Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• aryl residue allowed the monofunctionalization to occur selectively. Also, amide 1g bearing a disubstituted arene was successfully functionalized in 59% yield. Finally, the difunctionalized thiophene derivative 2h was obtained in 56% yield. In 2016, Wang's group developed another methodology for the

• trifluoromethylthiolation of azacalix[1]arene[3]pyridines by C–H bond activation using a complex of Cu(ClO4)2·6H2O and the shelf-stable Me4NSCF3 [115][116] as a nucleophilic source of SCF3 (Scheme 3) [100]. Within these conditions, a set of six azacalix[1]arene[3]pyridines bearing electron-donating groups, halogens or

• (25d) or withdrawing group (25e) and the desired SCF3-containing products were obtained in moderate to good yields. The functionalization of trisubstituted arene 25g and heteroarene 25h was also possible leading to the corresponding products 26g and 26h in moderate yields (23% and 42% yields

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• loses dihydrogen to give a neutral borane 12, followed by B–C(sp2)/B–H transborylation with HBpin (ΔG‡ = 14.7 kcal mol−1) to give the borylated arene 13 and regenerate the catalyst (Scheme 4a). Fontaine showed that the steric bulk of the Lewis base had a significant effect on the rate of the reaction

• (Scheme 16) [75]. The reaction was proposed to occur through activation of the alkyl fluoride 68 with H-B-9-BBN, followed by electrophilic substitution of the arene 69 to give a Wheland intermediate and a fluoroborohydride 70 (Scheme 16). Loss of H2 gave the arylated product 71, dihydrogen, and F-B-9-BBN

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

• nucleophilic arenes under oxidative acidic conditions.The synthesis of CDIS is more challenging since the arene moiety must be covalently connected to the iodoarene prior to cyclization. Recently, we published two new methods that describe the generation of carbon- and heteroatom-bridged CDIS [28][29]. Herein

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• showcasing innovative research regarding supramolecular catalysis using macrocyclic and acyclic hosts, as well as other molecular architectures such as self-assembled capsules and metallocages. In their contribution, Secchi and Cera [15] reported the synthesis of diphosphine gold(I) calix[6]arene complexes

• whose geometry, in low-polarity solvents, is controlled by the 1,2,3-alternate conformation of the calix[6]arene skeleton. These catalysts can tune the selectivity of the catalytic cycloisomerization of 1,6-enynes in response to the relative orientation of the coordinated gold(I) atom with respect to

• -workers [19] reported an efficient photocatalytic supramolecular system based on a self-assembled nanosystem. The self-assembled system was obtained in an aqueous medium by inclusion of ammonium benzoyl-ʟ-alaninate (G) in a tetraphenylethylene-embedded pillar[5]arene (m-TPEWP5). The resulting worm-like

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

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

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• readily available 3(2H)-isoquinolones followed by TfOH-promoted hydroarylation by an arene molecule. Screening of the novel 1,2,4-trisubstituted 1,4-DHIQs against cancer cell lines confirmed high cytotoxicity of selected analogs, which validates this new chemotype for further investigations as anticancer

• ) transformation resulted in the highly diastereoselective formation of C-arylation products 10 which in some cases was accompanied by a regioisomer formation (with respect to the entering arene moiety) and the formation of 3-isoquinolones 15 (isolated and characterized in several instances). Not unexpectedly

• of compound 9a, by single-crystal X-ray analysis. A curious and somewhat unexpected result was obtained when trying to employ N-formyl-N-methylaniline as an arene in the TfOH-promoted arylation of 10a. Instead of the anticipated product 9aa, 73% yield of predominantly trans-configured formate ester

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• decades. With the combination of C–H activation, many aminations of aryl compounds have been established [6][7][8][9][10][11][12][13][14][15][16]. However, it is necessary to introduce the directing group into the arene in most successful cases. As a good amino source, phthalimides have been widely

• -layer chromatography (TLC) on gel F254 plates. Flash column chromatograph was carried out using 300–400 mesh silica gel at medium pressure. General procedure for synthesis of 3a–u: N-Hydroxyphthalimide (0.1 mmol), CuBr (40 mol %, 0.04 mmol), triethyl phosphite (6.0 equiv, 0.6 mmol) and (hetero)arene (2

