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

• -indole system 10, in a two-step reaction: Ugi-azide followed by a cyclization reaction catalyzed by AuCl3, in good to high yields [21]. In 2019, Salahi et al. synthesized the series of tetrazole-indoles 15 via an Ugi-azide reaction in moderate to high yields [22]. It is noteworthy that none of the

• to obtain the 1,5-disubstituted tetrazole-alkyne 19 is well-documented and hence, it is not herein described in detail [1][26][31]. Thus, based on Pal and co-workers’ proposal [32][33], the second process involves two catalytic cycles: 1) a Sonogashira coupling, and 2) a 5-endo-dig cyclization. The

• , an intramolecular cyclization takes place, facilitated by CuI. This step involves a 5-endo-dig cyclization, where the negatively nitrogen atom of the sulfonamide 25 attacks intramolecularly to yield the intermediate 26. The final product is formed when iodide is regenerated as CuI, allowing it to re

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• cyclization of aryl hydrazones with aryl isothiocyanates promoted by elemental sulfur [70]. In the course of their studies for the thiocyanation of ketene dithioacetals, Yang, Wang and co-workers developed an electrochemical oxidization-based synthetic strategy to circumvent the need for external oxidants. In

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• electrophilic sites simultaneously in their structure, these zwitterions are able to participate in various cyclization processes, especially for the synthesis of pyrroles [37][38][39][40]. For example, Li et al. developed a one-pot four-component reaction (4-CR) of malononitrile, aldehydes, and isocyanides

• ) [42][43]. Another I-MCR for forming pyrroles is the in situ formation reaction of the zwitterion III, known as Huisgens 1,4-dipole. The latter is formed by the reaction of imines with acetylenedicarboxylates and can be trapped by an isocyanide through a [4 + 1] cyclization reaction to synthesize

• pyrroles. In our recent studies, we prepared pyrrole-fused dibenzoxazepines via an Ugi reaction. Here, the reaction of benzoxazepine imine and acetylenedicarboxylate leads to the Huisgens 1,4-dipole zwitterion in situ, which is trapped by an isocyanide through the cyclization process (Scheme 1c) [44][45

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• precursors. The base-mediated reaction of 5-chloroanthranilic acid (8a) with chloroacetic acid afforded 8b (Scheme 5) [20]. Acetylation and base-mediated cyclization gave indoxyl 9a which was transformed to indigo 1c by oxidative dimerization. Benzylation finally afforded 1d. 4,6-Benzylidenation of ᴅ

• cyclization of 4e with oxalyl chloride afforded yellow isatin-N-glycoside 16a as an anomeric mixture from which the pure α- and β-anomer could be separated by chromatography. Likewise, isatin-N-glycosides 16b–f were prepared which were all isolated (except from rhamnoside 16b) as the pure β-anomers. The

• low activity was observed for oxime β-17f which is surprising, as good activities were previously reported for indirubin oximes as compared to other non-glycosylated indirubins. As mentioned above, the synthesis of acceptor-substituted isatin-N-glycosides by Lewis acid-mediated cyclization of the

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• reacts with butyllithium, ring closure occurs between the ethynyl and carbamoyl groups, yielding 2,5-disubstituted oxazole-4-carboxylates. This cyclization also occurs when the propargylamine is heated with ammonium acetate, resulting in double activation. Keywords: acid amide; diethyl mesoxalate; N

• , entries 6–8). When N-propanoyl derivative 4e was used, cyclization proceeded similarly, yielding the corresponding oxazole 5e (Table 3, entry 9). When the reaction was quenched with deuterium oxide instead of acetic acid, monodeuterated oxazole 5a-d1 was obtained (Scheme 2). Based on these experimental

• mechanism, as illustrated in Scheme 3b [13][14], we cannot negate this mechanism because the reaction media and bases were different. PCPA 4a was heated in the presence of methanesulfonic acid to undergo 6-endo-dig cyclization. However, hydration predominantly occurred, converting the ethynyl group to a

