First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• ), was subjected to cyclopropanation according to a method described in the literature [13]. To a solution of adduct 4b in toluene, (diacetoxyiodo)benzene and tetrabutylammonium iodide were added, and the resulting mixture was stirred at room temperature for 14 h. Unexpectedly, from the reaction mixture

• conducted in the same way. Cyclization of adduct 4 Cyclization was conducted according to the literature [13]. To a solution of adduct 4f (593 mg, 1.67 mmol) in toluene (7 mL), were added (diacetoxyiodo)benzene (539 mg, 2.5 mmol) and tetrabutylammonium iodide (618 mg, 2.5 mmol), and the resultant mixture

Asymmetric tandem conjugate addition and reaction with carbocations on acylimidazole Michael acceptors

• Brigita Mudráková,
• Renata Marcia de Figueiredo,
• Jean-Marc Campagne and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 881–888, doi:10.3762/bjoc.19.65

• min. Subsequently, 1.2 M dimethylzinc reagent in toluene (0.31 mL, 0.38 mmol, 1.5 equiv) was added dropwise to the solution and the resulting mixture was also stirred for 10 min. The acylimidazole (0.25 mmol, 1.0 equiv) dissolved in anhydrous THF (0.5 mL) was added dropwise to the mixture. The

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• pyridine N-oxides 9 with nonactivated secondary (2°) alkyl bromides 10 required 5 mol % of the Pd(OAc)2dppf catalyst, Cs2CO3 (2.0 equiv) as base in toluene at 100 °C as shown in Scheme 3. Under these conditions, the reaction provided diverse 2-alkylpyridine derivatives 11 in moderate to good yields

• ). In 2015, a palladium-catalyzed cross dehydrogenative coupling of pyridine N-oxides with toluene for the regioselective arylation and benzylation of pyridine N-oxide was reported by Khan and co-workers [92] (Scheme 23). The authors have shown toluene 117 when used as benzyl and aryl source remained

• toluene 117 by sulfate radical anion. Coordination of intermediate 120 and 121 leads to complex 122 which undergoes reductive elimination to provide product 119. 2-Ethyl-substituted pyridine N-oxides may undergo a dual C–H activation due to the buttressing effect of the ethyl group to produce azafluorene

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• 70–95%). The presence of a base and the type of solvent seems to be an important factor for the reaction course. In toluene, ionic liquid or in refluxing ethanol without a base [16][19][20] or in the presence of weakly basic pyridine [17][18][21] (pKa = 5.23 in water, 3.4 in DMSO, 3.3 in DMF, and

• ). α-Bromophenylacetic acid amides (4a,b) were prepared from 2-bromo-2-phenylacetyl chloride [38] and the corresponding amine in DCM or toluene at reduced temperature (see Supporting Information File 1). Thiobenzamides and thiobenzanilides were prepared by magnesium chloride-catalyzed thiolysis of

Synthesis of substituted 8H-benzo[h]pyrano[2,3-f]quinazolin-8-ones via photochemical 6π-electrocyclization of pyrimidines containing an allomaltol fragment

• Constantine V. Milyutin,
• Andrey N. Komogortsev,
• Boris V. Lichitsky,
• Mikhail E. Minyaev and
• Valeriya G. Melekhina

Beilstein J. Org. Chem. 2023, 19, 778–788, doi:10.3762/bjoc.19.58

• of the photoproducts (Table 2). Based on the structure of compound 11a we assumed that it could be converted into a polyaromatic product using conventional synthetic methods. However, the use of different systems (TsOH/toluene, HCl/EtOH, DBU/EtOH, MeONa/MeOH) resulted only in the decomposition of the

• could be achieved by using suitable dehydrating agents (TsOH/toluene, Ac2O/MeCN, SOCl2/toluene, CDI/MeCN, POCl3/toluene). Gratifyingly, it was shown that the application of 1,1-carbonyldiimidazole (CDI) in acetonitrile allows to convert compound 11g into the polyaromatic product 12a in 94% yield (see

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• Pd(OAc)2 did not dissolve in toluene even with pyridine. As a substitute for TEMPO, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) was tried (Table 1, entries 9 and 10) [45]. Although the reactivity was improved compared with the TEMPO catalytic system in Table 1, entries 3–5, the DDQ catalytic system

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• benzo[b]naphtho[2,3-f]oxepine 66 with tetrabromothiophene-S,S-dioxide in toluene followed by oxidative aromatization in the presence of DDQ afforded tetrabrominated aromatics 67 in an 81% yield. Subsequently, fourfold Suzuki–Miyaura cross-coupling of polybrominated compound 67 was performed, affording

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