification and extraction The 7-day culture broth of Saccharopolyspora sp. KR21-0001 was centrifuged at 3000 rpm for 10 min. The supernatant fraction was eluted stepwise with 1.5 L of MeOH/H2O (0%, 50%, and 100%) through a HP20 column (55 i.d. × 500 mm), and all fractions were

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• sesquiterpenoids (1, 2), together with three known related analogs (3–5) [10][11][12][13] have been isolated and identified from the bioactive fraction of P. boydii CS-793. Details of the isolation and purification, structure elucidation, and biological evaluation of compounds 1–5 are described herein. Results and

• Discussion For chemical investigation, the solvent EtOAc was used to extract the fermentation culture of the fungus P. boydii CS-793 to afford an organic extract. Isolation and purification of the crude extract with a combination of column chromatography (CC) by Lobar LiChroprep RP-18, silica gel, Sephadex

• chromatography (TLC) was performed with precoated Si gel GF254 plates (Merck, Darmstadt, Germany). Solvents used for extraction and purification were distilled prior to use. Peptone from yeast extract was purchased from Sigma-Aldrich. Rice, monosodium glutamate, and corn steep liquor were purchased from China

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• Supporting Information File 1). To isolate the main difluorinated product 3a, the reaction vessel was purged with nitrogen and the product mixture was partitioned between water and DCM to remove HF and salt by-products. Purification of 3a by column chromatography gave 3a as a white crystalline solid in 65

• . Again, purification by column chromatography gave the products 3 as white crystalline solids and the structures of compounds 3f and 3i were confirmed by X-ray crystallography (Figure 2 and Supporting Information File 1). Molecules 3a, f, and i all exist in the solid state with the dicarbonyl moiety

• difluorinated product 5a in 85% isolated yield. Purification of 5a was achieved very readily by eluting the reaction mixture through a small quantity of silica gel with chloroform and evaporating the residual solvent to leave the crude product which could be further purified by recrystallization. Subsequently

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• of PdCl(C3H5)(dppb) (30.5 mg, 0.05 mmol) at 150 °C during 16 h in DMA (4 mL) under argon affords the coupling products 1–18 after evaporation of the solvent and purification on silica gel. Eluent EtOAc/heptane 1:9 for compounds 3–8, 10–18; heptane for compounds 1, 2, and 9. General procedure for the

• DMA (4 mL) under argon affords the coupling products 19–27 after evaporation of the solvent and purification on silica gel. Eluent EtOAc/heptane 1:9 for compounds 19–24; heptane for compounds 25 and 26; EtOAc/heptane 2:8 for compound 27. General procedure for the palladium-catalyzed synthesis of 9

• (4 mL) under argon affords the coupling products 28–30 after evaporation of the solvent and purification on silica gel. Eluent EtOAc/heptane 1:9 for all compounds. Structure of fluoranthene. Pd-catalyzed access to fluoranthenes. Scope of the Pd-catalyzed direct arylation reaction of arenes with 1,8

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• . Results and Discussion We found that a convenient way toward 6,8-di-tert-butyl-2-(arylamino)-3H-phenoxazin-3-ones 4 involves the short-term heating (30 min) of a molten mixture of 1 and an arylamine at 250 °C, followed by purification of the products by column chromatography. No preliminary grinding of

• potential for testing as potential donors for organic solar cells or as dye sensitizers for dye-sensitized solar cells [24][25]. Experimental All reagents and solvents were purchased from commercial sources (Aldrich) and used without additional purification. The compounds were characterized by 1H, 13C, and