Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

• of the PMB group on the tetrazole ring for each compound. For 11, a correlation of tetrazole Cq (δC = 150.4 ppm) with the benzylic protons of the PMB group (δH = 5.66 ppm, see Supporting Information File 1, Figure S3), was observable. Similar analysis for 12 indicated no such correlation. In order to

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

• give the tetralin product. Instead, we only isolated 30% yield of the difuranyl-substituted compound 15 as the major product. In addition, aldehydes 13e or 13f bearing a methyl group at the acetaldehyde side or the benzylic position of the alkene side were also suitable substrates for this cascade

• strategy: the 1,2,4-trisubsitituted tetralins 14ea and 14eb as well as the 2,4,4-trisubsitituted tetralins 14fa and 14fb were obtained in moderate to reasonable yields. The aldehyde 13g bearing a phenyl group at the benzylic position of the alkene side was also tried. Under the standard conditions, the

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• -amino ketone derivative 124 in high yield and diastereoselectivity (Scheme 34). A reduction of 124 gave a mixture of diastereomeric alcohols, and the one with (R)-configuration at the benzylic position was isolated in 54% yield. Further treatment of the alcohol with NaH furnished a cyclized product

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• % yield and <5% ee. The poor enantiomeric excess of the product 23 indicates that the racemization takes place during the course of the reaction. It was explained that the reason for the loss of optical purity was due to the formation of a benzylic cation, which is stabilized by the electron-rich aromatic

• enantioselectivity varied with the polarity of the solvent. The optimization study disclosed that the enantioselectivity increases with the decrease of the polarity of the solvent (Scheme 68). Yu and co-workers reported a novel segment-coupling Prins cyclization involving sequential benzylic/allylic C–H bond

• DDQ and the subsequent abstraction of hydride from the benzylic or allylic position generated a charge-transfer complex 298. The complex 298 formed a tin-containing ate oxocarbenium ion complex 299 with SnBr4, and then rapid C–C bond formation took place to generate the cyclic intermediate 300. The

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• radical C(sp3)−H halogenation at the benzylic and allylic position using N-halosuccinimide with azobisisobutyronitrile or benzoyl peroxide as a radical initiator is known as the Wohl–Ziegler bromination reaction, which requires heating, acidic/basic conditions, and/or UV irradiation (Scheme 1a) [17][18

• reported the manganese-porphyrin-catalyzed chlorination and bromination of C(sp3)−H bonds, respectively (Scheme 1d). Groves et al. also reported the manganese-salen-catalyzed fluorination of benzylic C(sp3)−H bonds [49]. Although these methods are efficient, they have a limited substrate scope

• (cycloalkanes and substrates bearing a benzylic C–H group). Therefore, there remains room for the development of a simple manganese catalytic system to achieve C(sp3)−H halogenation using commercially available reagents. Herein, we report a manganese-catalyzed C(sp3)–H bromination reaction at the methine and

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• )chloromethane via a published protocol for radical chlorination of an acetal due to the presence of vulnerable benzylic methyl groups proximate to the acetal [10]. We then synthesized carboxylic acid 9, from which we anticipated creating an aryloxylchlorofluoromethane (10, X = Cl, Scheme 4) via

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• that could react with olefin 120 with an electron-withdrawing group to give alkylation product 121 under irradiation with light (Scheme 41). The reaction is compatible with various substrates, including alkenes, secondary alkylpyridinium ions, benzylic pyridinium ions, and primary alkylpyridinium ions

Amino- and polyaminophthalazin-1(2H)-ones: synthesis, coordination properties, and biological activity

• Zbigniew Malinowski,
• Emilia Fornal,
• Agata Sumara,
• Renata Kontek,
• Karol Bukowski,
• Beata Pasternak,
• Dariusz Sroczyński,
• Joachim Kusz,
• Magdalena Małecka and
• Monika Nowak

Beilstein J. Org. Chem. 2021, 17, 558–568, doi:10.3762/bjoc.17.50

• 2-chloro-N,N-dimethylethylamine and 4-(2-chloroethyl)morpholine and further palladium-catalyzed amination of lactams 3 with aliphatic, aromatic, benzylic, cyclic amines and polyamines. Furthermore, we have demonstrated that some of the phthalazinone derivatives act as ligands and form stable

A new and efficient methodology for olefin epoxidation catalyzed by supported cobalt nanoparticles

