Synthesis and investigation on optical and electrochemical properties of 2,4-diaryl-9-chloro-5,6,7,8-tetrahydroacridines

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 2450–2461, doi:10.3762/bjoc.17.162

• 3,5-dibromoanthranilic acid (1) [61] with cyclohexanone in POCl3 through an adapted reported procedure [62] (Scheme 1). With precursor 2 in hand, we intended to expand the π-conjugation of the tetrahydroacridine core by adding diversely substituted aryl groups using the Suzuki–Miyaura cross-coupling

• reaction [63][64]. As a model reaction, we studied the coupling between 2,4-dibromo-9-chloro-5,6,7,8-tetrahydroacridine (2) and phenylboronic acid (3a). After a thorough optimization using Pd(PPh3)4 as catalyst, toluene as solvent, and K3PO4 as base, the desired bis-arylated product 4a was isolated in up

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

• –Miyaura cross-coupling reaction of a variety of halogenated methoxybenzene-containing compounds with 2-(formylphenyl)boronic acids in generally good yields [15]. As a next step, the biaryl aldehydes 13a–f were converted into their corresponding oximes 14a–f in good yields as a mixture of (E) and (Z

• was demonstrated to be useful for the synthesis of the natural product trisphaeridine (3) [17]. Exposure of 1-bromo-2,4,5-trimethoxybenzene (19) to Suzuki–Miyaura coupling reaction conditions with boronic acid 20 resulted in the formation of aldehyde 21 (Scheme 5). Treatment of 21 with hydroxylamine

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

• synthesized the novel unactivated alkenes 4a–l containing three aryl groups as the starting materials. The synthesis of 4a is demonstrated in Scheme 1. First, 2-phenoxybenzaldehyde (1a) was synthesized by coupling reaction of phenol with commercial 2-fluorobenzaldehyde. This reaction was carried out with very

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• -(n-dodecyl)azulene (16) is shown in Scheme 5A. The Sonogashira cross-coupling reaction between 4,7-dibromo-6-(n-dodecyl)azulene (13) and 4,7-diethynyl-6-(n-dodecyl)azulene (16) yielded 4,7-polyazulene 17 linked through ethynyl bridges (Scheme 5B). Similarly, the Yamamoto cross-coupling reaction

• synthesized from tropolone (21) in five steps (Scheme 21A). The Suzuki–Miyaura coupling reaction of 2,6-dibromoazulene (125) with 2,2’-(9,9-dioctyl-9H-flourene-2,7-diyl)di(1,3,2-dioxaborolane) (103) furnished the polymer 126 in 31% yield (Scheme 21B). The other polymer 129 was obtained from 2,6-dibromoazulene

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

• ). Representative examples included indenoanthracenes 61a–c, bearing aryl groups linked to the alkyne, and indenoanthracenes 61d–f, containing tetramethylsilane groups at the terminal alkyne [46]. From commercially available 1,8-dichloroanthraquinone (62) and by using modified Suzuki–Miyaura coupling reaction

• conditions, Agarwal et al. synthesized a series of 1,8-diarylanthracene derivatives 64 in two steps (Scheme 14) [47]. First, the simple reduction of anthraquinone 62 employing the well-known reductive Zn/NH3 system and HCl provided 1,8-dichloroanthracene (63). A Suzuki–Miyaura coupling reaction in the

• ]anthracenes 139 bearing H, CN, or OMe groups at positions 11 and 12, to study their liquid crystalline properties (Scheme 32) [66]. Their methodology started with a Suzuki coupling reaction of substituted dibromonaphthalenes 136 and boronate diesters 137, to provide the corresponding 2,3-diphenylnaphthalenes

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

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• containing a stretch of four DNA nucleotides in the middle, flanked by the modifications in a ´mixmer´ design, which is important for designing gapmer ASOs [31]. Another well-established method for C-5 pyrimidine modification involves the Sonogashira cross-coupling reaction between an alkyne group and a 5

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• of the temperature. We found that increasing the temperature to 90 or 100 °C did not lead to any improvement (Table 1, entries 6 and 7). The best result for the Sonogashira coupling reaction between intermediate 2 and phenylacetylene (3a) was obtained using 0.6 mol % of Pd(PPh3)4, 1.2 mol % of CuI in

• DIPEA at 80 °C for three hours. With the optimized conditions in hand, we examined the scope of the coupling reaction of 2 with different phenylacetylenes 3b–g. As shown in Table 2, tetrahydroacridine derivatives 4a–g were obtained in moderate to good yields. The yields were better for acetylenes

