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

• performance. In their contribution “Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs”, Moutayakine and Burke described a new synthetic route for the synthesis of 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone (DBDAP

• ) derivatives, which possess recognized pharmacological properties [12]. They used sequential reactions catalyzed by palladium and copper. The process involves an initial amination, which can be carried out via either the Buchwald–Hartwig or the Chan–Lam reaction, followed by a palladium-catalyzed

• -dihydro[1,3]thiazolo[4,5-b]pyridine derivatives that exhibited strong herbicidal activity against commercially significant grass weeds in preemergence greenhouse tests. The synthetic route for this new family of compounds was developed and optimized, involving several reaction steps, included Pd-catalyzed

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• -hydroxybenzophenones are conventionally prepared via Fries rearrangement of a phenyl ester [10]. Organocatalytic methods have also been reported for the synthesis of 2-hydroxybenzophenones [11]. In addition, several metal-mediated methods for their synthesis have been reported. For example, the Rh-catalyzed

• rearrangement of 2-aryloxybenzaldehydes yielded 2-hydroxybenzophenone [12]. Pd-catalyzed o-hydroxylation of benzophenones gave moderate yield of the title compound, and Br-substituted substrates were found to be not compatible with this method [13]. Various metals (Rh, Cu, Ir etc.) were applied to catalyze the

• oxidative coupling of salicylaldehyde with arylboronic acids to successfully produce 2-hydroxybenzophenones [14]. Recently, a Ni-catalyzed decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones emerged as an innovative route to access 2-hydroxybenzophenones [2]. The use of transition metals poses

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• the amino group is involved in the formation of an intermediate hydroxylamine derivative. Scheme 3 demonstrates a possible reaction mechanism using the example of the peroxydisulfate oxidation of MU and TMU catalyzed by PcM. It is proposed that PcM provides the necessary polarization of peroxydi(mono

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• should allow us to introduce the molecular diversity on the anilino moiety in the last step through a palladium-catalyzed reaction (Scheme 1). Therefore, we prepared first the core structure 3 in two steps from the commercially available fluoronaphthalene 1. Metallation, followed by trapping with DMF

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• variety of transition-metal-catalyzed reactions and photoredox reactions using arylboronates as aryl sources have been energetically investigated for the construction of carbon–carbon or carbon–heteroatom bonds [12][13][14][15]. The preparation of arylboronates often requires pre-functionalized substrates

• with halogen or triflate groups. Recently, transition-metal-catalyzed direct borylation of arenes via C–H bond activation has been reported, although the design of the substrate and ligands is somewhat complicated [16][17][18][19][20][21][22]. Since the complete removal of catalyst-derived metal

• diborons can capture the in situ-generated carbon-centered radicals [28][29][30][31][32][33][34][35][36]. Among the aryl sources in organic synthesis, triarylbismuthines are shelf-stable and easy-to-handle reagents with appropriate reactivities in transition-metal-catalyzed reactions and radical reactions

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

• [3]. Transition-metal-catalyzed LSF strategies have been well-established over the past decades. More recently, with the vigorous development of photochemistry and electrochemistry, numerous innovative reports on LSF using photo-, electro-, and photoelectrochemistry have emerged. These areas have

• pharmaceutical drugs and natural products. We classify these advancements into three types: anodic oxidation, cathodic reduction, and paired electrolysis (Figure 1). This review considers direct electrolysis (oxidation or reduction), mediator-induced electrolysis, and metal-catalyzed and photocatalyzed

• product (Scheme 15). The synthesis of aziridines can be achieved via the formation of nitrenes in either a metal-catalyzed or metal-free fashion. In this context, Wickens and colleagues presented a remarkable dication pool strategy for accessing N-alkylaziridines via metastable dicationic intermediates

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

• 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

• molecular recognition [12][46]. Despite extensive research, challenges remain in the acid-catalyzed resorcin[n]arene synthesis, for example: 1) reaction times for simple resorcin[n]arenes starting from aliphatic aldehydes and resorcinol generally require multiple days and up to a week (Scheme 1a) [9][26]; 2

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

• intramolecular photoredox reaction. Photoredox-catalyzed intramolecular N-alkylation reactions of various β-lactams. The trans/cis dr was determined by 1H NMR analysis of the crude reaction mixture. Synthesis of the model substrate 14 and its photoredox-catalyzed intramolecular N-alkylation reaction. The trans

