Copper-catalyzed multicomponent reactions for the efficient synthesis of diverse spirotetrahydrocarbazoles

• Shao-Cong Zhan,
• Ren-Jie Fang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 796–808, doi:10.3762/bjoc.18.80

• group in the oxindole scaffold, while these two groups exist in trans-configuration in the minor isomer 2g’. 5-Arylidene-1,3-dimethylbarbituric acids, as good dienophiles, could also react smoothly in such a catalytic system (Scheme 4a). Firstly, the three-component reaction of 2-methylindole, 5

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• bonds have been substituted with fluorine atoms. Within this family of molecules, perfluoroalkyl groups represent an industrially relevant moiety, capable of modifying the physicochemical properties of the scaffold that they are attached to. Such properties and a distinctive reactivity – or inert

• synthesis and application of three new members of the “dummy group” reagent family, based on the α-(perfluoroalkylsulfonyl)propiophenone scaffold for the perfluorobutylation (1a), perfluorohexylation (1b) and perfluorooctylation (1c) of electron-rich aromatics (Scheme 1). With the insights discussed in this

• envisioned the bimolecular nucleophilic substitution between an α-halopropiophenone as the “dummy group” scaffold and the corresponding perfluorinated sodium sulfinate salt – also visualized as the installation of the photocleavable moiety onto the perfluoroalkyl chain [15][16][17][18][19]. The precursory

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• major isomers 3l (Figure 1), 3s (Figure 2), and 3f’ (Figure 3) were determined by X-ray diffraction analysis. As can be seen from Figure 1 and Figure 2, the aryl group exists in the trans-position of the carbonyl group of the oxindole scaffold in the newly formed cyclohexyl ring. On the other hand, the

• aryl group exist on the cis-position of the carbonyl group on the exocyclic C=C bond (Z-configuration). Thus, it can be concluded that the major isomers 3a–z have this kind of the relative configuration. In Figure 3, the aryl group and the carbonyl group of the oxindole scaffold also exist on trans

• this work. Firstly, the nucleophilic addition of tributylphosphine to the bis-chalcone gives the active zwitterionic species (A). Secondly, the Michael addition of the zwitterionic species (A) to isatylidene malononitrile at the C3-position of the oxindole scaffold results in adduct (B). Thirdly, the

Cholyl 1,3,4-oxadiazole hybrid compounds: design, synthesis and antimicrobial assessment

• Anas J. Rasras,
• Mohamed El-Naggar,
• Nesreen A. Safwat and
• Raed A. Al-Qawasmeh

Beilstein J. Org. Chem. 2022, 18, 631–638, doi:10.3762/bjoc.18.63

• enhanced the biological activities like anticancer [15][16], antibacterial [17], antimalarial [18], anti-inflammatory [19], and lead to a promising scaffold for the treatment of Alzheimer’s disease [20]. Our previous work showed that a combination between cholic acid and heterocyclic scaffolds improved the

Unusual highly diastereoselective Rh(II)-catalyzed dimerization of 3-diazo-2-arylidenesuccinimides provides access to a new dibenzazulene scaffold

• Anastasia Vepreva,
• Alexander S. Bunev,
• Andrey Yu. Kudinov,
• Grigory Kantin,
• Mikhail Krasavin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2022, 18, 533–538, doi:10.3762/bjoc.18.55

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• ], cucurbiturils [24][25], and cavitands [26][27] have been widely applied. While these conventional macrocycles can usually enable a confinement effect or serve as a supporting scaffold, they do not contain definite catalytic sites in their cyclic skeletons. When required, an additional catalytic functional group

• was commonly introduced through in-situ, noncovalent inclusion/encapsulation in the cavity or by covalent, post-functionalization of the macrocyclic scaffold. The encapsulated catalytic group could occupy the space for substrate entering, or has a risk to be squeezed out of the cavity under complex

• catalytic conditions. On the other hand, the covalently pendant catalytic group may reside far away from the center of the cavity. On the other hand, we envisaged by use of tailored building units already containing definite catalytic sites to directly form a macrocycle scaffold could provide a different

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• and operational simplicity through one pot reaction. Keywords: chemoselective conjugate reduction; dispirocyclopentanebisoxindole scaffolds; metal-free; one-pot operation; reductive cyclization; Introduction There is a vast demand of the structurally complex spirooxindole scaffold which is an

Comparative study of thermally activated delayed fluorescent properties of donor–acceptor and donor–acceptor–donor architectures based on phenoxazine and dibenzo[a,j]phenazine

• Saika Izumi,
• Prasannamani Govindharaj,
• Anna Drewniak,
• Paola Zimmermann Crocomo,
• Satoshi Minakata,
• Leonardo Evaristo de Sousa,
• Piotr de Silva,
• Przemyslaw Data and
• Youhei Takeda