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• , altogether leading to a moderate to high yield of the products (Scheme 19) [50]. A reasonable mechanism for this cyclization/coupling reaction involves the generation of a 5-copper(I)-substituted triazolide intermediate 62, which coordinates with propargyl carbonate 59. Further insertion of the C–C triple

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• C, which undergoes an oxidation process to generate carbocation D. A proton abstraction from D then affords the observed product. Cross-coupling reaction between unactivated olefins and alkyl halides under nickel catalysis The use of alkyl halides in transition-metal-catalyzed cross-couplings to

Recent advances in the application of isoindigo derivatives in materials chemistry

• Andrei V. Bogdanov and
• Vladimir F. Mironov

Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

• components of the OSC. The synthesis of such compounds is also based on the Suzuki coupling reaction between alkylated 6,6’-dibromoisoindigos and corresponding arylboronic derivatives, leading to the formation of target molecules in moderate yield (Scheme 11). In these compounds, the triarylamine substituent

• -coupling reaction (Scheme 19). However, the OSC of such a cell showed an efficiency of only 1%. Using polymeric isoindigo 35b as an acceptor component, a nonfullerene OSC was also obtained, which showed a record efficiency of 12.03% among the composites based on isoindigo described to date [55]. Polymeric

Iodine-catalyzed electrophilic substitution of indoles: Synthesis of (un)symmetrical diindolylmethanes with a quaternary carbon center

• Thanigaimalai Pillaiyar,
• Masoud Sedaghati,
• Andhika B. Mahardhika,
• Lukas L. Wendt and
• Christa E. Müller

Beilstein J. Org. Chem. 2021, 17, 1464–1475, doi:10.3762/bjoc.17.102

• via an iodine-catalyzed coupling reaction of trifluoromethyl(indolyl)phenylmethanol with indole derivatives. This method has also been extended to the synthesis of pentafluoro-ethylated and heptafluoro-propylated DIMs in excellent yields. Selected compounds were evaluated in radioligand binding

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

• :5,6-di-O-isopropylidene-ᴅ-glucose [50]. Furanoside 42 was reacted with the silyl-protected nucleobases 43a–c and 47a,b in the presence of trimethylsilyl trifluoromethanesulfonate in acetonitrile to give the 3′-azido-3′-deoxy-β-ᴅ-ribonucleosides 44a–c and 48a,b via Vorbrüggen coupling reaction. The

• -6-ynofuranoses 88a,b The ʟ-ido- and ᴅ-gluco precursors 88a,b were reacted with trifluoroacetic acid followed by acetic anhydride to afford the 1,2,3,5-tetra-O-acetyl nucleoside analogs 89a and 89b, respectively. Montgomery and Hewson base coupling reaction [60] of 1,2,3,5-tetra-O-acetyl nucleoside

• mixture of E/Z isomers. Further, double bond cleavage of nucleoside 120 followed by benzoylation produced the benzoic acid ester of the hemiacetal analogue 121 which was finally converted into double-headed nucleoside 122 via Vorbrüggen coupling reaction followed by deprotection using methanolic ammonia

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

• virtue of the Ullmann-type coupling reaction. The tribromotruxene derivative 5 was prepared from the same starting point 1 in three steps (cyclotrimerization, bromination and alkylation) using the literature reported procedures (Scheme 1). Hopefully, these three distinctly different crucial strategies

• the bromination using Br2/CH2Cl2 and then subsequent alkylation followed by Ullmann-type copper-mediated cross-coupling reaction in overall good yield (Scheme 4). On the other hand, imidazole and benzimidazole containing C3-symmetric truxene-based molecules (14 and 16) have also been assembled from

• be inspected from Scheme 7, our journey in this regard stem from the iodination of 2 using H5IO6/I2/H2SO4 in acetic acid–water solvent system to afford the desired triiodotruxene derivative 22 in 50% yield. Furthermore, Suzuki–Miyaura cross-coupling reaction of 22 with 4-formylphenylboronic acid (23

Fritsch–Buttenberg–Wiechell rearrangement of magnesium alkylidene carbenoids leading to the formation of alkynes

• Tsutomu Kimura,
• Koto Sekiguchi,
• Akane Ando and
• Aki Imafuji

Beilstein J. Org. Chem. 2021, 17, 1352–1359, doi:10.3762/bjoc.17.94

• Sonogashira coupling reaction with organic halides. The dehydrohalogenation of gem-dihaloalkanes, vic-dihaloalkanes, and haloalkenes with strong bases is often used for the synthesis of alkynes [2]. An alternative strategy for the synthesis of alkynes is the conversion of carbonyl compounds through one-carbon

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

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

• determined following a single-crystal X-ray analysis (Scheme 11). The stereoselective synthesis of diastereomeric 2-chloro-2-aroylaziridines 36 and 32 was successfully accomplished through a three-component cascade coupling reaction of silyldichloromethanes 33, arylnitriles 34 and chiral N-tert

