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

• conditions by utilizing a 7000-fold excess of dimethyl acetylenedicarboxylate (DMAD) at room temperature. The reactions were monitored by UV–vis spectroscopy. Compound 2 undergoes rapid reaction with DMAD under these conditions and is more than 90% consumed after 2.5 hours (Figure 8, top). Conversely

• -dicarboxylate (26) In a similar manner to [15], 1,3-diphenylisobenozfuran (2, 0.10 g, 0.37 mmol), 5 mL CH2Cl2 and dimethyl acetylenedicarboxylate (DMAD, 0.116 g, 0.814 mmol) were added to a round bottom flask. The reaction mixture was stirred at room temperature for 2 hours. The solvent was removed by rotary

• 1,4-dimesityl-1,4-dihydro-1,4-epoxynaphthalene-2,3-dicarboxylate (27) To a round bottom flask was added 1,3-dimesitylisobenozfuran (3, 0.05 g, 0.14 mmol), 5 mL CH2Cl2 and dimethyl acetylenedicarboxylate (DMAD, 2.31 g, 16.3 mmol). The reaction mixture was stirred at room temperature for 4 hours. 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

• /Et3N, followed by silica gel column chromatography, led to the triethylammonium salt of 2-N-Boc-aminoethylphosphinic acid 5 in 50 % yield. Alkylation of acid 5 with methyl chloroacetate in the presence of TMSCl and Et3N took five days at room temperature, and compound 6 as triethylammonium salt was

• 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

• the linear amide 11 was performed in DCM using a 10-fold excess of trifluoroacetic acid at room temperature, providing 1,4-azaphosphinine 12 in 68% yield. Various conditions used for the coupling of nucleobase 8, such as using silylated derivatives (HMDS, BSA) or salts obtained by base treatment (NaH

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

• ), H2SO4 (96 wt %, 3.00 g, 30 mmol, 2.5 equiv), I2 (0.04 g, 0.16 mmol, 0.01 equiv), and CH2Cl2 (1.50 mL) were inserted. The flask, kept under stirring at room temperature (rt), was light-shielded with aluminium foil and a water-cooled condenser was installed on its top. A solution of NaBr (2.88 g, 28 mmol

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

• . Cyclization of the latter under the action of K2CO3 in MeCN at room temperature gave previously unknown ethyl isoxazolo[4,5-b]pyridine-3-carboxylates 4a–c (Scheme 2). To the best of our knowledge only one compound (ethyl 5,7-dimethylisoxazolo[4,5-b]pyridine-3-carboxylate) has been synthesized using a similar

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

• equiv) of KOH in a 1:1 THF/H2O mixture to improve the solubility of the corresponding DCPQs (Scheme 4) at room temperature. A small amount of 1,4-dioxane (THF/H2O/1,4-dioxane 4:5:1) was also added to improve the solubility of 3a. The solution was rendered neutral by the addition of conc. HCl until

• , 2.56 mmol) and CH2Cl2 (20 mL). To the suspension was added 5,10-dihydropyrazino[2,3-b]quinoxaline-2,3-dicarbonitrile (8, 0.300 g, 1.28 mmol) in small portions. The reaction was allowed to proceed overnight at room temperature, after which a pale orange reaction mixture was filtered, washed with copious

• ), and 1,4-dioxane (2 mL). The resulting orange suspension was heated at 110 °C for 48 hours. After completion, the tube was allowed to cool to room temperature and placed in a freezer overnight. Gold-colored crystals of 5a were collected by filtration and dried in vacuo (430 mg, 1.28 mmol, 74%). 1H NMR

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• productivity in arylation processes [45]. These aryl(TMP)iodonium(III) carboxylates are stable at room temperature and are available as amorphous solids that dissolve in specific solvents, such as chloroform, methanol, and dimethyl sulfoxide. The iodonium salt 7aa does not decompose even at 70 °C, and further

• comparatively shorter time at room temperature, yielding high yields of the corresponding aryl(TMP)iodonium(III) carboxylates. Our method is compatible with a wide range of electronically and sterically diverse (hetero)aryl iodine(III) compounds, as well as aliphatic and aromatic carboxylic acids with a diverse

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• constant. The spin concentration Nspin for each sample was calculated from the Curie constant. ESR measurements were performed using a conventional ESR X-band spectrometer (JEOL, JES-FA300) at room temperature, where ca 1 mg of samples vacuum-sealed in glass tubes were used. In order to prevent the skin

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• that kind of chemicals [74]. The reaction was cheap because it took place by irradiation with green light (5 W) in the presence of eosin Y as photocatalyst, under 70 bar of CO, in CH3CN at room temperature (Scheme 41). In 2018, Wu et al. published two papers about the functionalization of indoles. In

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• . Trimethylsilyl azide is considered as a safe replacement of metal azides. We started the solvent optimization with MeOH and H2O as solvent system at room temperature, however, it did not yield any product even after 3 days (Table 1, entry 1). The use of DMF to improve the solubility of the paraformaldehyde solid