Beilstein J. Org. Chem. 2022, 18, 459–468, doi:10.3762/bjoc.18.48

• , the one-less number of donor units in the molecular scaffold led to lower solubility in organic solvents and thermal stability, presumably due to the less steric hindrance around the π-extended conjugated acceptor unit with the unsymmetric molecule structure. The OLEDs fabricated with the D–A emitter

Synthesis of 3,4,5-trisubstituted isoxazoles in water via a [3 + 2]-cycloaddition of nitrile oxides and 1,3-diketones, β-ketoesters, or β-ketoamides

• Md Imran Hossain,
• Md Imdadul H. Khan,
• Seong Jong Kim and
• Hoang V. Le

Beilstein J. Org. Chem. 2022, 18, 446–458, doi:10.3762/bjoc.18.47

• prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism for the selectivity of the [3 + 2]-cycloaddition reaction to produce 3,4,5-trisubstituted isoxazoles. Not to be overlooked are our optimized reaction conditions for the dimerization of hydroximoyl

• . Meanwhile, some of the starting material 2l remained unreacted and we suspected the lower solubility of compound 2l in water was responsible for the low yield of the reaction. Since trifluoromethyl-substituted isoxazoles are an important and prevalent scaffold in biomedical research and drug discovery

• similar 3,4,5-trisubstituted isoxazole structure to the synthesized compounds in this report. In addition, we optimized the reaction conditions to produce trifluoromethyl-substituted isoxazoles, a prevalent scaffold in biomedical research and drug discovery programs. We also proposed a plausible mechanism

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

• because the parent system does not operate in the spectrum of the sunlight. Therefore, the efficient and purposeful functionalization of the norbornadiene scaffold is an important and challenging task in this field. Specifically, earlier approaches for the synthesis of norbornadiene derivatives are mainly

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• -type siderophores. Structurally, compounds 1–5 are closely related to formobactin [10], brasilibactin [23], nocardimicin [24], and terpenibactins [15]. While the core scaffold of these natural products is conserved, they differ in the length of their fatty acid residues, their methylation pattern, and

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

• dictate the position of the metal centers, we reasoned on the possibility to design a novel generation of diametric phosphine gold(I) cavitands exploiting a calix[6]arene scaffold characterized by a 1,2,3-alternate conformation. As working hypothesis, this geometry would segregate two catalytically active

• calix[6]arene scaffold, we carried out the synthesis of three monomeric gold catalyst analogues A’,B’,C’(AuCl). The synthesis of these compounds was performed using the previously optimized protocol, starting from a 4-(octyloxy)aniline intermediate (Scheme 2). Subsequently, due to the general interest

• parental macrocycles A,B(AuCl)2, that arise from the proximity of the two gold(I) nuclei to the calix[6]arene scaffold. Although just preliminary, these results indicate that the conformational properties of this class of macrocycles can influence the selectivity in gold(I)-catalyzed cycloisomerization of

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• scaffolds with versatile medicinal properties, including anti-Alzheimer, anti-inflammatory, anticancer, antidiabetic, and antileishmanial activity [1]. Since the first synthesis of paullones (scaffold A in Figure 1) in 1992 [2], and disclosure of their Cdk inhibiting potential, several other analogues were

• From a retrosynthetic point of view, we followed three main pathways, in order to accomplish the synthesis of scaffold C. The first retrosynthetic route (a) started with an alkyl halide precursor, which was expected to afford scaffold C after ring-closure reaction at position 2 of the indole ring [23

• -oxobutanoate (Scheme 1). To construct scaffold C by route (a) we first tried to synthesize 3-(2-nitrophenyl)indole by Heck reaction of indole and o-iodo-nitrobenzene [25]. However, in this case we obtained an isomeric mixture of 3- and 2-(2-nitrophenyl)indole in a 3:1 molar ratio, quite difficult to separate

Green synthesis of C5–C6-unsubstituted 1,4-DHP scaffolds using an efficient Ni–chitosan nanocatalyst under ultrasonic conditions

• Soumyadip Basu,
• Sauvik Chatterjee,
• Suman Ray,
• Suvendu Maity,
• Prasanta Ghosh,
• Asim Bhaumik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 133–142, doi:10.3762/bjoc.18.14

• (NPs) and therefore automatically increases the dispersibility of the catalyst throughout the medium, resulting in a higher catalytic activity [23]. 1,4-DHPs are considered one of the most useful molecular scaffolds in medicinal chemistry. The scaffold is the main constituent of several crucial drugs

1,2-Naphthoquinone-4-sulfonic acid salts in organic synthesis

• Ruan Carlos B. Ribeiro,
• Patricia G. Ferreira,
• Amanda de A. Borges,
• Luana da S. M. Forezi,
• Fernando de Carvalho da Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 53–69, doi:10.3762/bjoc.18.5