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• functionality. Thus, this synthetic route represents the first successful Cu-mediated coupling reaction of berberine substrates. The DNA-binding properties of the 10-O-arylberberine derivatives with duplex and quadruplex DNA were studied by thermal DNA denaturation experiments, spectrometric titrations as well

• berberrubine. And herein, we report the application of this Cu-mediated coupling reaction for the synthesis of 10-O-arylated berberine derivatives as unexpected reaction product, along with first experiments that demonstrate the G4-DNA-binding properties of this class of berberine derivatives. Results and

• the Cu2+-catalyzed coupling reaction with the boronic acid (Scheme 2). The regioselectivity of the latter reaction step is most likely determined by a stronger nucleophilicity of the oxyanion in the 10-position of 6 that is caused by the particular electron distribution in the intermediate 6

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

• pathways has the advantages of mild reaction conditions and a high tolerance to functional groups, which can be exploited for artificial syntheses of biological macromolecules. In 2017, Miyake and colleagues [54] designed a type of C–S cross-coupling reaction initiated by an EDA complex promoted by visible

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• -azahexatriene system. Lastly, it was proposed that the carbodiimide 10 could be derived from urea 11. Therefore, we investigated the electrocyclization of a pyrrol-3-ylbenzene containing a carbodiimide moiety. First, 2-(pyrrol-3-yl)aniline 14 was synthesized by a Suzuki–Miyaura coupling reaction of 2

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

• and phthalazine derivatives of type 4 containing an alkylsulfanyl functional group at the 4 position, that is based on the Pd-catalyzed coupling reaction between mercaptanes and 4-bromolactams (Scheme 1, route A) [30]. In continuing our efforts on the functionalization of phthalazinones and

• Information File 1). In the next step, the bromolactams 3 were subjected to a thermal palladium cross-coupling reaction with various amines and polyamines. To optimize the reaction conditions, we investigated the reaction of 4-bromo-2-methylphthalazin-1(2H)-one (3a) with morpholine as the model substrates

• cross-coupling reaction. To confirm this idea, we carried out an experiment in which to the in situ-generated (BINAP)Pd complex (Pd2(dba)3/rac-BINAP or (R)-BINAP; 15:15 mol %) morpholine was added prior to the addition of lactam 3a. As a result, we obtained the target 4-(morpholin-4-yl) derivative 5a in

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

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

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• inhibiting activity, was prepared in yields varying mostly from 70 to 97% and always surpassing those obtained by other published methods. The method includes an Eschenmoser coupling reaction, which is very feasible (even without using a thiophile except tertiary amides) and scalable. The (Z)-configuration

• of all products was confirmed by NMR techniques. Keywords: 3-bromooxindoles; Eschenmoser coupling reaction; thioamides; tyrosin kinase inhibitors; (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones; Introduction 3-(Aminomethylidene)-1,3-dihydro-2H-indol-2-ones (3-(aminomethylidene

• desired Eschenmoser coupling reaction (route b). Therefore, the nucleophilicity of the conjugated base of the nitrogen (benzenecarbimidothioate or thioimidate) is exerted towards the oxindole carbonyl to give the thiazole. Moreover, if both benzene rings contain electron-withdrawing groups, enhancing

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• terminal amino acid, the Fmoc groups of Fmoc-Lys(Fmoc)-OH were activated with 2 × 20% of piperidine in DMF (2 mL) for 20 min, and the coupling reaction with perfluoroalkylated acids (3 equiv) or alkyl acid (3 equiv) was performed 3 times with HBTU/HOBT/DIPEA (6 equiv/6 equiv/12 equiv) for 3 h. After

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• -aminoalkylphosphonic acids 32 and 4-nitrobenyl 2-hydroxyalkanoates 33 in the presence of SOCl2 in DMF. This was an efficient coupling reaction for the synthesis of phosphonodepsipeptides from N-protected phosphonic acids and hydroxy esters. The phosphonodepsidipeptide 31 (R1 = R2 = H, Scheme 6) was converted to the

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• –Cl amide product 14. Closer inspection of the reaction progression by UV-LC–MS revealed the expected product 14 is formed first and is slowly transformed to 15 overnight. We postulated that the acidic HOAt (pKa = 3.76) liberated from the coupling reaction must be protonating thus activating the basic

• reaction mixtures were heated to 65 °C to complete the amide coupling reaction. For the least reactive anilines (e.g., compounds 24h,i), HATU only afforded trace quantities of the amide even at 65 °C. However, satisfactory results were obtained by generating the acid chloride in situ by adding a 3 fold