Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• , supramolecular chemotherapy has received considerable attention by utilizing a supramolecular strategy to decrease the cytotoxicity of anticancer drugs to normal cells while preserving their cytotoxicity against cancer cells [11]. Supramolecular systems derived from macrocycles [12][13], such as calix[n]arenes

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• containers. The emphasis is on those reactions that give different product distributions on the potential reactive sites inside the containers than they do outside, free in solution. Specific cases include site-selective cycloaddition and addition of arenes, reduction of epoxides, α,β-unsaturated aldehydes

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

• summarizing recent relevant literature reports. Keywords: annulation; cyclization; fused indoles; regioselectivity; SEAr; Introduction Over the decades, countless cyclization and annulation reactions of substituted arenes/heteroarenes involving an electrophilic aromatic substitution (SEAr) reaction as the

• or annulation of: (A) substituted arenes/heteroarenes and (B) 3,5-unsubstituted, 4-substituted indoles. Indole C3 regioselective intramolecular alkylation of indolyl allyl carbonates. Indole C3 regioselective Michael-type cyclization in the total synthesis of (−)-indolactam V. Synthesis of azepino

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

• macrocyclic cavity. Keywords: 1,2,3-alternate conformation; calix[6]arenes; gold(I) catalysis; phosphines; Introduction One of the latest challenges in supramolecular chemistry is the design and development of novel macrocyclic-based entities able to influence the catalytic activities of the metal center [1

• high symmetrical geometry. Finally, a single broad peak for the four methoxy groups ($) appears at 2.96 ppm. In analogy with parental diureido and dithioureido calix[6]arenes, we were able to observe the presence of a second minor cone conformer, in a ≈4:1 ratio, highlighted by the presence of a second

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

• are scarce and they have mostly been focused on the fluorinations of enolizable substrates. These considerations led us to explore the behavior of NFSI in fluorinations of activated arenes under ball-milling conditions towards an eventual implementation of mechanochemistry in late-stage C–H

• . Results and Discussion Previous reports in the absence of solvent have shown that NFSI promotes aromatic fluorination at temperatures between 80 °C and 105 °C [25]. To commence, we focused on the reaction between arenes 1a–c and NFSI by ball milling in the absence of external heating (Scheme 2a). To

• fluorination of arenes 1 with NFSI. (a) Product distributions and reaction conditions: Arenes 1 (0.148 mmol) were milled with NFSI (1.0–2.0 equiv) in a 2 mL Eppendorf tube with four ZrO2 milling balls (350 mg in total mass) at 25–30 Hz for 3 h. The yield of the products was determined by NMR analysis with 4

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• ruthenium complexes which are efficient as catalysts elevated the scope of this metal in synthetic organic chemistry. For clarity and ease of understanding of the topic, this review is categorized into four sections: cyanation of amines, cyanation of arenes and heteroarenes, photocatalyzed cyanation, and

• such as piperidine, tetrahydroisoquinoline derivatives, and pyrrolidine were also tolerated well in this reaction. The use of the non-toxic and inexpensive acetone cyanohydrin makes this method more advantageous compared to the known methods. 2 Cyanation of arenes and heteroarenes 2.1 Cyanation of

• arenes and heteroarenes using heterogeneous catalysts In 2012, a novel strategy for the 3-cyanation of indole in the presence of Ru(III)-exchanged NaY zeolite (RuY) was reported [36]. In this reaction K4[Fe(CN)6] was utilized as the cyano source in DMF at 110 °C. The Cu(OAc)2 and O2 (1 atm) was found

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

• initiated, the reaction will propagate, which typically involves the insertion of a π-system (carbometallation of alkenes/alkynes) in the case of organoiron species (Scheme 2). Alternatively, the generated radical species may undergo radical addition to alkenes, alkynes, or aromatic arenes. The final step

• examining of other potential arenes capable of undergoing electrophilic aromatic substitution would expand the applicability of the reaction. Carboazidation In 2018, Yang investigated the three-component carboazidation of styrene derivatives 115 with alkanes 101/139b and trimethylsilyl azide for the

• to the breadth of reactions viable from iminyl radicals, generating through the homolytic cleavage of the N–O bond, a number of Fe-catalyzed domino reactions have been investigated. In 2018, Okamoto and Ohe reported an iminoarylation of γ,δ-unsaturated oxime esters 165 with arenes 166 (Scheme 35

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• ][40] including from properly functionalized arenes and alkenes [41][42][43][44][45][46][47][48][49][50][51][52][53]. In the case of such substrates having oxygen-containing functional groups, PIFA attacked the double bond first [41][42][43]. With unsaturated amides or hydroxamates, oxidation of the