Tetraphenylethylene-embedded pillar[5]arene-based orthogonal self-assembly for efficient photocatalysis in water

• Zhihang Bai,
• Krishnasamy Velmurugan,
• Xueqi Tian,
• Minzan Zuo,
• Kaiya Wang and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2022, 18, 429–437, doi:10.3762/bjoc.18.45

• supramolecular self-assembled nanosystem based on host–guest interactions between water-soluble tetraphenylethylene-embedded pillar[5]arene (m-TPEWP5) and ammonium benzoyl-ʟ-alaninate (G) in an aqueous medium. The obtained assembly of m-TPEWP5 and G showed aggregation-induced emission (AIE) via the blocking of

• photochemical catalytic reaction in aqueous medium. In addition, our group [30] reported the construction of a supramolecular photocatalytic system with a two-step FRET process through the supramolecular assembly of water-soluble pillar[5]arene and TPE derivatives as donor and EsY and Nile Red (NiR) as

• dehalogenation reaction with high yields within shorter reaction time is vastly essential and of industrial importance. Herein, we have fabricated a supramolecular AIE-emissive photocatalytic system (m-TPEWP5G–EsY) based on the host–guest interactions between meso-TPE embedded water-soluble pillar[5]arene (m

Borylated norbornadiene derivatives: Synthesis and application in Pd-catalyzed Suzuki–Miyaura coupling reactions

• Robin Schulte and
• Heiko Ihmels

Beilstein J. Org. Chem. 2022, 18, 368–373, doi:10.3762/bjoc.18.41

• ) to failed reactions (4d and 4g). In this context, the different reactivity of the methoxy-substituted arene isomers 4d–f and 4i is instructive as the para isomer did not result in product formation, whereas the ortho and meta-isomers gave reasonable yields. Hence, there is no obvious impact of the

• have a main impact on the reaction outcome as both examples of ortho- and para-substituted arene derivatives give similar yields. These results show that there is obviously a fine balance between stereoelectronic and steric effects that determines the outcome of the reaction, as has been shown for the

A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• Tommaso Lorenzetto Fabrizio Fabris Alessandro Scarso Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’ Foscari di Venezia, via Torino 155, 30172, Mestre-Venezia, Italy 10.3762/bjoc.18.38 Abstract The hexameric resorcin[4]arene capsule as a self-assembled organocatalyst promotes a

• compared to many other strong Brønsted or Lewis acids. Keywords: cationic intermediates; encapsulation; organocatalysis; resorcin[4]arene hexamer; supramolecular catalysis; Introduction In enzymatic catalysis, the substrate is selected matching the size, shape and specific functional groups present in

• [20] or hydrogen bonding units. In the latter case, a key role is played by the resorcin[4]arene 1 as a one-step multigram synthesis product, that spontaneously self-assembles in wet apolar solvents like chloroform or benzene forming a hexameric structure [21] thanks to the formation of a seam of

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• ring-closure step have been routinely employed for the construction of diverse arene- and heteroarene-fused rings (Scheme 1A) [1][2][3]. In most of these approaches, the new CAr–C bond is formed ortho to the tether/directing functionality on an aromatic or a heteroaromatic ring, as the geometrical

• regioselective cyclization of an indole-tethered donor–acceptor cyclopropane. Indole C5 regioselective epoxide–arene cyclization. Funding We acknowledge the financial supports received from DST-SERB, New Delhi (Grant No. CRG/2018/003021) and Council of Scientific and Industrial Research (CSIR), New Delhi (Grant

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• , calix[4]- [9][10][11][12][13] and resorcin[4]arene [14][15][16][17] are the most exploited cavitands due to their inherent limited flexibility and already proved their ability to control the catalytic activity of late-transition metals and particularly gold(I) catalysts [18][19][20][21][22][23][24][25

• ]. This occurs via strong steric interactions, often outside the macrocycle (Figure 1a) [11], that affect the first coordination sphere of the metal or by creating a spatial confinement around the metal that is thus directed towards the inner cavity (Figure 1b) [26][27]. Contrarily, calix[6]arene