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

• -catalyzed cyclization of N-allylamides 1 and N-homoallylamides 2 to 2-oxazolines 4 and dihydrooxazines 5, respectively (Scheme 1A) [15]. We also reported that an N-bishomoallylamide 3 (n = 3) was cyclized under the reaction conditions, but in just 30% yield. It turned out that the product of this reaction

Homogeneous continuous flow nitration of O-methylisouronium sulfate and its optimization by kinetic modeling

• Jiapeng Guo,
• Weike Su and
• An Su

Beilstein J. Org. Chem. 2024, 20, 2408–2420, doi:10.3762/bjoc.20.205

• with increasing H2SO4 mass fraction, which aligns with the findings from previous studies on mixed acid-catalyzed nitration reactions [32][33]. However, the data also reveal a decline in rate constants when the H2SO4 mass fraction exceeds 94%, suggesting a complex interaction at higher acid

• different temperatures are shown in Table 2. The value of k0 increases with increasing temperature and the value of n remains almost constant with temperature, which is consistent with the results reported in previous studies for other mixed acid-catalyzed nitration reactions [17][39]. According to the

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

• it with our known iodonium species in the activation of Au(I)–Cl bonds. Results and Discussion As immediate precursor to the target structure 7Z, the literature-known isoxazole 10 was synthesized via a Cu(I)-catalyzed cycloaddition between (2-iodophenyl)acetylene (8) and benzyl nitrile oxide, which

• )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

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• previously found that the reaction between 3,5-di-tert-butyl-6-methoxymethylcatechol and different functionalized thiols occurs via an acid-catalyzed mechanism and leads to corresponding thioethers with methylene linker [53][54]. Hybrid structures of this type are of particular interest from the point of

• –80%) (Scheme 1a). The reaction between 3,5-di-tert-butyl-6-methoxymethylcatechol and 2-mercapto-4-phenylthiazole or 3-nitropyridine-2-thiol occurs via an acid-catalyzed mechanism and leads to corresponding thioethers 4, 5 with methylene linker in a good yield (80% and 63%, correspondingly) (Scheme 1b

• with heterocyclic thiols leads to the formation of S-functionalized catechols. In the case of the acid-catalyzed reaction between 3,5-di-tert-butyl-6-methoxymethylcatechol and mercapto-substituted thiazole or pyridine derivatives, catechol−thioethers are formed with an additional methylene bridge

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• bearing an affinity or reporter tag. To carry out this bioorthogonal reaction well-known chemistries were developed including traceless Staudinger ligation, Cu-catalyzed azide–alkyne cycloaddition (CuAAC), strain-promoted azide–alkyne cycloaddition (SPAAC), inverse electron-demand Diels–Alder reaction

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• studies by Bolm [12][13], and Juaristi et al. [14]. have significantly advanced chiral secondary amine-catalyzed stereoselective reactions under ball milling conditions, representing a widely explored activation mode in mechanochemical-mediated transformations. However, reports on chiral primary iminium

• [15][16] or iminium-ion catalysis [17] under ball-mill conditions are scarce, in contrast to the abundance of transformations catalyzed by such covalent catalysis. Among the numerous organocatalytic reactions facilitated by primary amine-based iminium ions, Michael-type additions deserve special

• time of two days under a pressure of 0.8 GPa [23]. Less reactive benzyl malonates, which allow for the cleavage of a free carboxylic group without the need for harsh base- or acid-mediated conditions [24], undergo additions catalyzed by primary amines [19]. However, these transformations are hampered

Deuterated reagents in multicomponent reactions to afford deuterium-labeled products

• Kevin Schofield,
• Shayna Maddern,
• Yueteng Zhang,
• Grace E. Mastin,
• Rachel Knight,
• Wei Wang,
• James Galligan and
• Christopher Hulme

Beilstein J. Org. Chem. 2024, 20, 2270–2279, doi:10.3762/bjoc.20.195

• aldehyde [10]. Latterly, Yamamoto utilized a 90% deuterated [D2]-isocyanide in a copper catalyzed [3 + 2] cycloaddition to afford a 60% deuterated [D2]-pyrrole [11]. The utility of the Leuckart–Wallach reaction towards the generation of isocyanides was first explored by Dömling [12], yet the use of such