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• intramolecular cyclization were observed (Table 1, entries 3 and 4). The best results were obtained when isopropyl alcohol was used, which furnished yields of the final product 4а up to 89% within 1 h (entry 9 in Table 1). In the case of methanol and ethanol, the maximum conversion was also observed during the

• 6a, which undergoes subsequent cyclization steps more favorably, leading to the formation of the target product 4a (∆G = −3.02 kcal/mol). This suggests that the first step of intermediate formation is the critical one. It is also noteworthy that the Michael addition via intermediate 6a is an

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• , they also achieved the construction of C–N axis chirality through remote substitution/cyclization/1,5-H shift process (Scheme 26). The control experiments confirmed that the reaction requires the joint participation of copper and terminal alkyne, and the radical-capture experiment also ruled out a

• yne-allylic cation intermediate, followed by an intramolecular cyclization. The disparity in reactivity could stem from the chelation between acyclic 1,3-dicarbonyl enolates and the copper catalyst, enhancing γ-position attack in an intramolecular manner. Conversely, Meldrum's acid's rigid cyclic

• structure precludes stable copper-carbonyl interaction, favoring attack from a less hindered site. Later, Qi and Xu et al. [75] achieved highly enantioselective copper-catalyzed [4 + 1] cyclization of yne-allylic esters and cyclic 1,3-dicarbonyls, achieving remote stereoselective control through copper

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• cyclization of the indole derivatives is the most popular (Scheme 1a). For instance, the efficient synthesis of spiro[indoline-3,2′-pyrrolidines] [8][9][10] or spiro-isoxazoles [11] through different dearomatization processes has been reported. Recently, Ramana and Dothe have proposed an elegant gold

• –N bond oxidation to generate α-iminoamidines and then a final cyclization takes place (Scheme 2a). Although the synthetic procedure allowed the preparation of highly substituted complex structures under mild reaction conditions and on gram scale, it suffers from a limited structural diversity. Since

• , our plan provides: the oxidation of N-aryltetrahydroisoquinolines (N-Ar-THIQs) generating in situ the iminium ions 1, the 3C Ugi-type reaction of an electron-rich aniline, an isocyanide and 1; the subsequent oxidation of the Ugi-type product 2; and the final cyclization to give the spiro[indole-THIQs

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• was studied by UV–vis and fluorescence spectroscopy. Keywords: cross-coupling; cyclization; heterocycles; palladium; Introduction Nucleobases contain the coded information and give DNA and RNA their typical structure. As a nucleobase, uracil is involved in numerous vital processes and is therefore a

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• carbene (NHC) framework from polysubstituted aminoimidazo[5,1-b]oxazol-6-ium salts, which demonstrated strong catalytic activity in gold-catalyzed alkyne hydration and arylative cyclization reactions [14]. The synthesis of this new carbene involved the use of a novel nitrenoid reagent that was

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• deprotonates to the anion B under action of DBU. Subsequent intramolecular cyclization at the double bond of pyranone fragment leads to the formation of spiro compound C. Next, opening of the dihydropyranone ring results in pyrrolidin-2-one D which further transformed to the salt of 3-acyltetronic acid E

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• cross-coupling between these two intermediates, followed by intramolecular cyclization and subsequent deprotonation results in the desired product (Scheme 20). Furthermore, Budny and coworkers demonstrated that (±)-triticonazole and related compounds could be cyclized and alkoxylated to the

• proposed mechanism involves the one-electron oxidation of triticonazole to form a radical cation, followed by cyclization to an intermediate. Subsequent anodic oxidation forms a doubly charged cation, which is then captured by methanol and deprotonated to yield the final product (pathway A). Additionally

• cyclization of 2-ethynylanilines has been proven to be one of the most effective strategies for synthesizing indole derivatives. In this regard, Wang and coworkers developed the electrosynthesis of 3-iodoindoles from 2-ethynylanilines under mild and straightforward conditions [31]. The functionalization of

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• efficient solvent for synthesizing resorcin[n]arenes in the presence of catalytic amounts of HCl at ambient temperature and within minutes. Remarkably, resorcinols with electron-withdrawing groups and halogens, which are reported in the literature as the most challenging precursors in this cyclization, are