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

• desirable. In this sense, Tan and co-workers (2020) developed the first chiral phosphoric acid-catalyzed atroposelective C–H amination of arenes for the synthesis of N-arylcarbazole structures. The atroposelective N-arylcarbazoles 58 were prepared by C–H amination of azonaphthalene derivatives 54 and

• rearomatization-enabled central to axial chirality transfer pathway [73]. Citing the crucial role of di-carbazole-substituted arenes in OLED materials [74], Tan and co-workers have recently developed structural motifs with two chiral N-aryl axes from 2,6-diazonaphthalene 61 and carbazoles 62. For this reaction, a

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

• Systems of RAS, Liteyniy pr., 55, Saint Petersburg, 191014, Russia Department of Chemistry, Saint Petersburg State Forest Technical University, Institutsky per., 5, Saint Petersburg, 194021, Russia 10.3762/bjoc.17.180 Abstract Reactions of 3-arylpropynenitriles (ArC≡CCN) with electron-rich arenes (Ar′H

• ]. Recently, we have shown that reactions of 3-arylpropenenitriles (cinnamonitriles, ArCH=CHCN) with arenes (Ar′H) under the superelectrophilic activation by the Brønsted superacid CF3SO3H (TfOH, triflic acid) or the strong Lewis acid AlBr3 result in the formation of 3,3-diarylpropanenitriles (Ar(Ar′)CHCH2CN

• arenes under the action of the strong Lewis acids, aluminum halogenides AlX3 (X = Cl, Br) and the Brønsted superacid TfOH (CF3SO3H). Results and Discussion It was found that acetylene nitriles 1a–c reacted with arenes in the presence of excess AlBr3 (6 equiv) at room temperature for 0.5–2 h to afford E,Z

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• arenes (Scheme 13). In this transformation, the azide anion is oxidized to its radical, and this process requires a high reduction potential that cannot be achieved by iridium and ruthenium-based catalysts. In contrast, [Cu(dap)2]Cl and [Cu(dap)Cl2] were found suitable for the oxidation. Based on a

• with oxime esters. Oxo-azidation of vinyl arenes. Azidation/difunctionalization of vinyl arenes. Photoinitiated copper-catalyzed Sonogashira reaction. Alkyne functionalization reactions. Alkynylation of dihydroquinoxalin-2-ones with terminal alkynes. Decarboxylative alkynylation of redox-active esters

Direct C(sp³)–H allylation of 2-alkylpyridines with Morita–Baylis–Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement

• Siyu Wang,
• Lianyou Zheng,
• Shutao Wang,
• Shulin Ning,
• Zhuoqi Zhang and
• Jinbao Xiang

Beilstein J. Org. Chem. 2021, 17, 2505–2510, doi:10.3762/bjoc.17.167

• . However, these reactions were mainly suitable to strong nucleophiles such as malonates, amines, or alcohols etc. [20][21][22][23]. The allylic substitution reactions using some weak nucleophiles, such as alkyl aza-arenes, were very limited [24][25][26][27][28][29]. In 2014, Rios and coworkers developed a

• reported C(sp3)–H allylic substitution reactions were mainly applied on the 2-alkyl-azaarenes containing strong electron-withdrawing groups. While the reactions with inactive alkyl-aza-arenes were rare [30][31]. Kim et al. have reported a K2CO3-promoted one-pot allylation reaction of 2-alkylpyridines with

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• also reported the Co-catalyzed C–H alkoxylation of ferrocenes under nearly room temperature [38]. In comparison, despite the direct C–H amination of arenes with alkylamines has emerged as an efficient strategy to prepare substituted anilines [39][40][41][42][43][44][45][46][47][48][49], the application

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

• reaction of the acetylenyl-1,2,4-oxadiazoles with arenes in neat triflic acid TfOH (CF3SO3H) at room temperature for 1 h resulted in the formation of E/Z-5-(2,2-diarylethenyl)-3-aryl-1,2,4-oxadiazoles as products of regioselective hydroarylation of the acetylene bond. The addition of TfOH to the acetylene

• the transformations of these heterocyclic compounds in electrophilic media. The main goals of this work were the synthesis of 5-arylacetylenyl-1,2,4-oxadiazoles and the study of their reactions with/without arenes under the conditions of superelectrophilic activation by the Brønsted superacid CF3SO3H

• ), 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

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

• recently as precursors in Friedel–Crafts reactions of arenes [30][31] and cross-coupling reactions of arylboronic reagents [32]. However, the direct SN1 reaction of such isatin-derived 3-phosphate-substituted oxindoles by halide ions as nucleophiles has not been developed yet and remains an unsolved

Transition-metal-free intramolecular Friedel–Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives

