Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• -oxo-2-phenylethyl)benzonitriles substituted with various groups (Br, Cl and methyl) on both the benzene rings were treated with different anilines to yield respective products (5a–m) in good yields (Scheme 3). Examination of the effect of the substituents on the reaction revealed that the substituents

• on both the benzene rings of 2-(2-oxo-2-phenylethyl)benzonitriles have no significant impact on the yields of the reaction delivering the corresponding products in almost similar yields (3b–e, Scheme 3). Interestingly, different alkylamines such as methylamine, ethylamine and piperazines were also

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• chiral N-arylbenzimidazoles involving a carbon–carbon bond cleavage under optimal reaction conditions. In the presence of CPA 2, N1-(aryl)benzene-1,2-diamines 66 were used in the reaction with multicarbonyl compounds 67 and 68 and afforded the corresponding products, axially chiral N-arylbenzimidazoles

• 69 and 70 in high yields (up to 89%) with excellent enantioselectivity (up to 98% ee, Scheme 22) [78]. The primary amino group in the N1-(aryl)benzene-1,2-diamines reacts with the carbonyl group in 67 to give imine intermediate I-15 mediated by the chiral phosphoric acid. Meanwhile, isomerization of

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• , cyclocondensation of 47 with 2-mercaptoacetaldehyde diethyl acetal (3nb) in the presence of p-TSA in benzene solvent afforded 1,3-oxathiolane intermediate (±)-2,2-bis(acetoxymethyl)-5-ethoxy-1,3-thioxalane (48). More recently, an approach developed by Snead et al. [53] at the Medicines for All Institute used lactic

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• radical cyclizations [22], Pschorr reactions [23], and diverse cycloaddition protocols [24][25]. Especially transition-metal-catalyzed cross-coupling reactions starting from benzophenones, benzoic acids, dihalogenated benzene building blocks and others have emerged as new approaches in recent years [26

AlBr₃-Promoted stereoselective anti-hydroarylation of the acetylene bond in 3-arylpropynenitriles by electron-rich arenes: synthesis of 3,3-diarylpropenenitriles

• Yelizaveta Gorbunova,
• Dmitry S. Ryabukhin and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2663–2667, doi:10.3762/bjoc.17.180

• , benzene and its polymethylated derivatives) under the action of aluminum bromide (AlBr3, 6 equiv) at room temperature for 0.5–2 h result in the stereoselective formation of 3,3-diarylpropenenitriles (Ar(Ar′)C=CHCN) in yields of 20–64%, as products of mainly anti-hydroarylation of the acetylene bond. The

• -3,3-diarylpropenenitriles 2a–o as products of the regioselective hydroarylation of the acetylene bond (Scheme 1). These reactions proceeded only with an excess of AlBr3 (6 equiv). Thus, running the reaction of nitrile 1a with benzene under the action of less amount AlBr3 (1–4 equiv) resulted in an

• NOESY correlations between the vinyl proton and the aromatic protons or methyl groups in neighboring aryl substituents (see Supporting Information File 1). However, the configuration of nitrile 2o was unclear. Benzene, o-, m-, p-xylenes, and 1,2,4-trimethylbenzene (mesitylene) were included in the

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• )benzene (7b). Hexanal (6b) reacted successfully with 4-fluoro-β-nitrostyrene (7c) and gave product 8d under all conditions tested (in solution, solvent-free, and ball-milling conditions, vide infra). Again, small amounts of catalyst (S,R)-C2 gave the best chemical yield. Catalyst (S,R)-C2 (3 mol %) in

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• Lewis acid concentration, or by the decrease of temperature. The use of TMSN3 enabled a more efficient exclusion of water from the reaction mixture in comparison to a HN3 solution in benzene, which is difficult to dry thoroughly. This, in turn, was helpful in shifting the Schmidt reaction towards

• for the preparation of tetrazoles with hydrazoic acid Caution: Hydrazoic acid should be handled with care in an efficient fume hood since it is toxic and explosive. In a two-neck round-bottom flask equipped with an addition funnel and argon inlet, a benzene solution of hydrazoic acid (18 mL) and boron

