Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• push–pull derivatives bearing electron-donating and electron-withdrawing groups at the para-position of the benzene rings are known to exhibit very fast thermal isomerizations [53]. Velasco and co-workers also reported that a pyrimidine-based azophenol exhibits thermal back reaction on the nanosecond

• calculations can be a powerful tool for molecular design. In this work, we newly synthesize various aza-diarylethene derivatives N3, N4, and I1–I4 with different substitution positions of the aryl group, and investigate their photochromic behaviors and thermal back reactivities as the data set for the

• thermal back reactivities on the order of sub-ms to ms as well as N1 and N2. These thermal back reaction rates are comparable to those of diarylbenzene derivatives, hexaarylbiimidazole derivatives, and naphthopyran derivatives, which are known as fast T-type molecules [41][65][66]. Investigating the ΔH

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• derivatives exhibit improved pharmacokinetic properties [17], which has further sparked interest in their development. Consequently, constructing benzimidazoles bearing the CF2H and PhCF2 groups has garnered significant attention. However, despite this growing interest, only a limited number of research

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• synthesis was efficient and rapid as the final adducts could be isolated only by precipitation. In addition, the reactions were performed in a parallel setup using custom-made metal blocks. Specifically, thienopyrimidine and thienopyrimidone derivatives exhibit a range of biological activities, i.e

• ., analgesia, anti-inflammation, antihypertension and many more (DB06889, DB07397, DB08777) [47][48][49][50][51][52][53][54][55][56]. Thienopyrimidone derivatives have also been used in the context of other Gewald-based MCRs in the past, but the reported diversity has been rather low [57][58][59][60]. The

• reaction of 2 with formamide was performed within only 3 h (Scheme 3), yielding the N-substituted thienopyrimidones 5a–e in 30–99% total yield (2 steps), as well with aliphatic and (hetero)aromatic substituents. Quinoline derivatives are prevalent in nature, and many exhibit a range of biological

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• amidation Recently, Cao and co-workers reported the copper-catalyzed synthesis of 1,2,4-triazole derivatives via an N-acyl nitrene intermediate [76]. As illustrated in Scheme 3, dioxazolones 4 and N-iminoquinolinium ylides 5 served as reactive substrates, leading to the formation of various polycyclic 1,2,4

• -triazole analogues 6. Both dioxazolones 4 and N-iminoquinolinium ylides 5 demonstrated excellent tolerance in this transformation. Notably, electron-rich dioxazolones exhibited slightly higher reactivity. The proposed catalytic cycle for the copper-catalyzed synthesis of 1,2,4-triazole derivatives is

• , styrene derivatives bearing both electron-rich and electron-poor groups underwent the desired transformation with high yields and enantioselectivities (23g and 23h). However, the styrene scaffold bearing a trifluoromethyl group showed reduced enantioselectivity (23i). Styrenes containing heterocyclic

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• , including pyridinium and its derivatives [40]. More importantly, it favors intermolecular π-stacking interactions with aromatic guests [48]. Herein, we report on a novel supramolecular dimerization motif in 2:2 stoichiometry using H-bonded aramide macrocycles for constructing orthogonal supramolecular

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• optimized conditions allowed the reaction to proceed under a constant current electrolysis at 1.5 mA for 6 hours, followed by stirring for additional 24 hours with the electricity turned off. These reaction conditions were applicable to various N-aryl-THIQ derivatives with various functional groups. Using

• asymmetric electrocatalytic cyanophosphinoylation of vinylarenes (Figure 14) [69]. In the presence of a copper catalyst and the chiral ligand sBOX(iPr) (L8) in an electrochemical cell, these three component reactions using styrene derivatives 27, TMSCN (21), and diarylphosphine oxide 80 as starting materials

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• intermediate VIII. At this stage, the amido–copper complex IX selectively attacks the intermediate providing the 1-aryl-2-sulfonamidopropane 8. This procedure is a valuable alternative to a similar approach for the synthesis of amphetamine derivatives 9 from allyl carbamates that requires excess of Cu(OTf)2 [6

• Biginelli reaction was carried out starting from salicylaldehyde providing hydroxyphenyl-substituted dihydropyrimidines 18 [30]. Subsequently, the regioselective oxidation of the dihydropyrimidine ring in the presence of CAN allowed the formation of new pyrimidinone derivatives 19. The efficacy of Cu(OTf)2

• , reacts with an enol species activated by the copper catalyst, affording the final product. The same research group reported an extension of this study by starting from arylacetylenes instead of arylketones [42]. Imidazo[1,2-a]pyridine derivatives 33 can be achieved by Cu(OTf)2-catalyzed multicomponent