• Tülay Yıldız,
• İrem Baştaş and
• Hatice Başpınar Küçük

Beilstein J. Org. Chem. 2021, 17, 2203–2208, doi:10.3762/bjoc.17.142

• arenes using the FCA methods with π-activated alcohols and organocatalysts has begun to be preferred over using conventional reagents, such as organohalogens and transition metal catalysts, which are toxic and require working under harsher conditions [38]. After these developments, the intramolecular FCA

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

• -deficient arenes [4][5][6][7]. Operating FC reactions in versatile synthons such as Morita–Baylis–Hillman (MBH) adducts is a challenging process. Inter/intramolecular Friedel–Crafts reactions of Morita–Baylis–Hillman adducts leads to a variety of products such as quinolinones [8], cycloheptene-6

• affect the scope of the reaction. On contradictory to the literature reports [Cr(III)salenCl] complex surprisingly catalysed the intramolecular Friedel–Crafts reaction in electron deactivated arenes of MBH adducts [10][11][12][13][14]. However, ortho/meta-substituted arenes of MBH adducts were inert to

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

• efficiently cyclized [42]. Friedel–Crafts alkylation of arenes with aromatic aldehydes The Lewis acid-catalyzed Friedel–Crafts alkylation of electron-rich arenes with aromatic aldehydes has proven an efficient and often direct method to prepare anthracene derivatives. Kodomari and co-workers disclosed a

• convenient synthesis of triarylmethanes and 9,10-diarylanthracenes from reactions of arenes and aromatic aldehydes by using acetyl bromide in the presence of silica gel-supported zinc bromide [43]. The methodology developed by these authors involved using excess of one of the reagents. When the authors

• derivatives. In this work, the reaction of phthalaldehyde (44) with arenes 45 resulted in anthracene derivatives 46–48 as major products (Scheme 10) [17]. In fact, the authors obtained mixtures of anthracene derivatives, with 9-arylanthracenes 47 in greater proportion in almost all reactions. On the other

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

• 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

• present in the natural product bismurrayafoline E (36) [105], an alkaloid found in the leaves of Murraya koeniggi (Scheme 13D) [106]. The oxidative formation of carbon–carbon bonds mediated by vanadium has been reported as a method for the aminomethylation of arenes and heteroarenes. The so far described

• were found to be unreactive, probably due to steric hindrance. The one-pot difunctionalization of arenes involving a sequential C–O cleavage and C(sp2)–H activation mediated by chromium was recently reported by Luo and Zeng [124]. The reaction allows an ortho-directed diarylation of o

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• remarkable robustness of the copper-promoted C−H activations with alkynes, we became interested to explore the working mode by a set of experiments. To this end, electron-poor arenes inherently reacted preferentially in intermolecular competition experiments (Scheme 4a). This observation could be explained

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

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

• (difluoromethoxy)arenes, while the reaction with dichlorocarbene gives salicylaldehydes via hydrolysis of an ortho-dichloromethylphenol: the Reimer–Tiemann reaction. The literature, other than this single reference with pentafluorophenol [6], is bereft of references to the capture of heterodihalocarbenes by phenol

• the corresponding mass was observed by GC–MS, we were unable to isolate 13 in pure form. The base-mediated method we have reported herein is complementary to that of Scheeren, since it is apparently more practical for electron-poor arenes, while the bis(aryloxy)chloromethanes required as intermediates

• in Scheeren’s method must be constructed with electron-rich arenes under highly acidic conditions. Furthermore, the method detailed in this work is operationally simple, not requiring the use or isolation of unstable intermediates and giving electron-poor bis(aryloxy)fluoromethanes in a single step

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

• with electron-rich as well as electron-poor arenes and heteroarenes. Subsequently, in order to prove the practicability of this approach, 1,2,3-triazoles were assembled by reaction of 157 with alkynes. In 2019, Bosque and Bach [41] reported that 3-acetoxyquinuclidine (q-OAc) could be utilized as an

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• central aromatic ring (Ar1) (Scheme 3, route b). The teraryl structures were constructed by the formation of two C–C bonds via tandem Suzuki–Miyaura coupling of two terminal (Ar2) and central (Ar1) arenes. It is noted that dihalogenated arenes were adopted as components for the central aromatic ring (Ar1

• ) in the teraryl structure, because the diborylated arenes were less available. Either (a) the coupling of boronic acid esters bearing one acetal moiety with dihalogenated arenes or (b) the coupling of dihalogenated arenes bearing two acetal moieties with arylboronic acids were conducted for the

• , and heterohelicenes. Results and Discussion Carbohelicenes such as [5]helicene (1a) and [6]helicene (1b) were synthesized via Suzuki–Miyaura coupling of readily available dihalogenated arenes 2 with phenylboronic acid ester 3 bearing a (1,3-dioxolan-2-yl)methyl group [29], followed by triflic acid