• trifluoride etherate (1.15 mL) were placed. The mixture was cooled with an ice water bath, and a benzene solution of the carbonyl compound (1.50 mmol in 15 mL of benzene) was added dropwise over 40 minutes with stirring and cooling. After the addition was completed, the reaction mixture was left at room

Efficient synthesis of polyfunctionalized carbazoles and pyrrolo[3,4-c]carbazoles via domino Diels–Alder reaction

• Ren-Jie Fang,
• Chen Yan,
• Jing Sun,
• Ying Han and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2021, 17, 2425–2432, doi:10.3762/bjoc.17.159

• crystal structure of compound 4g was determined by X-ray diffraction (Figure 4). It can be seen that the ring of pyrrolo[3,4-c]carbazole exists in a slightly twisted plane. The dihedral angles of the phenyl and the benzoyl group to the central benzene ring are 72.018° and 88.402°. To further expand the

• with benzylideneacetone gave the desired carbazoles 6m and 6n albeit in significantly lower yields. Thus, this one-pot domino reaction successfully constructed carbazoles with four substituents on the benzene ring from the corresponding indole derivatives with two molecules of chalcones. It should be

Synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and their transformations under superelectrophilic activation conditions

• Andrey I. Puzanov,
• Dmitry S. Ryabukhin,
• Anna S. Zalivatskaya,
• Dmitriy N. Zakusilo,
• Darya S. Mikson,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2021, 17, 2417–2424, doi:10.3762/bjoc.17.158

• ), oxadiazole 3a gave the product of hydration of the acetylene bond (4d, yield of 65%) existing in solution as equilibrium between ketone and enol forms in a ratio of 1.2:1 according to NMR data (see Supporting Information File 1). Then, reactions of 5-acetylenyl-1,2,4-oxadiazole 3a–d with arenes (benzene and

• proton and aromatic protons (see Supporting Information File 1). In the case of the reaction with o-xylene, pairs of E/Z-isomers of two regioisomers, (E/Z)-5b and (E/Z)-5b1, were obtained. We also checked the reaction of oxadiazole 3a with benzene under the action of Lewis acids AlCl3, AlBr3 and acidic

• in the same reaction in TfOH (compare entry 3 in Table 2 with data shown in Scheme 5). Thus, among the tested acidic reagents, TfOH showed better results for the hydroarylation of compounds 3. Additionally, the reaction of oxadiazole 3a with benzene in TfOH (rt, 1 h) in the presence of cyclohexane

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• isolated in 80% yield over two steps. Reduction of the ester provided allylic alcohol 29 (92%) ready for later epoxidation. After considerable optimizations, the authors found that the dropwise addition of TBHP to 29 in refluxing benzene solution containing a catalytic amount of VO(acac)2 afforded the

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• ), δC 170.0.0 (C-7), and δC 169.4 (C-10). The downfield methine proton signals at δH 6.96 (d, J = 8.7, 1.8 Hz, H-2), 7.52 (td, J = 8.7, 7.2, 1.8 Hz, H-3), 6.94 (td, J = 8.7, 1.8 Hz, H-4), and δH 7.99 (dd, J = 8.1, 1.8 Hz, H-5) were consistent with a 1,2-disubstituted aromatic benzene ring of a salicylic

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• proceeding by means of the initial generation of an iminyl radical that cyclizes onto the electron-rich aromatic ring or through the formation of a radical cation on the electron-rich benzene ring. Finally, the methodology has successfully been applied to synthesizing the natural product trisphaeridine

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• (Table 1) of compound 1 displayed characteristic resonances for a 1,3,4-trisubstituted benzene ring [δH 7.00 (d, J = 1.9 Hz, H-2), 6.87 (dd, J = 8.1, 1.9 Hz, H-6), and 6.78 (d, J = 8.1 Hz, H-5)], a 1,3,4,5-tetrasubsituted benzene ring [δH 6.62 (brs, H-2′) and 6.65 (brs, H-6′)], an oxygenated methine [δH

