Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• the synthesis of intermediate stilbenes 61 by Wittig coupling. The authors elected to use a Pd2dba3/DPEphos (L4)/Cs2CO3 system (dba = dibenzylideneacetone; DPEphos = bis[(2-diphenylphosphino)phenyl] ether) in toluene after catalyst and ligand screening. Cyclisation of several substituted 2,2

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• refluxing toluene under argon atmosphere (Scheme 9) [21]. In addition, the intramolecular coupling reaction of diphenyl pyren-1-ylphosphonate (47) accomplished the synthesis of 3-phenoxybenzo[f]pyreno[1,10-cd][1,2]oxaphosphepine 3-oxide (48) in 35% yield in the presence of largely excessive amounts of AlCl3

• palladium-catalyzed intramolecular arylation of 3-(2-bromophenyl)propyl alkylphosphinates 61 approached the synthesis of 3,4,5-trihydrobenzo[c][1,2]oxaphosphepine 1-oxides 62 in moderate 39–45% yields in the presence of triethylamine in dry toluene at 100 °C [33]. When the substrates were extended to 5

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• (toluene, acetonitrile, DMSO-d6) at room temperature, or when these solutions were slightly heated, the compounds 5a,b,e dissociated to form APBTTs 1 (the solutions got violet color, characteristic of compounds 1) (Scheme 10). In the presence of water (including the atmospheric moisture), hydration

• conditions (Table 2) of the model reaction of APBTT 1a and benzylamine were optimized. The best yield of PBTA 7a was observed when acetonitrile was used as the solvent and heated at 85 °C for 3 h (entry 2, Table 2). Since the product 7a isolation procedure proceeded more conveniently in toluene (the product

• the proposed approach to PBTAs were not successful. In the reaction of APBTT 1a with diethylamine (1a/diethylamine ratio of 1:1; stirring in toluene at 90 °С for 2 h; at 113 °С for 2 h; at room temperature for 24 h) and cyclohexylamine (1a/cyclohexylamine ratio of 1:1 or 1:5; stirring in toluene at

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• starting material had proved to be the most reactive imine in batch, leading, in the presence of 5 mol % of [Ru3(CO)12] and 3 equivalents of triethoxyvinylsilane in toluene at 150 °C after 5 h, to the alkylated aldehyde 2a with 62% yield, after purification on silica gel (Scheme 2) [21][39]. The flow

• controlled by a back-pressure regulator (BPR) to keep a pressure of about 130 bar, i.e., at a pressure much higher than that which causes the solvent (toluene) to boil in the reaction temperature range (150–200 °C). This homemade, pulsed-flow setup was used for optimizing the protocol while saving on

• . Unfortunately, with this catalyst, repeatability problems were detected (yield fluctuation of approximately 20%) which could be assigned to the low solubility of this catalyst in toluene. In order to overcome these problems, we synthesized triruthenium carbonyl complexes with phosphine ligand(s), namely

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• surprise, the application of Rh2(OAc)4 did not lead to the desired product neither in dichloromethane nor in toluene (Table 1, entries 1 and 2). Switching the catalyst to copper(I) iodide in refluxing DCM, did not result in the formation of product 6a, as well (Table 1, entry 3). However, when CuI was used

• in boiling toluene, 42% of the diazo reagent 5 was converted to 6a after only 1 hour of stirring. Thus, to increase the conversion rate, the reaction time was prolonged up to 3.5 h. Indeed, after this time, complete conversion of the diazo reagent 5 was observed and cyclopropane 6a was isolated in 74

• cyclopropanation. Reaction conditions: alkene (0.15 mmol), diazo compound 5 (0.1 mmol), CuI (1 mol %), dry toluene, 111 °C, Ar atmosphere. aYields refer to isolated products; bdr ratio determined by 19F NMR spectroscopy. Scope of the cyclopropanation. Reaction conditions: alkene (0.15 mmol), diazo compound 5 (0.1

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• hydrazone. Energy (eV) of molecular orbitals has been calculated at the m062x/6-311+G(d,p)/SMD=toluene level of theory. Global electron density transfer (GEDT). Dashed black line indicates both TS. ELF analysis for the reaction of series b leading to a system 6-6. Black trace corresponds to IRC. Colored

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• protected α-propargylglucose 42a or mannose 42b in the presence of CuCl in a toluene/H2O (4:1) (Scheme 7). Further a fully deprotected mannosyl residue 42c was also introduced via "click reaction”, yielding the glycoporphyrin 43c. Moreover, this methodology can also be utilized to introduce various

• conjugates (99a–d, 103a,b) were utilized for the preparation of porphyrin-fullerene dyads 100a–d and 104a,b in 30–70% yield by the reaction with C60 and sarcosine in toluene under microwave conditions. The photophysical and computational studies of these ZnP-Tri-C60 conjugates revealed that the 1,2,3