• tolerated. This method leads to a variety of 2-substituted resorcin[n]arenes in a single synthetic step with isolated yields up to 98%. Keywords: cavitand; cyclization; HFIP; hydroxyalkylation; resorcinarenes; Introduction The acid-catalyzed aldehyde-resorcinol condensation has been studied for more than

• limitation, we analyzed the mechanism underlying the formation of resorcin[n]arenes. The first step of the cyclization reaction is a hydroxyalkylation involving various cationic intermediates [69]. Hence, we hypothesized that any factor enhancing the rate of the first step by stabilizing carbocations will

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• reactions limit the utility of this approach. Herein, we report an intramolecular photoredox cyclization of alkenes with β-lactams in the presence of an acridinium photocatalyst. The approach uses an intramolecular nucleophilic addition of the β-lactam nitrogen atom to the radical cation photogenerated in

• intramolecular nucleophilic attack induced by photocatalytic oxidation was reported by Yoon et al. with tosylamide derivatives [29]. Specifically, amides were employed in a photoredox cyclization process using a strong photooxidative acridinium catalyst such as the Fukuzumi catalyst (I, Figure 1B) [30][31

• carboaminations. However, photoredox catalysis could be applied to a suitable β-lactam intermediate decorated with an alkene moiety to achieve N–H addition and cyclization to the fused bicyclic system of clavams (Figure 2A). Clavulanic acid (1, Figure 2B) belongs to the family of clavam β-lactam compounds and is

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• Pierre Angot, 64053 Pau Cedex 09, France School of Pharmacy and Bioengineering, Keele University, Keele, Staffordshire ST5 5JX, United Kingdom 10.3762/bjoc.20.209 Abstract A change in mechanism was observed in the hypervalent iodine-mediated cyclization of N-alkenylamides when the carbon chain between

• the alkene and the amide increased from two to three atoms. In the latter case, cyclization at the amide nitrogen to form the pyrrolidine ring was favored over cyclization at the amide oxygen. A DFT study was undertaken to rationalize the change in mechanism of this cyclization process. In addition

• , reaction conditions were developed, and the scope of this cyclization studied. Keywords: cyclization; DFT; hypervalent iodine; mechanism; proline; Introduction Proline is one of the 20 DNA-encoded proteinogenic amino acids that are essential to life [1][2]. In addition, the pyrrolidine core is present in

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• . Finally, the potential as halogen-bonding activator was benchmarked in solution in the gold-catalyzed cyclization of a propargyl amide. Keywords: diaryliodonium; gold catalysis; halogen bonding; hypervalent iodine; non-covalent interactions; Introduction The compound class of diaryliodonium (DAI) salts

• applied as catalyst for the cyclization of propargylic amide 11, a typical benchmark reaction in gold catalysis (Scheme 2) [24][25][26][27], which had previously already been activated by iodine(I) and iodine(III)-based XB donors [15][18]. To evaluate the activity of the new iodoloisoxazolium 7BArF, it

• )AuCl was applied with a catalyst loading of 2 mol %, activated by an equal amount of the DAI salt. Due to solubility issues, the reaction had to be performed in methylene chloride instead of chloroform. The gold-catalyzed cyclization reaction (Scheme 2) was followed via 1H NMR spectroscopy (Figure 3

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• complement and augment experimental chemistry. In addition to these methods, Corminboeuf and co-workers [134] proposed a genetic algorithm for the de novo design of general catalysts (Figure 14). Considering the Pictet–Spengler cyclization of tryptamine derivatives catalysed by hydrogen-bond donors, the

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• interrupted Kröhnke reaction (Scheme 1B) [51][52]. The main step of this process is an intermolecular cyclization of the formed 1,5-diketone followed by aromatization. Previously we have shown that 1,3-diketones bearing an electron-withdrawing group (EWG) adjacent to one of the carbonyls readily react with in

