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

• . Based on our previous findings [17][18][19], the initial nucleophilic addition of α-aminoacetals 2a,b as nitrogen source to the activated heterodiene system of 4-methoxycarbonyl-DDs 1a–f in dichloromethane (DCM) or ethanol (EtOH) at room temperature affords N-aminohydrazone derivatives I (Scheme 2

• goal, different Lewis acids (10 mol %) such as Zn(OTf)2, CuCl2, and FeCl3 were screened at room temperature in different solvents, employing compound 4a as the model substrate (Table 1). From the set of data collected, both the formation of N,O-aminal 5a and corresponding hemiaminal 6a were observed

• dissolved in DCM (10 mL), FeCl3 (30 mol %) added and magnetically stirred at room temperature. Within 2–30 h, the reactions went to completion (TLC monitoring), affording, at last, N,O-aminals 5a–r (42–82%) and the corresponding hemiaminals 6a–p (4–35%) after column chromatography (Scheme 3). An increased

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

• represented below (Scheme 2) [34]. Morken and coworkers [36] set forth an intramolecular Lewis acid-mediated Cannizzaro reaction of aryl glyoxals 7 at room temperature using appropriate chromium or copper catalysts. The strategy afforded moderate to good yields of Mandelic esters 8 in the presence of Cr(ClO4

• proceeded with modest to good yields, in the range of 40–82%, and depicts the Cannizzaro reaction in the transfer hydrogenation process [35]. A facile room temperature Cannizzaro reaction protocol was established by Abaee et al. employing magnesium bromide etherate and triethylamine in dichloromethane [77

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• solvent as the best conditions (Table 2, entry 1). As shown above, the commercially available Grignard reagent 4a gave the corresponding homo-coupled product 3a in a short reaction time at room temperature. Subsequently, for the purpose of expanding the scope of substrates, we examined the in situ

• ]. Conclusion In conclusion, we have developed a novel Rh-catalyzed one-pot Ullmann-type homo-coupling reaction of Grignard reagents. The use of commercially available Grignard reagents gave the corresponding homo-coupling products even when carried out at room temperature and short reaction time. However

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• easily undergoes Cope rearrangement at 90 °C to generate the stereospecific 6/6-bicyclic product 10 in 96% yield (Figure 3A) [10]. This Cope rearrangement product was found as two inseparable atropisomers (10a/10b) at room temperature, which coalesced into a single conformer at 130 °C [10]. We

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

• what some previous studies have reported, hydrophobic packing did not accelerate the reaction and there was no transformation in the reaction within 10 h at room temperature [99][100][101][102][103][104][105][106]. This result suggests that it would be difficult to carry out the relevant IMDAF

• developed in this study, isolated double bonds in the fatty acid chains in sunflower oil do not undergo a side ene reaction with maleic anhydride, which requires high temperatures and/or metal catalysts, since the IMDAF reaction can be performed at 50 ºC or room temperature (Scheme 2) [125][126]. The olefin

• reaction, the acylation is followed by an intramolecular Diels–Alder reaction and the amide intermediate (a sample compound has been previously isolated and fully characterized as a result of detailed studies) is in equilibrium with the final product at room temperature in polar solvents such as DMSO

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• extraction, the square Cu-nanobrackets 1b were successfully obtained by the reaction between the nanobracket 4b and copper(II) acetylacetonate in THF at room temperature. The product was characterized as 1b by MALDI-TOF mass spectrometry (Figure 1a), absorption (Figure 1b) and Raman (Figure 2c

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• was achieved via anion exchange using LiNTf2. The synthesized TAAILs with the NTf2 anion are all ionic liquids with a melting point well below 100 °C and the majority of these ILs can also be described as room temperature ionic liquids (RTIL), with a melting point below room temperature. The short

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• radical ions of polyazahelicenes. The moderate fluorescence quantum yield of 48% (in MeCN) [46] implies that a non-emissive triplet-excited state (at room temperature) could also be generated via intersystem crossing, potentially initiating electron transfer reaction sequences. 77 K emission measurements

• chloride. We believe that our findings pave the way for a broader usage of the inherently chiral polyazahelicene photocatalyst class, both in photoredox and energy transfer catalysis. A) Room-temperature absorption (black) and emission (yellow) spectra of Aza-H recorded in MeCN/H2O (9:1), and fluorescence

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• -acetamide carboxamide oxindole hybrids 5 was obtained in moderate yields (26–63%), at room temperature, in short time (2 hours), proving the efficiency and the generality of this methodology. Aliphatic (2a, 2c and 2m), aromatic (2d, 2f, 2g, 2k and 2l), heterocyclic (2e, 2h, 2i, 2n and 2o), alkyne 2b and

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

• with Bi(OTf)3 (10 mol %) in acetonitrile at room temperature (Table 1, entry 1). The desired product was obtained in 72% after 12 h. When the reaction was carried out at 40 °C for 8 h, the yield increased slightly to 76% (Table 1, entry 2). When the reaction was carried out at 60 °C, the yield

• optimized conditions for substrates 9dc,dl, we found that in addition to the products of interest, they also formed the decarboxylated products as inseparable mixtures. Given this result, we investigated milder conditions to avoid decarboxylation. In doing so, we reacted the substrate 9dc for 24 h at room

• temperature. Despite this long reaction time, we still observed formation of the decarboxylated derivative, and we could also partly recover the starting material (Table 2). Decarboxylation reactions of indanones have previously been described in the literature. In 2008, Itoh et al. investigated the Nazarov

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

• temperature [41]. The coupling of several aromatic amines with aliphatic and benzylic alcohols was studied with bis-NHC-manganese complex (Mn6). A catalyst loading of 1.5 mol % in the presence of t-BuOK (1 equiv) at room temperature produced the corresponding N-alkylated amines with 40–93% yield (Scheme 11

• mechanism suggested that dearomatization–aromatization pathways operated for the dehydrogenation of the alcohol and C–C bond formations. After the successful attempt of bidentate N-heterocyclic carbene-manganese complex-catalyzed N-alkylation of amines with alcohols at room temperature [41], Liu and Ke's

• toluene at 135 °C for 18 h) (Scheme 55). The mechanistic investigation discussed the formation of a manganese imido complex by treating Mn9 with 1 equiv of t-BuOK at room temperature (rt) for 1 h in C6D6. The signal at 91.02 ppm in the 31P NMR spectrum confirmed the formation of the imido compound. C

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