• Lucía Rossi-Fernández,
• Viviana Dorn and
• Gabriel Radivoy

Beilstein J. Org. Chem. 2021, 17, 519–526, doi:10.3762/bjoc.17.46

• benzylic alcohol byproducts (Table 1, entries 6–9). In view of these results, we decided to continue the optimization of the reaction conditions by testing other oxidizing agents and solvents but only for the CoNPs/MgO catalyst. Thus, we found that using this catalyst, in refluxing MeCN as the solvent and

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• very poor stabilizing power by π-electron donation. A trend exists in the magnitude of the parameter according to the nature of the carbenium ions, which is in line with the carbenium ion stability (alkyl < allylic < benzylic). Thus, an increased π-electron transfer is present in the least-stabilized

• observed predominantly at the benzylic position (Δδ13C = 110.1 ppm), with minor impacts at the ortho- and para-positions (Δδ13C ≈ 20 ppm) relative to the starting alcohol 9c [37]. These variations are fully consistent with the presence of a positive charge located at the benzylic position, with only

•  5) [38]. Tidwell et al. explored the influence of a CF3 group on the solvolysis reaction of various benzylic sulfonate derivatives [39][40]. They found a linear free-energy relationship between the solvolysis rate of sulfonate 13f in different solvents compared to the one of 2-adamantyl tosylate

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• regioselectivity of transesterifications of hydroxylated alkyl and/or aryl moieties are sparser [26][34][35][36]. The extent to which Lipozyme® TL IM catalyzes feruloyl transfer reactions involving substituted benzylic alcohols was thus investigated to establish its usefulness for the preparation of both various

• polyhydroxylated molecules of interest (e.g., antioxidants) [4][26] and of novel chromogenic feruloylated substrates with various physicochemical features for screening applications. Accordingly, we observed that transesterifications only occurred when using primary benzylic alcohols; no phenol acylation was

• ], 4NTC–linker–Fe (12) is almost certainly a better analogue of ferulate linkages found in plant-based structures. Conclusion The use of immobilized Lipozyme® TL IM provides the means to perform the regioselective transesterification of the vinyl ferulate 2 to the primary hydroxy group of benzylic

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• regioisomers were assigned by chemical shifts of the singlet of the methoxy group. The products having the MeO and NO2 groups in the adjacent position have the signal of the methoxy protons shifted to a lower field. The assignment of the exo/endo-isomers was carried out by the position of the benzylic proton

Benzothiazolium salts as reagents for the deoxygenative perfluoroalkylthiolation of alcohols

• Armin Ariamajd,
• Nils J. Gerwien,
• Benjamin Schwabe,
• Stefan Dix and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2021, 17, 83–88, doi:10.3762/bjoc.17.8

• substitution reactions of this type are synthetically appealing as they avoid pre-generation of an active electrophile such as an alkyl halide. A selection of benzylic alcohols 2 was reacted under the standard conditions with BT-SC2F5 (1.25 equiv) and NEt(iPr)2 (2 equiv) in MeCN at −40 °C, providing the

• generated as a significant side product. Finally, the suitability of this methodology for the preparation of (heptafluoropropyl) thioethers was investigated by reacting a selection of benzylic alcohols 2 with BT-SC3F7. As for the pentafluoroethylthiolation reactions, efficient conversion was observed with

An atom-economical addition of methyl azaarenes with aromatic aldehydes via benzylic C(sp³)–H bond functionalization under solvent- and catalyst-free conditions

• Divya Rohini Yennamaneni,
• Vasu Amrutham,
• Krishna Sai Gajula,
• Rammurthy Banothu,
• Murali Boosa and
• Narender Nama

Beilstein J. Org. Chem. 2020, 16, 3093–3103, doi:10.3762/bjoc.16.259

• 19, Kamala Nehru Nagar, Ghaziabad, UP-201002, India 10.3762/bjoc.16.259 Abstract A convenient practical approach for the synthesis of 2-(pyridin-2-yl)ethanols by direct benzylic addition of azaarenes and aldehydes under catalyst- and solvent-free conditions is reported. This reaction is metal-free

• azaarene derivatives under neat conditions through a highly atom-economical pathway. To evaluate the preparative potential of this process, gram-scale reactions were performed up to a 10 g scale. Keywords: aldehydes; azaarenes; benzylic addition; green chemistry; solvent-free conditions; Introduction

• malononitrile under catalyst-free conditions have been reported [29]. Wang et al. reported the functionalization of benzylic C–H bonds of 2-methylazaarenes by nucleophilic addition to aromatic aldehydes catalyzed by acetic acid using harmful chlorinated solvent, and this reaction suffers from longer reaction

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• , entry 9). With the optimal conditions in hand, the reaction was exemplified with various other electrophiles (Scheme 2). The reaction gave generally good results with reactive electrophiles such as benzylic, allylic or propargylic ones (3a–k). Noteworthy, in the reaction with 2-(bromomethyl)pyridine (2g