• -hydroxynaphthoquinomethanes [110]. These reactions were carried out by method A described above, and the stereochemistry was attributed to the E-isomer (Scheme 19). Conclusion Compounds containing the 1,2-naphthoquinone scaffold represent a class of natural and synthetic substances with important biological activities and

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• scaffold. Selected examples of bioactive spirobarbiturates. The screened organocatalysts. X-ray crystal structure of 3ae (displacement ellipsoids are drawn at the 50% probability level). Known strategies and conceptual advance of this contribution. Substrate scope of 2-isothiocyanato-1-indanones. The

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• this purpose, tryptophan halogenases RebH and Thal were applied for the generation of ʟ-7-bromo- and ʟ-6-bromotryptophan, respectively. As a peptide sequence, we chose the β-catenin-binding domain (CBD) of axin as a benchmark system (PDB ID 1QZ7) [75]. Axin is a scaffold protein playing an essential

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

• Rodolfo H. V. Nishimura,
• Thiago dos Santos,
• Valter E. Murie,
• Luciana C. Furtado,
• Leticia V. Costa-Lotufo and
• Giuliano C. Clososki

Beilstein J. Org. Chem. 2021, 17, 2968–2975, doi:10.3762/bjoc.17.206

• ) with relevant biological activities, is recognized as a privileged scaffold in medicinal chemistry [3][4]. Among important quinazoline derivatives, 4-anilinoquinazolines have been widely investigated as antitumor agents because they can inhibit some receptor tyrosine kinases (RTKs) expressed by

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• , ensuring the smooth progress of the total synthesis of hoshinoamide A. With the tripeptide 7 in hand, we went on to construct the peptide scaffold (Scheme 3). When tripeptide 7 was subjected to Pd-catalyzed hydrogenation conditions [16], the benzyl group was selectively cleaved to generate 8. Treatment of

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

• would give the oxindole scaffold. Hydrogen abstraction would regenerate the reduced iron catalyst and produce the final product. Two years later, Zhou and co-workers expanded the reaction for the synthesis of substituted isoquinoline-1,3(2H,4H)-dione derivatives 64 (Scheme 10) [81]. Both laboratories

• of functional groups with neither EDGs nor EWGs altering the reactivity of the acrylamide. Once synthesized, the authors demonstrated the oxindoles could be transformed into fused indoline–heterocycle frameworks in good yield, an attractive scaffold found in many biologically active compounds [119

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• , according to Temel and co-workers who studied a similar scaffold, namely, 4-bromo-2-((quinoline-8-yl)methyl)phenol [27], no imine–hemiaminal tautomer peak transition was observed for the Schiff bases 3. In general, there were slightly significant changes in the transitions according to the changes in the

Synthesis of new pyrazolo[1,2,3]triazines by cyclative cleavage of pyrazolyltriazenes

• Nicolai Wippert,
• Martin Nieger,
• Claudine Herlan,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2021, 17, 2773–2780, doi:10.3762/bjoc.17.187

• [3,4-d][1,2,3]triazines and their derivatives, for example, were reported to function as anticancer compounds [28][29][32], herbicides [19][20][21], antimicrobials [18], and pest control agents [35]. Several possibilities have been reported to gain the scaffold of pyrazolo[3,4-d][1,2,3]triazines

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

• ] receptors. They are useful in the synthesis of phosphorescent materials [22][23][24], fluorosensors [25]. and also found as chiral ligands in a variety of transition metal catalysts [26][27][28][29][30]. Given the pharmacological promiscuity of this scaffold, extensive efforts from different groups led to

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

• synthesis of atropisomeric heterobiaryls 2.1. Synthesis of atropisomeric arylindoles The indole scaffold is found in many natural products, drugs, and bioactive molecules. Moreover, the introduction of axial chirality into the indole scaffold is receiving attention due to its widespread use [45][52]. In

• bioactive molecules and chiral catalysts [62][63][64], the construction of this scaffold has recently become valuable and attracted the attention of chemists [2][64]. In this context, Shi and co-workers reported a new strategy for the enantioselective synthesis of axially chiral naphthylindoles via the

• scaffold for a variety of natural products, bioactive compounds and pharmacological agents [79] as well as for a variety of chiral phosphine ligands [80]. As a result, the preparation of axially chiral arylpyrroles has been one of the most important areas of investigation in synthetic chemistry. In the

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

• presently discussed as a therapeutic option for fighting Ebola and SARS-CoV-2 viruses [12]. Modifications of the tilorone scaffold resulted in compounds having cytokine-inducing [13], antitumor [14], and telomerase-inhibitory effects [15]. Further synthetic fluorenones and polyfluoren(on)es show attractive