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• compounds comprising a stereogenic plane or axis is much less developed. Axially chiral compounds are well known as chiral ligands in asymmetric catalysis, with notable examples of binaphthyl-based derivatives such as BINAP, SEGPHOS, or binaphthyl-based phosphoric acid derivatives, which are among the

• reacted with aminoarylaldehydes 5 to form axially chiral 2-arylquinoline derivatives 6 (Scheme 2). Using the pyrrolidine derivative C2 as the most efficient organocatalyst, a range of quinoline derivatives were obtained in high yields and enantiomeric purities. The postulated mechanism consists of iminium

• was carried out to provide the final biaryl products 17. In a related strategy, Hayashi´s team realized an organocatalytic Michael/aldol cascade leading to chiral dihydronaphthalene derivatives 20a–e [25]. Through a series of one-pot reactions, aromatization was achieved with concomitant central-to

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• atmosphere, special precautions, and with isolated yields up to 60% [14][15]. Due to the formation of side products, final purification of the amino derivatives requires the use of either multiple separation techniques, chromatography, or distillation [15][16][17][18] (Scheme 1). Differently from lithium

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• Chemistry & Environmental Engineering, Anyang Institute of Technology, Anyang 455000, China 10.3762/bjoc.20.274 Abstract A novel series of D−A−D-type 9-phenyl-9-phosphafluorene oxide (PhFlOP) derivatives was prepared and is reported herein. The synthetic protocol involved 5 steps from commercially

• HRMS spectrometry were in full agreement with the expected structures, and single-crystal X-ray diffraction analysis was conducted to confirm the structure of compound 7-H. Moreover, the photophysical properties of these PhFlOP derivatives were determined by UV–vis absorption and photoluminescence

• acceptor group in TADF emitters, indicating great potential for the development of highly efficient TADF molecules. In 2019, Nishida and co-workers prepared 5 D–A–D-type PhFlOP derivatives with electron-donating diarylamine or carbazole moieties in positions 2 and 8. They conducted optical and

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• -catalyzed annulation reaction between bromo-chloronaphthalene dicarboximides 6 and heteroarylboronic esters that enabled the syntheses of acenaphthylene-fused thiophene and indole derivatives 7 having donor-acceptor units (Scheme 1a) [40]. In 2021, Jin and co-workers developed an elegant Pd-catalyzed

• -diiodonaphthalene (12) and thiophene-3-ylboronic acid and ester derivatives 17 under the optimized conditions reported in our previous work (Table 1) [43]. Gratifyingly, the reaction worked smoothly with the use of thiophene-3-ylboronic acid (17a) to give acenaphtho[1,2-b]thiophene (15a) in 76% yield when Pd(dppf

• multi-substituted benzo[j]fluoranthene derivatives, which have the potential to be useful in natural product synthesis. However, all oxygens in compound 18 are protected as methyl ethers, and therefore, demethylating one or some of these methoxy groups selectively is anticipated to be extremely

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• reactivity, yielding numerous derivatives with wide applications [2][3][4][6][7][8]. Their enhanced stability, compared to other HIRs, is due to: (i) the molecular geometry, which allows better overlap between the non-bonding electrons of the central iodine atom and the π-orbitals of the aromatic ring [2][9

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• functionalization (LSF) of peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, as the electron-deficient olefin moiety can engage in late-stage functionalization reactions, like a Giese-type reaction. Cheap and widely available

• derivatives. Upon abstraction of a hydride from tris(trimethylsilyl)silane (TTMS) by an excited benzophenone derivative, the formed silane radical can undergo a XAT with an alkyl bromide to generate an alkyl radical. Consequently, the alkyl radical undergoes a Giese-type reaction with the Dha derivative

• photocatalyst (Figure 1d) [25]. Noël et al. [26] have further extended this approach to include alkyl bromides (Figure 1e) [26]. Despite the effectiveness of the photolysis, benzophenone derivatives have also been shown to enhance the productivity of silane-mediated conjugate additions, using alkyl halides [27

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• organolithium derivatives 2,2'-dilithio-4,4',5,5'-tetraalkoxy-1,1'-biphenyl (2Li-BPn). In a continuation of this study, aiming at testing the limits of the reaction and providing a large diversity of structures, a structurally related series of compounds is reported here, namely 1,2,4-trifluoro-6,7,10,11

• -tetraalkoxy-3-(perfluorophenyl)triphenylenes (Fn). They were obtained by reacting the above mentioned 2,2’-dilithiobiphenyl derivatives with decafluorobiphenyl, C6F5–C6F5. These compounds differ from the previously reported series, 1,2,4-trifluoro-6,7,10,11-tetraalkoxy-3-aryltriphenylenes (PHn), solely by the

• derivatives and the antiparallel stacking mode into columnar structures stabilized by arene–perfluoroarene intermolecular interactions were confirmed by the single-crystal structure of the alkoxy-free side chain analog, i.e., 1,2,4-trifluoro-3-(perfluorophenyl)triphenylene (F). UV–vis absorption and