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• ’ “Suman”, which means “Sunflower”), a beautifully simple yet much effective bowl-shaped C3-symmetric polycyclic aromatic hydrocarbon having three benzylic positions clipped between three phenyl rings in the triphenylene framework has attracted a tremendous attention of researchers worldwide. Therefore

• mixture of compounds. In sharp contrast, their attempt under flash vacuum pyrolysis (FVP) at high temperature was also fruitless may be due to the presence of three benzylic sp3 carbons which are unable to endure such harsh reaction conditions. Therefore, next they converted compound 6 into 1,5,9

• Z-oct-4-ene in toluene was found to be a more effective alkene source for the ring-opening reaction in comparison to the gaseous ethylene, as it increases solubility and also improve the lifetime of the catalyst. 2.1 Derivatization at benzylic position As can be inferred from the architecture of

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• visible-light-inactive molecules using PSCats 3.1 Benzylic C–H fluorination A seminal paper in the field of transition-metal-free direct C–H fluorination comes from Chen and co-workers, who applied aryl ketones as PSCats [135]. They discovered that the choice of the PS impacted the selective formation of

• mono- vs difluorinated products at the benzylic position; 9-fluorenone affords benzylic monofluorination and xanthone affords benzylic difluorination (Scheme 5). Importantly, this metal-free direct C–H fluorination proceeded without the need for any specialized photochemical equipment; under visible

• -light irradiation by a household (19 W) compact fluorescent light (CFL) bulb (emitting variable wavelengths in the range of ≈365–625 nm) [195] and under mild conditions. Control reactions revealed that both the PS and light were essential for the reaction to occur. According to their report, benzylic C

Selective preparation of tetrasubstituted fluoroalkenes by fluorine-directed oxetane ring-opening reactions

• Clément Q. Fontenelle,
• Thibault Thierry,
• Romain Laporte,
• Emmanuel Pfund and
• Thierry Lequeux

Beilstein J. Org. Chem. 2020, 16, 1936–1946, doi:10.3762/bjoc.16.160

• equiv) in dichloromethane. The reaction was slow and required heating (50–65 °C) for 26 h to reach a 75% conversion and afforded a mixture of E/Z-1a in 60% yield. However, a low E/Z selectivity (40:60) was observed (Table 1, entry 1). When using neat benzylic alcohol, completion was achieved after 20 h

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• . Noteworthy, the C2–N4 bond length does not change much along the IRC for the formation of 10; however, it is shortened more rapidly to give 11. The presence of partial double bond between C2–C(Ph) (benzylic position) allows electron delocalization around the reacting center, which results in stabilization of

• the transition state and so lowering the activation energy barrier (Figure 3a). On the other hand, stabilization of the benzylic cation is not possible along the IRC path for TS1′ (Figure 3b), since the bond distance C2–C(Ph) is found as around 1.50 Å showing a single bond character. This can be the

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• of the ortho-bromine substituent was again accomplished by metalation using TMPMgCl·LiCl and subsequent reaction with 1,2-dibromotetrachloroethane to afford 11 in 76% yield. A second bromination at the benzylic position provided the dibrominated derivative 12 in 66% yield. The substitution reaction

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• correlations from the exchangeable proton to C4a and C3 supported this linkage as well as hydroxylation at the benzylic position. Finally, the chemical shift of C8a at 137.4 ppm was in favor of N-substitution, and comparison with the literature values from 4-methoxy-1,3-dimethyl-2(1H)-quinolone (6, δ 138.4

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• in the presence of Ba(OH)2 to give the corresponding thietane-3-ols 145. In this reaction H2S first was deprotonated to the hydrogensulfide anion (−SH) by Ba(OH)2. The obtained anion nucleophilically attacked the less steric or benzylic ring carbon atom of the oxirane ring, giving mercaptoalkanolates

Distinctive reactivity of N-benzylidene-[1,1'-biphenyl]-2-amines under photoredox conditions

• Shrikant D. Tambe,
• Kwan Hong Min,
• Naeem Iqbal and
• Eun Jin Cho

Beilstein J. Org. Chem. 2020, 16, 1335–1342, doi:10.3762/bjoc.16.114

• derivatives (Scheme 2). First, the C–C cross-coupling process with Cy2NMe was explored, with variations of the benzylidene moiety. The reactions with both electron-donating (2b–2e) and electron-withdrawing substituents (2i–2m) proceeded well. Several functional groups, such as benzylic ones (2b and 2c