• method to prepare [D1]-formamides (D–C=O) is through a Leuckart–Wallach reaction with an amine and [D1]-methyl/ethyl formate or [D1]-dimethylformamide [19][20]. Stockmann and co-workers produced [D2]-formamides (N–D, D–C=O) via acid-catalyzed nitrile hydrolysis with HCl and D2O [21]. Thus, using the

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• fluorobenziodoxole, are also utilized as F+ equivalents to introduce fluorine atoms into organic molecules. In addition, various trifluoromethylation reagents have been developed so far [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Transition-metal-catalyzed fluorination and trifluoromethylation methods have

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• ) [25] or β-keto esters (Scheme 1a, path 4) [26][27], the aldol reaction between aldehydes and S-ethyl acetothioate followed by oxidation with Dess–Martin periodinane (Scheme 1a, path 5) [28], the hydrolysis of α-oxo ketene dithioacetals (Scheme 1a, path 6) [29] and MgBr2·OEt2-catalyzed acylation of

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

• mainly via metal-catalyzed C–N or C–C bond formation. Despite recent advances in the area of remote C–H functionalization, this strategy still requires some pre-functionalization of the starting material or the use of directing groups [28][29][30][31][32]. An alternative strategy is based on aromatic

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• –80%) along with their preliminary photophysical (absorption, emission and time resolved fluorescence lifetime) properties. The condensation reaction for assembling the required DPMs were catalyzed with trifluoroacetic acid (TFA) at 0 °C to room temperature (rt), and the stable dipyrromethanes were

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• Biginelli synthesis of dihydropyrimidinones/thiones/selenones via acetic acid or solvent-free Yb(OTf)3-catalyzed tandem reaction of β-ketosulfone (dihydro-2H-thiopyran-3(4H)-one-1,1-dioxide), an appropriate urea, and arylaldehyde has been developed. The reaction proceeds with high chemo- and

• ) are the key methodology to access valuable heterocycles for medicinal chemistry projects. The classical Biginelli reaction (1893) is an acid-catalyzed, three-component reaction between an aldehyde, β-ketoester, and urea that produces 3,4-dihydropyrimidin-2(1H)-ones, also known as DHPMs (Scheme 1A

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

• ), but is also widely used in transition-metal-catalyzed carbonylation reactions [1][2]. However, carbon monoxide is a flammable gas with a wide explosive range, although colorless and odorless, and requires special care in handling due to its high toxicity. In addition, when carbon monoxide is used in a

• phenanthridines via silver-catalyzed radical sulfonylation–cyclization of 2-isocyanobiphenyls (Scheme 25) [98]. Wang et al. reported a radical borylative cyclization of 2-isocyanobiaryls with N-heterocyclic carbene borane (Scheme 26) [99]. The boryl radical generated via hydrogen abstraction in the presence of di

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

• conducted without solvent. In a similar approach, Khan et al. succeeded in synthesizing pyrazole-4-carbodithioates 67. The products are prepared from phenylhydrazine, aldehydes, and alkyl-3-oxo-3-arylpropane dithioates 66 catalyzed by iron sulfate (Scheme 22) [100]. In this method, aliphatic aldehydes as

• the corresponding pyrazolone derivatives, thereby providing access to both bis(pyrazolyl) and bis(pyrazolonyl)methanes. Enaminones 81 can be generated as intermediates by condensation of 1,3-dicarbonyl compounds and DMF-dimethylacetal (DMFDMA, 79). The reaction is catalyzed by the solvent 2,2,2

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

• ]. Other groups have also investigated the Michael donor–acceptor reactivity of curcumins [25]. For instance, a quinine-thiourea catalyzed Michael addition of curcumins to nitroalkenes reported by Ye et al. stopped at the single Michael addition stage [35]. In the subsequent year, Yan et al. demonstrated a

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

• engaged aromatic aldehyde-derived NH-tosylhydrazones 83 in an iodide-catalyzed electrochemical formal (3 + 2)-cycloaddition with quinolines 84 to build [1,2,4]triazolo[4,3-a]quinoline derivatives 85. Better yields were obtained with hydrazones bearing an electron-rich substituent on the aromatic ring. The