• ) with azides 169a–c in the presence of CuI and DIPEA in toluene under microwave conditions. Further, three triazole-meso-porphyrins 171a–c were prepared using a slightly modified Adler–Longo procedure. Also, the corresponding zinc derivatives 172a–c of these free-base porphyrins were synthesized in

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• ). It also appeared that the RCM depended on the substrate core structure and the presence of a protected allylic alcohol prevented the cyclization to take place. Taking these observations into account, the tricyclic [5-8-5] ring system 45 was obtained using the HG-II catalyst in refluxing toluene

• toluene in the presence of G-II catalyst and provided tetracyclic compound 96 with 50% yield. In this case, the RCM involved a terminal diene and a disubstituted diene. Further oxidation of the secondary alcohol furnished naupliolide (97). 1.2 Enyne ring-closing metathesis The enyne ring-closing

• from 5 mol % to 10 mol % almost doubled the yield (respectively 38% and 60% yield), and no significant increase in the yield was found when using 20% of catalyst (62% yield). Thus, the use of 10 mol % of [Rh(CO)2Cl]2 catalyst in toluene at 110 °C and under CO atmosphere yielded the cyclized compound

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• . Ltd., and used without further purification. Commercially available anhydrous solvents (THF, DMF, benzene, toluene, MeOH, EtOH, and CH2Cl2 Spectrochem) were used in the reactions. Thin-layer chromatography (TLC) was performed using precoated aluminum plates purchased from E. Merck (silica gel 60 PF254

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• solvent but is not necessarily required in the subsequent steps. When the reaction was carried out in benzene, CH2Cl2 or dioxane, much lower yields of 28%, 31%, and 8%, respectively, were obtained (Table 2, entries 2–4). Toluene gave the best yield with 55% (Table 2, entry 5). Therefore, further

• optimization steps were performed with toluene. By running the reaction at room temperature and decreased reaction times (3 h), the yield decreased to 28% (Table 2, entry 6). On increasing the reaction temperature to 50 °C instead, the product was isolated in 31% yield (Table 2, entry 7). Longer reaction times

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• adduct with 18 that was readily separable from the target ketones. Following the optimization of reaction conditions, a change of solvent to THF was shown to be as equally effective as toluene (Table 1, entry 10). The ketones S-9, S-10, and S-11 were obtained in a ratio of 1:6.9:5.2, indicating a higher

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• ) and the dimethylacetal derived from chloroacetaldehyde 11 affords the dithiolane 12. This 1,3-dithiolane spontaneously rearranges to the 1,4-dithiane with an elimination of hydrochloric acid by refluxing in a mixture of water and toluene. This two-step procedure constitutes a scalable and simple

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• to be the optimal solvent, while other commonly used solvents such as toluene, dioxane, and ethanol gave inferior yields (Table 1, entries 2–4, 14–39%). Further screening of bases did not improve the outcome of the product, whereas 63% yield of 3aa was obtained when acetic acid was added into the

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• refluxing toluene was reported to proceed with retention of configuration to afford the β-epimer 6 [16]. Another nice application of this chemistry was recently reported by Oestreich and co-workers, who converted 3β-hydroxypregn-5-en-20-one into the corresponding 3-bromo derivative, which also occurred with

Two-step continuous-flow synthesis of 6-membered cyclic iodonium salts via anodic oxidation

• Julian Spils,
• Thomas Wirth and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2023, 19, 27–32, doi:10.3762/bjoc.19.2

• decomposition of the intermediary iodoarene. Here it was possible to perform the procedure with either benzene or toluene, leading to a moderate yield of 38% and 37%. We could not use derivatives with any other substituents with secondary benzyl acetates since those led only to inseparable product mixtures

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• [3.2.1]octane 67 was achieved by a radical cyclization using n-Bu3SnH in refluxing toluene. A sequence involving an ester reduction, Ley–Griffith oxidation and Seyferth–Gilbert homologation with Bestmann–Ohira reagent allowed to obtain the alkynyl bicylo[3.2.1]octane 69. On the other hand, the five

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

• Anastasia Vepreva,
• Alexander Yanovich,
• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• Discussion The initial attempt to involve DAS 1b in the Rh2(esp)2-catalyzed insertion reaction with 4-(tert-butyl)phenol was successful. The initial adduct 5b was not purified and was heated at 140 °C in toluene to give compound 6b in 47% yield over two steps (Scheme 2). No further optimization of the

• from the data collated in Table 1, to our delight, cyclizations of the phenoxide anion generated on the action of base (except for 2,6-lutidine) proceeded as 5-exo-trig (rather than 6-endo-trig) process and yielded spirocyclic compound 7a as a mixture of syn and anti diastereomers. DABCO in toluene at

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• reducing agent sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al®), which is a convenient alternative to LiAlH4 that exhibits high solubility in organic solvents and is also known to reduce amides [17]. When a solution of amide 5 in toluene was treated with an excess of Red-Al® at 0 °C, rapid gas