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• % yield, respectively. The related reaction is also carried out with amides of non-pyridine derivatives terephthal- and benzamides to afford multiply fused heterocyclic compounds in 81% and 89% yields, respectively. Keywords: intramolecular C–H arylation; multiply fused heterocycles; palladium acetate

• ][7] are found in a variety of advanced materials [8][9] and biologically important molecules [10][11][12]. A wide range of pyridine derivatives have been employed as extractants of metal ions through chelation [13]. Phenanthrolines, a class of pyridine derivatives, have attracted attention for the

• effective to afford 2a in 94% yield. The reaction was then carried out with several pyridine derivatives including amide derivatives composed of 6-methylpicoline (1b) and unsubstituted picoline (1c) as summarized in Table 2. When the reaction was examined in the absence of a phosphine ligand, the yields of

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• enables the synthesis of structurally distinct cyclic derivatives which are difficult to access by other methodologies, using an efficient and atom-economical path from simple precursors. In recent years several asymmetric catalytic cyclization strategies have been accomplished for the construction of N

• cyclic derivatives. Conjugated imines are usually synthesized from the corresponding carbonyl precursors by reaction with a sulfonamide in the presence of Lewis acids and a dehydrating agent such as molecular sieves [3]. Also, recently a palladium-catalyzed dehydrogenation of aliphatic imines was

• example. This review discusses different examples involving IEDADA reactions and other cyclizations, with a special focus on the mode of action of the organocatalysts, and aims to show the synthetic applicability of the formed cyclic derivatives. The three non-covalent organocatalysts which will be

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• ]undeca-2,7,9-trien-4-ol moiety classified as psammaplysin derivatives. About 50 psammaplysin derivatives have been identified so far [2][3]. Among bromotyrosine alkaloids, the psammaplysin derivatives are particularly intriguing due to their structural complexity and biological activities. Psammaplysin

• derivatives exhibit a range of bioactivities, including antibacterial, anticancer, antimalarial, and antiviral effects. Since the discovery of the first psammaplysin derivative, psammaplysin A [4][5], these alkaloids have been recognized as challenging targets for total synthesis. The absolute configuration

• have identified various bioactive bromotyrosine alkaloids [8]. Previously, we isolated two psammaplysin derivatives, ceratinadins E and F, containing two or three 11-N-methylmoloka’iamine units, from the Okinawan marine sponge Pseudoceratina sp. [9]. Further investigation of this sponge has led to the

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• derivatives [1]. In particular, the catalytic isomerization of 5-chloroisoxazoles allows the generation of azirine-2-carbonyl chlorides, which can be easily converted into a variety of azirine-2-carboxylic acid derivatives by reactions with nucleophilic reagents. Using this approach, numerous 2-(1H-pyrazol-1

• -carboxylic acid derivatives are not only valuable synthetic building blocks [3][4][5][6][7][8][9][10][11] but also show useful biological activities [12][13][14][15][16][17][18]. Although many 2,2-bifunctionalized azirines have been synthesized [3][4][5][6][7][8][9][10][11], the synthesis of only one 2H

• only one azirine-2,2-dicarboxylic acid derivative from a certain isoxazole precursor. Herein, we would like to report a method for the synthesis of 2H-azirine-2,2-dicarboxylic acids and their various derivatives from a single starting material, 3-substituted 2H-azirine-2,2-dicarbonyl dichloride 2, via

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• % yield, and comparable yields were observed for the p-tolyl and p-chlorophenyl derivatives 3n and 3o. A slight increase in yield was found with the p-anisyl derivative (3p, 61% yield), whereas the yield decreased when the arene was appended with an electron-withdrawing CF3 group (3q, 45% yield). Though

• polyfluoroalkylated derivatives in moderate to very good (45–92%) yields. It is nonetheless crucial to underscore that the reaction developed herein was ineffective with aromatic and aliphatic variants of both keto and imino sulfoxonium ylides, and no reaction was observed in any of the attempts (see Supporting

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• tetrahydropyridazine scaffold is also found in numerous natural linear or cyclic peptides such as svetamycins or antrimycins as dehydropiperazic acid (Figure 2) [10]. Whereas many publications have been devoted to the synthesis and structure of piperazic acid derivatives (dehydro, chloro, hydroxy, …) [11][12], nothing

• feature results will be further confirmed by the insertion of these cyclic β-dehydropiperazic acids in longer peptide sequences. Examples of bioactive tetrahydropyridazine derivatives. Linear and cyclic peptides incorporating the dehydropiperazic acid moiety. Piperazic acid and analogues and target