• products 3a–j (Scheme 2) in moderate to good yields when the reactions were conducted in DCM at room temperature for 24 hours. Both aliphatic and aromatic substituents on the tetrazole ring of the oxo component were equally well tolerated. Aliphatic aldehydes with aliphatic and aromatic groups reacted

• ). This method is applicable to different amines, isocyanide and acid components including Ugi-4-component and Ugi-tetrazole reactions proving the desired products with low to moderate yields. The Ugi reactions were performed in MeOH at room temperature for 24 hours and without any further optimization

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• for the treatment of muscle spasticity from spinal cord injury and multiple sclerosis [16]. Among all the sulfonyl-protecting groups used in this work, the removal of the N-nosyl group required milder conditions [22]. Deprotection of N-nosylated 4dd and 4de with thiophenol and K2CO3 at room

• temperature gave the NH-unprotected γ-lactam 5a and the drug (R)-rolipram 5b in 79% and 97% yields, respectively, with excellent enantioselectivity. Hydrolysis of γ-lactam 5a in 6 N HCl aqueous solution at 100 °C for 10 hours then led to the formation of (R)-baclofen hydrochloride (6) in 76% yield (Scheme 6

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

• were obtained by slow evaporation of the solvent from a mixture of the compound in dichloromethane and heptane at room temperature (Figure 3). Crystal structure analysis revealed that 5a crystallizes in a base-centered monoclinic system with the P21/c space group. The structure is mostly planar, except

• mmol; 3 mL) was added and the emulsion was stirred for 10 min at room temperature. The corresponding arylacetylene (p-tolylacetylene, 2.20 mmol, 0.28 mL) was slowly added dropwise to the reaction mixture and stirred for 6 hours at room temperature. The reaction was monitored by TLC until the reaction

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• reaction parameters, the desired three-component N-alkenylation was found to proceed smoothly by reacting 3a with excess amounts of 1 (2 equiv) and 2a (5 equiv) in MeCN (0.2 M) at room temperature, affording the trans-difunctionalized product 4aa as a single regio- and stereoisomer in 77% yield (Table 1

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• hydrochlorination is operating within the rate of diffusion control (Figure 4). They also noted that the reaction was significantly slower at room temperature when compared to reactions carried out at 0 °C. However, reaction rates were exclusively reported at 0 and −45 °C, indicating an inverse temperature

• hydrochlorination products in acceptable yields but that trimethylchlorosilane (TMSCl) was generally the most useful reagent (Scheme 9). The reactions were typically conducted at room temperature, as elevated temperatures led to a decrease in yield, and lower temperatures were prohibited by the freezing temperature

• of water. Under slightly more forcing conditions (5 equivalents of TMSCl and 5 equivalents of water), even 1-hexene and cyclohexene reacted successfully at room temperature to afford the corresponding products 56 and 57. Interestingly, Δ9,10-octaline gave exclusively the trans-product 32. 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

• DMSO at room temperature for 10 min using anhydrous NaOAc as a base to afford the corresponding boronated porphyrin conjugates 18–20 in 80–87% yields. Exploring the reactivity of the p-fluorine atom similar nucleophilic substitution reactions of porphyrin 6 were carried out with 1,8-diamino-3,6

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• was searched to identify actinomycete strains capable of growing at high temperatures (45 °C). This screening identified 57 actinomycete strains capable of growing at 45 °C. Comparative analysis of metabolites produced by these 57 actinomycetes at room temperature or high temperature revealed that

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• kept at room temperature for one hour. The reaction mixtures were concentrated in vacuo, dissolved in acetone, and then injected into a GC–MS system, Zebron ZB-WAX (30 m × 0.25 mm ID × 0.25 µm, Phenomenex), using He as the gas source at a flow rate of 1.41 mL/min. The initial temperature (120 °C) was

• for 1 h with 10 mg/mL lysozyme. After 10% SDS was added to the tube, the mixture was incubated at room temperature, 60 °C, and then 0 °C, for 5 min durations. AcOK (5 M) and phenol/CHCl3/isoamyl alcohol (25:24:1) were then added, and the resulting solution was gently mixed by inversion and centrifuged

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• started our studies with the palladium-catalyzed MCR of ethyl diazoacetate (1a), 1,3-butadiene (2a), and 1-phenylpiperazine (3a) in the presence of 5 mol % Pd(OAc)2 and 10 mol % Xantphos as ligand. To our delight, after irradiation with blue LED light in dimethylformamide (DMF) for 12 h at room

• temperature (rt), the desired unsaturated ε-AA derivative 4a was obtained in 75% isolated yield (Table 1, entry 1). Isolation and NMR analysis demonstrated that this model reaction provided amino acid 4a with good E-selectivity and excellent regioselectivity (E/Z = 91:9, 1,4-/1,2-addition >20:1). Control