• devised a new family of triphosphine calix[6]arene gold(I) complexes (Figure 1c) [30]. These cavitands are able to form (pseudo)rotaxane species, by threading viologen-based guests, with a conformational control operated by the sulfonamido hydrogen-bonding donor domain [31][32]. Furthermore, their

Multi-faceted reactivity of N-fluorobenzenesulfonimide (NFSI) under mechanochemical conditions: fluorination, fluorodemethylation, sulfonylation, and amidation reactions

• José G. Hernández,
• Karen J. Ardila-Fierro,
• Dajana Barišić and
• Hervé Geneste

Beilstein J. Org. Chem. 2022, 18, 182–189, doi:10.3762/bjoc.18.20

• milling (Figure 1b and Figure S5 in Supporting Information File 1). Other substrates such as naphthalene and N-Boc-aniline proved unreactive under the milling conditions with NFSI. However, the more activated arene 2-naphthol underwent double fluorination affording 1,1-difluoronaphthalen-2(1H)-one as the

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• ) [137]. The reaction most likely involves an iminyl radical which undergoes a 5-exo-trig cyclization with the alkene to form the alkyl radical intermediate. Homolytic aromatic substitution (HAS) with the arene will afford the final functionalized product. Interestingly, electron-poor, electron-rich, and

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

• groups were tolerated [7]. In 2020, Tan and co-workers disclosed the phosphoric acid-catalyzed atroposelective arene functionalization of nitrosonaphthalene with indoles to form atropisomeric indole-naphthalenes 39 and indole-anilines 40 by a nucleophilic aromatic substitution reaction [61] (Scheme 13

• + 2] formal cycloaddition and central-to-axial chirality conversion. Organocatalytic atroposelective arene functionalization of nitrosonaphthalene with indoles. Proposed reaction mechanism for the atroposelective arene functionalization of nitrosonaphthalenes. Asymmetric construction of axially chiral

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

• also less desirable as reaction intermediates, owing to the difference in their respective reactivity. The results for the route going through N-methyl-2-(aminomethyl)biphenyls 9 are summarized in Scheme 4. We found that substrates bearing electron-donating groups at the aminomethyl carrying arene (9b

• and 9d) afforded significantly lower yields (28 and 34%) than substrates with electron-donating substituents at the other arene (9a and 9c; 59–67%), which were in the same range as the model reaction with unsubstituted amine 2b. Next, reactions with primary 2-(aminomethyl)biphenyls were investigated

• counterpart starting from secondary amine 9b (34%), the trend of electron-donating groups at the aminomethyl carrying arene adversely affecting the yield was also observed for primary amines. The negligible difference in yields for fluorenone 10b starting from amine 15b1 (34%) and 15b2 (38%) respectively

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

• hydroarylation of nitriles 1. Reactions of nitriles 1a–c with o-xylene led to the formation of regioisomers derived from the electrophilic substitution at different positions of this arene. Thus, nitrile 1a gave two types of regioisomers 2n and 2o. After reactions of nitriles 1b,c with o-xylene, compounds 2l and

• AlBr3 to both the nitrile and acetylene bonds of the starting compound 1 furnishes the highly electrophilic species A bearing a positive charge on the acetylenic carbon atom C3. The subsequent reaction of species A with the arene molecule via electrophilic aromatic substitution results in the formation

• of species B. The most probably, this stage proceeds stereoselectively due to spatial factors, with the incoming arene Ar′H attacking the acetylene bond in an anti-position to the bulky AlBr3, that determines the final predominant formation of the mainly anti-hydroarylation products of the starting

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

• nucleophilic arene molecules, species B should afford substances 5 as products of hydroarylation of the acetylene bond of the starting compounds 3. Indeed, reaction of 5-acetylenyl-1,2,4-oxadiazoles 3a–c with excess of TfOH at room temperature for 1 h resulted in the quantitative preparation of E/Z-isomers of

Facile and innovative catalytic protocol for intramolecular Friedel–Crafts cyclization of Morita–Baylis–Hillman adducts: Synergistic combination of chiral (salen)chromium(III)/BF₃·OEt₂ catalysis