• trifluoro/difluoromethylated tetrahydropyridazine acids. Synthetic strategy to obtain fluorinated tetrahydropyridazines from difluoro- or trifluoromethylated hydrazones. X-ray diffraction of compound 8f. Reported syntheses of tetrahydropyridazine ester derivatives. Synthesis of fluorinated hydrazones 3a–f

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• obtain α-acylaminoamides. Innovation in recent years with alternative reagents, like N-hydroxyimides or nitric acid in place of an acid, N-alkylated hydrazines, or nitrobenzene derivatives (reduced in situ to anilines) instead of amines, and in situ-prepared isocyanides, makes it a versatile method for

• reaction (Scheme 1). A wide variety of isatins were suitable for performing the 4-center 3-component Ugi reaction (U4C-3CR), as well as isocyanides. Using 3-aminopropanoic acid (or β-alanine) and 4-aminobutanoic acid (or γ-aminobutyric acid), the corresponding β- and γ-lactam derivatives were obtained

• findings reinforced the theory that developing MTDLs could provide a more effective approach for addressing complex neurodegenerative disorders than conventional single-target strategies. Knoevenagel-based multicomponent reactions: Several quinazolinone derivatives have already been developed as MTDLs

Surprising acidity for the methylene of 1,3-indenocorannulenes?

• Shi Liu,
• Märt Lõkov,
• Sofja Tshepelevitsh,
• Ivo Leito,
• Kim K. Baldridge and
• Jay S. Siegel

Beilstein J. Org. Chem. 2024, 20, 3144–3150, doi:10.3762/bjoc.20.260

• . Access to the dianion of BFC presages an interesting diradical and this was achieved by inclusion of mesityl protecting groups [27]. Extension of the BFC model with thiophene provides further interesting materials [28]. A reasonable corollary to this behavior would assert that derivatives of TBF and

• characterized via second derivatives (Hessian) analysis to establish stationary points and effects of zero point and thermal energy contributions. Effects of solvent employed the COSMO:ab initio continuum method [32][33], using a dielectric as in experiment, and fully optimized using radii of Klamt [34

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• alkyl chain. Substrates with p-tolylsulfonyl (Ts), p-nitrobenzenesulfonyl (Ns) and benzenesulfonyl (Bs) protecting groups were cyclised in high yields to the corresponding 3-fluoropyrrolidine derivatives 14. A range of unsaturated amines were successfully cyclised. However, substrates with substituents

• , Xu, Zhang, Zhu and co-workers reported a method to catalytically synthesise 5‑fluoro-2-aryloxazolines 39 by utilising BF3·Et2O as the fluoride source and activating reagent (Scheme 21) [6]. The synthesis of these derivatives was achieved with high efficiency, resulting in good to excellent yields of

• synthesis of fluorinated cyclopentane products 41 from alkenyl malonate derivatives 40. The malonate nucleophile required longer reaction times of 8 hours compared to 1–3 hours for aminofluorination and oxyfluorination, however good yields were reported. Hypervalent iodine-mediated chlorocyclisation

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• -defined binding pockets, offer a preorganized arrangement of functional groups as a suitable microenvironment for organocatalysis. In 2008, Kohnke, Soriente and co-workers first reported [37] the H-bonding organocatalytic activity of calix[4]pyrrole derivatives 3 and 4 and acyclic dipyrromethane 5 for the

• . Changes in the reduction or oxidation state can alter redox behavior, thereby affecting catalytic activity. For example, it has been reported that 2,3,5,7,8,10,12,13,15,17,18,20-dodecasubstituted free-base porphyrins and their mono/diprotonated derivatives are highly distorted with a good access to the

• ethyl groups at the β-position and C6H5 or 4-Me-C6H4 at the meso-position (26 and 28) were catalytically active, giving more than 98% conversion, whereas the planar derivatives; H2OEP (2,3,7,8,12,13,17,18-octaethylporphyrin (25)), H2TPP (5,10,25,20-tetraphenylporphyrin (18)) and all the compounds with

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• studies, we employed benzaldehyde derivatives with various stereoelectronic decoration, excluding aliphatic ones due to their decreased reactivity resulting in failures to proceed [24][25][26][27]. Commercially available isocyanides utilized were cyclohexyl and tert-butyl isocyanide. Notably, an isolation

• -disubstituted tetrazole-methanesulfonylindole derivatives, with yields ranging from 16% to 55% after purification by column chromatography. Despite some yields being modest, they are deemed reasonable considering the reaction’s structural complexity, atom economy, and the efficiency achieved in terms of time

• importance of the tert-butyl and cyclohexyl substituents in the imidazole can be deduced. According to the IC50 results presented in Figure 1, it can be seen that all cyclohexyl-substituted derivatives tested show activity. In contrast, those carrying the tert-butyl group are inactive, except for 18i and 18a