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

• technique [25]. As expected, both substrates 1 and 2 reacted with Li+@C60 at room temperature and exhibited HPLC signals assignable to the desirable monoadducts 5a and 5b (Figure 2). It is noteworthy that the reaction of 2 proceeded faster than that of 1, although 2 has a lower HOMO level than 1. This is

• , 861.08866. HOMO levels of unsaturated substrates and LUMO levels of fullerenes computed at the B3LYP/6-31G(d) level of theory. HPLC profiles of themal [2 + 2]reaction of Li+@C60 with substrate 1 (a) and 2 (b) in o-dichlorobenzene at room temperature. HPLC profiles of 5a (a) and 5b (b) before and after

• photoirradiation at room temperature. 1H-1H 2D-NOESY NMR spectrum (600 MHz, CD2Cl2) of 5a (a) and NOE correlations between two protons. The spectrum (700 MHz, CD2Cl2) of 5b is shown in (b). Cyclic voltammograms of 5a, 5b, and Li+@C60 TFSI− with the potentials relative to the ferrocene/ferrocenium (Fc/Fc

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• ) [7]. Isolation of polycavernoside E (1) In a manner analogous to [7], the collected cyanobacterium (340 g) was extracted with EtOH (0.5 L) for 10 days at room temperature (rt). The extract was filtered, and the residue was homogenized with a blender and re-extracted with EtOH (0.5 L) at room

• temperature for one day. The extract was filtered, and the combined filtrates were concentrated. The residue was partitioned between EtOAc (3 × 300 mL) and H2O (300 mL). The combined organic layers were concentrated, and the residue was partitioned between 90% aqueous MeOH (300 mL) and hexane (3 × 300 mL

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

• single report on the use of a heteropolyacid (phosphomolybdic acid) in the GBB reaction but for a limited number of examples (Scheme 1a) [50]. That caught our attention for being the only example so far of a room temperature GBB reaction carried out in less than an 18-hour period. However, at least in

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

• , the pellet was resuspended in 40 mL of sucrose solution (25% sucrose, 50 mM Tris pH 8) using continuous stirring. Then, 10 mg of lysozyme (Bio Basic) was added and stirred at room temperature for 10 min, followed by the addition of 80 mL deoxycholate solution (1% deoxycholate, 1% Triton X-100, 100 mM

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• the reaction in the presence of DIPEA proceeded selectively, albeit more slowly. By increasing the DIPEA loading to 50 mol %, the product 2a was isolated in 75% yield after incubation for 7 days at room temperature. The structure of the obtained spirobutenolide was confirmed by single crystal X-ray

• data. Further syntheses of spirobutenolides 2 were performed under the one-pot conditions: after completion of the first O–H insertion step, a base was added to the reaction mixture and kept at room temperature until completion of the cyclization step, controlled by TLC. The results of the syntheses

• cyclization step was more selective and the total yield of the desired product was higher. The 6-exo-tet cyclization of intermediate compounds 16 under the action of DBU in acetone at room temperature proceeded within a few minutes, which is much faster than in the case of compounds 14. This can be explained

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

• ). Whilst tetrabutylammonium borohydride [22] at room temperature did not lead to a conversion of the starting material 5 either, a trace amount of desired 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine 7b was formed at elevated temperature, accompanied by disulfide 18b as the main product (Table 1, entries 5 and

• (13b): To a stirred mixture of 6-bromopyridin-2-amine (8, 10.00 g, 56.88 mmol, 1.00 equiv), 2-fluorophenylboronic acid (9.52 g, 65.98 mmol, 1.16 equiv), and Na2CO3 (12.06 g, 113.8 mmol, 2.00 equiv) in a mixture of 1,4-dioxane (80 mL) and water (80 mL) at room temperature was added Pd(dppf)Cl2 (1.67 g

• , 2.28 mmol, 0.04 equiv), and the mixture was stirred at 80 °C for 3 h. Thereafter, the reaction mixture was cooled to room temperature, diluted with water, and extracted thoroughly with ethyl acetate. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• coordination-switchable tweezers for switching between two magnetic states that are stable at room temperature [44]. To increase the magnetic coupling between the metal center the group investigated the Mn(III)–salphen tweezers 14 that can coordinate in apical position to cyanide ions. The complexation of CN

• electrostatic repulsion between the doubly charged redox-active units. Thus, it can be concluded that, although the tweezers exhibit different conformations in neutral and oxidized states, at room temperature

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• % conversion after 24 h, estimated t1/2 = 96 h, kobs = 1.4 × 10−6 s−1). With 55 μL MeOH in DCM, the relative rates for each substrate are 3,850:50:1 with urea 1a > carbamate 1b > benzamide 1c. The analogous toluene sulfonamide substrate 1d did not react on measurable timescales at room temperature (no product

• have been masked by the high temperatures and long reaction times of early reports. For example, Widenhoefer engaged carbamates and amides in dioxane at temperatures >80 °C [12][13]. Later work showed that ureas could be engaged at room temperature when a NHC–gold catalyst system was used, outpacing