• compound has also been prepared in racemic form [25]. To supply the final two carbon atoms found in the halichonic acids, amine 4 was condensed with a solution of ethyl glyoxylate in toluene, giving imine 7 in 95% yield. We found that imine 7 could be purified by column chromatography on silica gel if the

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• -(tetrahydro-2H-pyran-2-yl)-1-deazapurine (18) Compound 17 (1.72 g, 5.23 mmol), copper(I) iodide (CuI, 99.52 mg, 0.52 mmol), 1,10-phenanthroline (188.35 mg, 1.05 mmol), caesium carbonate (Cs2CO3, 2.38 g, 7.32 mmol) and benzyl alcohol (BnOH, 1.13 g, 1.07 mL, 10.45 mmol) were suspended in 2.62 mL toluene (0.5 mL

• was purified via silica gel chromatography using 0 to 4% methanol in dichloromethane as gradient. Yield: 395 mg of a mixture containing the 2-nitro-compound 20 and 21 (for NMR spectra see Supporting Information File 1). TLC: (5% acetone in toluene): Rf 0.34 (compound 20), Rf 0.05 (compound 21

• alcohol (BnOH, 328.55 mg, 310 µL, 3.04 mmol) were suspended in 0.76 mL of toluene (0.5 mL per 1 mmol compound 17) and stirred for 4 hours at 110 °C under atmospheric conditions. After complete reaction (TLC reaction control), the suspension was allowed to cool to room temperature and the catalyst was

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• toluene and acetone (2:1), mixture of chlorobenzene and acetone (2:1), or a mixture of hexachloroacetone and acetone (7:1). Under the optimized conditions, the screening of various polyphenols showed that the yields of products were 70–95% when the mixture of toluene and acetone (2:1) was used as solvent

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• in Table 1. Firstly, reaction with DIBAL in toluene at 0.3 M concentration and at 50 °C gave after 24 h almost complete conversion of the starting material to a symmetrical compound 8 that according to MALDI–TOF MS has lost two DCB groups and not any benzyl group. The compound was analyzed with 1H

• formed from 8. When 7 was reacted with 1.5 M DIBAL in toluene at 60 °C for 24 hours an almost equal amount of 8 and 9 was present (Table 1, entry 3) and 27% of triol 9 together with 32% of 8 was isolated. A tetrol 10 was obtained upon even longer reaction of 7: If reacted with 0.1 M DIBAL in toluene for

• mixture was left to stir overnight, and the reaction was quenched by addition of MeOH (10 mL). The mixture was diluted with toluene, and the organic phase washed with H2SO4 (1 M, 20 mL), then brine (3 × 20 mL), dried (MgSO4), filtered, and concentrated. Column chromatography in a solvent gradient of

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• of 2-aminobenzyl alcohol (1a) with 1-phenylethanol (2a) as model reaction in the presence of various cyclometalated iridium complexes TC-1–TC-6 (Table 1). Encouragingly, employing TC-1 as the catalyst, toluene as the solvent and t-BuOK as the base at 100 °C, quinoline 3aa was obtained in 73% yield

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• contrast, THF, toluene, DMF, and DMSO were inefficient reaction solvents (entries 11–14). Thus, 1,2-DCE was the best solvent for the reaction in terms of the product yield of 8a (99%), while chloroform posed a concern of acid contamination. Examination of the optimum amount of reagents 2a and 6a toward 1a

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• = Et (2.4 equiv), toluene, 60 °C). Further optimization with the pivalate led to 20 in 82% yield and 68% ee (19 R2 = t-Bu (2 equiv), cyclopentyl methyl ether, 22 °C). To account for the best results observed with pivalate 18, Guinchard and coworkers proposed the transition-state shown in Scheme 5 [31

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• observed (Figure 2c), which is similar to that of NI-PTZ. For NI-Ph-PTZ, a structured fluorescence band was observed in the 400–600 nm range (Figure 2d), which is assigned to LE emission. In toluene, however, a broad emission band centered at 624 nm was observed, which we attribute to the CT emission (with

• the phenyl moiety as donor group). The emission maximum (624 nm) is blue-shifted as compared to that of NI-PTZ (731 nm in toluene), indicating that the CT state energy of NI-Ph-PTZ is higher than that of NI-PTZ [47]. Similar results were observed for NI-PhMe2-PTZ (Supporting Information File 1, Figure

• (468.0 mg, 1.209 mmol), phenothiazine (289.0 mg, 1.452 mmol), Pd(OAc)2 (49.2 mg, 0.219 mmol) and sodium tert-butoxide (760.0 mg, 7.908 mmol) were dissolved in dry toluene (22 mL). Then tri-tert-butylphosphine tetrafluoroborate (66.4 mg, 0.229 mmol) was added. The mixture was refluxed and stirred for 8 h