• (Table 1) showed a 1,3,4-trisubstituted benzene ring [δH 6.58 (d, J = 2.3 Hz, H-2), 6.57 (d, J = 8.0 Hz, H-5), and 6.49 (dd, J = 8.0, 2.3 Hz, H-6); δC 146.9 (C-3), 143.9 (C-4), 131.9 (C-1), 121.2 (C-6), 114.2 (C-5), and 112.2 (C-2)], a 1,3,4,5-tetrasubstituted benzene ring [δH 6.73 (s, H-2′, 6′); δC

A novel methodology for the efficient synthesis of 3-monohalooxindoles by acidolysis of 3-phosphate-substituted oxindoles with haloid acids

• Li Liu,
• Yue Li,
• Tiao Huang,
• Dulin Kong and
• Mingshu Wu

Beilstein J. Org. Chem. 2021, 17, 2321–2328, doi:10.3762/bjoc.17.150

• -withdrawing motifs, and thus gave a better result. For example, the (2-oxoindolin-3-yl) phosphate substrates with a methyl or methoxy group at the 5-position of the benzene ring could all react with hydrobromic acid in good yield, giving 4b, 4c, and 4g in 72–76% yield. The position of the residue R1 on the

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• substituted diaryl ketone, 4-(4-methoxybenzoyl)benzonitrile (96) serves as the HAT photocatalyst to activate the C(sp3)–H bonds for olefin functionalization. It was identified that the use of nonpolar, aprotic solvents, such as benzene and α,α,α-trifluorotoluene (TFT) is critical for the formation of the

Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account

• Ranadeep Talukdar

Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137

• benzene which resulted in low yields of the products 134 (Scheme 18a) [44]. Using different N-protected substituted indoles 135, Naidu observed improved yields of 136 when catalytic oxidant I2 was added in 1,4-dioxane as solvent (Scheme 18b) [96]. Using aerial oxygen as the oxidant, Yang used Se0 in the

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• active (Table 1, entry 6). With the identification of cyclopropenimine 5 as our optimal catalyst [44], we examined the effect of the reaction medium. Solvents such as benzene (Table 1, entry 7), TBME (Table 1, entry 8), and toluene (Table 1, entry 10) produced reactivities on par with ethyl acetate and

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• three linearly fused benzene rings. Because of their extended aromatic and conjugated π-system, anthracene derivatives possess interesting photochemical and photophysical properties [1][2][3], as well as gelling ability [4]. These important properties make them relevant for the development and

• sequential modifications [30], photocyclization of divinylterphenyl derivatives [31], tandem radical cyclization of (Z,Z)-1,4-bis(2-iodostyryl)benzene derivatives [32], and ring-closing olefin metathesis of tetravinylterphenyls [33] as the best-known synthetic routes. Herein, we have classified the synthetic

• with internal alkynes 11 bearing an electron-donating or electron-withdrawing group on the benzene ring resulted in the corresponding substituted anthracenes 12 in moderate to good yields (see the representative examples 12a–g). The same authors also investigated the applicability of reacting internal

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• biologically active molecules (22 and 23) (Scheme 9A) [92]. Interestingly, the same conditions could be used for benzene hydroxylation to obtain phenol but were ineffective with benzene rings bearing either electron-donating or electron-withdrawing substituents. Notably, the catalyst could be reused five times

• reaction suggested it goes through a radical pathway. Similar to the oxidation of alkanes to give alcohols and carbonyl compounds, vanadium complexes have been reported to mediate the hydroxylation of arenes, including the obtaining of phenol from benzene. However, most mechanistic studies provided

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• room temperature within 0.1 h for a successful reaction. The salt 5-4v was so powerful that it fluorinated an equimolar amount of benzene in dichloromethane in 2 h at 40 °C. In general, triflate salts were more effective than BF4 salts because of the higher solubility of the triflate salts in a

• reactivity than the sulfonamide reagents such as Barnette’s N-fluoro-N-alkylarenesulfonamides, since the electronic density on the nitrogen was greatly decreased by two strong electron-withdrawing CF3SO2 groups. Reagent 7-1a reacted slowly with benzene and toluene under neat conditions, whereas activated