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• with a variety of heteroatoms. In this Perspective, we review the addition and cyclization reactions of heteroatom radicals with isocyanides and discuss the synthetic prospects of the reaction of isocyanides with heteroatom radicals. Keywords: aza-Bergman cyclization; heteroatom-mixed system; imidoyl

• radical; isocyanide; radical addition; radical cyclization; Introduction Carbon monoxide is a very important C1 resource in both synthetic and industrial chemistry and is not only capable of reacting with a variety of active species such as carbon cations, carbon anions, and carbon radicals (Figure 1

• reaction of carbon radicals with isocyanides generates imidoyl radicals as key active species [12], and addition and cyclization reactions using these radical species are useful in synthetic organic chemistry, especially multicomponent synthesis. If various functional groups can be appropriately attached

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• is that the reaction with methylhydrazine leads to two different regioisomers. Shen et al. used a concept developed by them for the C-acylation of β-ketoesters for the one-pot synthesis of pyrazoles. SmCl3-catalyzed acylation of these yields the 1,3-diketones 4, and after cyclization with hydrazine

• tolerated in this consecutive four-component reaction, as the 1,3,4-thiadiazine synthesis competes with the thiazole synthesis. Salicylaldehydes 14 and 4-hydroxy-6-methyl-2H-pyran-2-one (16) can also be used to produce 1,3-dicarbonyl compounds 18 by Knoevenagel condensation and subsequent cyclization. This

• acetylacetonate 20. Extension of the sequence by cyclization with hydrazine leads to the pyrazole products 21 (Scheme 5) [53]. The method works best with acetylacetonates, since deprotonation of other diketones with NaOEt leads to deactivation of the isothiocyanates. A limitation of the method is the formation of

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• , curcumin showcases its Michael donor–acceptor ability in different ways, such as simple Michael addition, [4 + 2] annulation, Michael addition followed by cyclization or one-pot multicomponent reactions (MCR), etc. (Scheme 1) [25]. In 2011, our group reported the reactivity of curcumin as a Michael donor

• addition–cyclization of curcumins with chalcones to synthesize functionalized cyclohexanones have been reported [28][29]. On the other hand, diastereoselective cascade Michael addition–cyclization of curcumins with α-bromonitroalkenes and α-halodicyclopentadienones afforded functionalized dihyrofurans [26

• equilibrium with 1,3-dicarbonyl enolate I, but the former would be trapped via cyclization involving a diastereoselective 6-endo-trig intramolecular Michael addition to the enone moiety leading to highly substituted cyclohexanone 3. The formation of triple Michael adduct 4 can be attributed to the enolate 3

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• versatile reagents in organic synthesis. They have for instance been frequently employed for the construction of azacycles through various cyclization protocols or cycloaddition reactions [6][7][8][9][10]. Early work in this field includes the well-known Fischer indole synthesis [11]. Additionally, they

• for constructing azacycles. Resorting to electrochemical approaches furnishes original compounds. Although the first report dates back to 1974, this tool has only been seriously considered in the last 15 years. Oxidative cyclization of hydrazones In 1974, Tabaković et al. published the oxidative

• cyclization of 2-acetylpyridine-derived N-phenylhydrazone 1a to form triazolopyridinium salt 2a [34]. The process was further applied to various 2-acetylpyridine and 2-benzoylpyridine derivatives (Scheme 1) [35][36]. The corresponding pyridinium salts 2 were obtained in high yields when the electrolysis was

Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• Abstract A flow photochemical reaction system for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence was developed, which utilizes in situ-generated 2-benzopyrylium intermediates as the photoredox catalyst and electrophilic substrates. The key 2-benzopyrylium intermediates were

• generated in the flow reaction system through the intramolecular cyclization of ortho-carbonyl alkynylbenzene derivatives by the π-Lewis acidic metal catalyst AgNTf2 and the subsequent proto-demetalation with trifluoroacetic acid. The 2-benzopyrylium intermediates underwent further photoreactions with

• [26][27][28][29] is increased. Thus, the flow photochemical process is crucial and beneficial to product formation. Recently, we reported a sequential transformation consisting of a π-Lewis acidic metal-catalyzed cyclization [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] and