• Karthikeyan Soundararajan,
• Helen Ratna Monica Jeyarajan,
• Raju Subimol Kamarajapurathu and
• Karthik Krishna Kumar Ayyanoth

Beilstein J. Org. Chem. 2021, 17, 2186–2193, doi:10.3762/bjoc.17.140

• the Cr(salen)/BF3·OEt2 catalytic system (5m–r, Table 2). This could be an outcome of steric hindrance exerted by the substitutents at the arene moiety of the MBH adducts. Thereafter, to inspect the utility of the reaction for a gram-scale reaction, we endeavoured a model reaction using the optimized

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

• -diarylanthracene 43, so the authors concluded that triarylmethane is an intermediate in the reaction with excess benzaldehyde [43]. In 2009, Olah’s group applied BF3 monohydrate as acid catalyst in arene hydroxyalkylation with aromatic aldehydes, to provide triarylmethane, diarylmethylbenzaldehyde, and anthracene

• propargylic carbonates 113 with terminal alkynes 114. The scope of this reaction consisted of 12 examples that were synthesized in moderate to good yields (40–87%). The authors obtained the best yields by using electron-deficient aryl alkynes or secondary carbonates with electron-rich arene substituents (115a

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

• has been selectively feasible without activating a C(sp2)–H bond in the arene moiety. Verma and co-workers [91] have reported the use of VO(acac)2 immobilized over graphitic carbon nitride (VO@gC3N4) under visible light irradiation to perform a photocatalytic C–H activation of arene methides and

• evidence for radical pathways involving vanadium-peroxo species [76], with a few exceptions [95]. Vanadium-based catalysts have been employed in carbon–carbon bond formation reactions, such as arene couplings, thereby proving especially useful in the synthesis of bioactive compounds, including natural

• are crucial. In 2018, Ackermann and co-workers described a novel room temperature C–H arylation by using a continuous visible light photo-flow technique, allied with a manganese photocatalyst CpMn(CO)3 [142]. The new flow protocol enabled the synthesis of several arene- and heterocyclic-based

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• substituent at the arene ring produced predominantly symmetric THP product 26 over the desired trisubstituted heterocycle 23. The mechanism of the reaction was further investigated using enantioenriched homoallylic alcohol (S)-18 with 89% ee, which favored 2-oxonia-Cope rearrangement to give THP 23 only in 14

• activation via DDQ oxidation, followed by nucleophilic attack of an unactivated olefin to obtain all-cis-trisubstituted Prins products with high stereochemical precision [111]. A single-electron transfer (SET) mechanism was proposed for the above transformation (Scheme 69). A SET from an arene or alkene to

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

• – the classic Reimer–Tiemann intermediate. This was the case even after the addition of water and continued stirring to allow time for a hypothetical intermediate (bromofluoromethyl)arene to hydrolyze. A general procedure for the production of electron-poor bis(aryloxy)fluoromethanes is to stir

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

• electron-withdrawing groups, the scope of the reaction comprises anilines including electron-withdrawing or electron-donating substituents in the arene, except N-acetylated or ortho-halogenated anilines. In 2017, Chen and colleagues [21] reported a method that promoted the formation of an alkoxy radical

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• reported two types of thiacalix[4]arene-protected titanium–oxo clusters [37]. In that work, p-tert-butylthiacalix[4]arene (H4TC4A) was introduced to tetranuclear and hexanuclear clusters Ti4 and Ti6, respectively (Figure 12). The formed hybrid materials had band gaps of 2.19 eV (Ti4) and 2.24 eV (Ti6). The

• titanium–thiacalix[4]arene-based clusters for H2 evolution, and it also provides a useful method for tuning the band gaps of the catalysts. Apart from reducing the distance between the electron donor and acceptor, calixarenes can also promote the charge separation to enhance the electron transfer [38

• ]. Zhou and co-workers employed 4-methoxycalix[7]arene and quartz beads as the host and packing material, respectively (Figure 13). The formed packed bed could then immobilize TiO2. Therein, the 4-methoxycalix[7]arene not only led to a decrease in the band gap of TiO2 but also prohibited the recombination