• fluorination of benzene and anisole under excess substrate conditions gave fluorobenzene and fluoroanisoles in 88% and 98% yield, respectively. The reaction with sodium diethyl phenylmalonate gave the fluorinated product in 93% yield (Scheme 26). 1-12. N-Fluorolactams A new class of N-F fluorinating agents, N

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

• Suraj Patel,
• Tyson N. Dais,
• Paul G. Plieger and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

• ]metaparacyclophane and a cyclohexadienone cyclophane. Keywords: cyclophane; metaparacyclophane; nitration; paracyclophane; rearrangement; Introduction Cyclophanes have been described as having bent and battered benzene rings [1] due to a structure that involves one, or more, aromatic rings linked by aliphatic

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• , the reactions with other 2-(2-vinylphenyl)ethanals 13b–g carrying different substituents on the benzene ring or on the side chain with veratrole and furan as the nucleophiles were investigated. As can be seen from Scheme 7, under comparable conditions, most reactions proceeded smoothly with the

• in 38–72% yield. To our gladness, aldehyde 13d, with an electron-deficient nitro group residing on the benzene ring reacted with veratrole under the standard conditions, delivering tetralin 14da in 55% yield. However, using furan as the nucleophile component, the reaction sequence with 13d failed to

• )acetaldehydes or 3-(2-vinylphenyl)propanal by action with BF3 to generate benzyl carbenium ions that are captured by a Friedel–Crafts alkylation reaction with a range of electron-rich benzenes or heteroaromatics. The method has a relatively broad applicability allowing variation in the benzene ring as well as

Co-crystallization of an organic solid and a tetraaryladamantane at room temperature

• Fabian Rami,
• Jan Nowak,
• Felix Krupp,
• Wolfgang Frey and
• Clemens Richert

Beilstein J. Org. Chem. 2021, 17, 1476–1480, doi:10.3762/bjoc.17.103

• by crystallization at room temperature, using dichloromethane as solvent. Results We opted for a benzene derivative for our first foray into organic solids to be encapsulated in TAA crystals, because a number of benzene derivatives have been found in EnOCs in the past [13][14][15]. Phenol was

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• anhydro nucleoside 26 and its transformation into the aminonucleoside 27. The key intermediate nucleoside 27 was then treated with 3-ethoxypropenoyl isocyanate or 3-methoxy-2-methylpropenoyl isocyanate in a mixture of benzene and DMF, followed by acidification with sulfuric acid affording the nucleosides

• and treatment with pyrrolidine in acetonitrile to afford the C-3’-aminonucleoside 58. The reaction of this key intermediate with 3-ethoxypropenoyl isocyanate or 3-methoxy-2-methylpropenoyl isocyanate in a solvent mixture of benzene and DMF, followed by acidification with sulfuric acid produced the

• solution mixture of benzene and DMF, followed by acidification with sulfuric acid produced nucleosides 63 and 64, respectively (Scheme 14) [47]. 1,4-Furanosyl double-headed nucleosides A literature search revealed two different categories of 1,4-furanosyl double-headed nucleosides. In the first category

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• be considered as a 1,3,5‐triphenylbenzene derivative enjoying with three methylene units clipped in such a manner that all the four benzene rings are in conjugation with coplanar arrangement, resulting strong π–π stacking in addition to the strong electron‐donating ability which in turns provide a

• corresponding desired truxene-based oxazole derivatives (Scheme 6). Additionally, to enhance the conjugation which in turn would undoubtedly tune the properties of the truxene-based heterocyclic systems, we also design and synthesized the benzene-bridged oxazole derivative 25 in three steps (Scheme 7). As can

• . 320.41 nm and 291.07 nm in addition to an extra band at 263.22 nm due to the fusion of three benzene rings onto the imidazole moieties. In sharp contrast, more red-shifted absorption bands at 341.64 nm and 326.99 nm along with two shoulders at ca. 306.75 nm, and 279.94 nm were found with truxene having