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

• activation of propargylic aldehydes with catalyst Int-1. Another critical feature was the ability of the organocatalyst to promote the Z-selective isomerization of Int-2 to Int-3. In a related fashion, Wang and co-workers developed an atroposelective heterocycloaddition [19]. The iminium-activated alkynals 4

• acylazolium intermediate Int-16 followed by E-selective protonation of Int-17 (Scheme 9). NHC-catalysis also proved useful in the atroposelective construction of triaryl derivatives with two stereogenic axes. Wei, Du, and co-workers developed a synthesis of 1,2-diaxially chiral triarylpyranones 29 via an NHC

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• -flow pattern using a Y-shaped mixer, followed by the suspension of the catalyst via a T-mixer. This technology was utilized to develop selective and efficient decarboxylative fluorination reactions. Recently, a slug flow platform was developed (Figure 3a) by injecting segments of gas as a separating

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

• challenging, if not impossible. In order to overcome this problem, we opted to synthesize benzo[j]fluoranthene analogues with differentially protected oxygens so that specific positions can be functionalized further if needed after selective deprotection. To this end, first we accomplished an efficient

• synthesis of benzo[j]fluoranthene 23 in six steps (Scheme 3). In this sequence, 1,8-DHN (19) was first converted to 1-acetoxy-8-methoxynaphthalene (24) via a selective mono-methylation of 19 followed by acetylation by acetyl chloride in 88% yield over two steps. The more electron-rich ring of naphthalene 24

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

• efficient and selective extraction of lanthanides and actinides and, furthermore, a number of heterocycles involving pyridine rings have been reported to exhibit biological activities [14][15][16][17][18][19][20][21][22]. We have recently reported, as shown in Figure 1, that the introduction of a multiply

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

• on an intramolecular Michael addition carried out in DMF and catalyzed by 10% of potassium carbonate. As previously observed [37], under these conditions, the 5-endo-trig cyclization was selective and the lactam resulting from the 5-exo-trig cyclization was not observed. Furthermore, in the case of

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

• , cholinesterase inhibition (human BuChE, hBuChE), Aβ1-42 self-aggregation inhibition, and antioxidant activity. FATH 5a (Scheme 5) emerged as a promising candidate, showing lower hepatotoxicity at 1000 µM (59.4%, 1.72-fold less toxic than tacrine), moderate and selective hBuChE inhibition (IC50 = 68.2 nM), strong

• new selective non-cannabinoid ligands due to the important motor impairment found in mice lacking GPR55 [51]. In this context, ML192 analogs were synthesized employing a divergent synthetic route starting with a multicomponent reaction, the Gewald reaction (Scheme 13). This reaction allows to easily

• heterocyclic core. The novel compounds were first evaluated using β-arrestin recruitment assays in CHO (chinese hamster ovary) cells overexpressing human GPR55. These new compounds have been evaluated in competitive binding assays for cannabinoid receptors, but all of them showed to be selective for GPR55 (>4

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• oligomerizations involving [1.1.1]propellane – i.e., to make [n]staffanes – has been notoriously challenging to control when n > 1 is desired. Herein, we report selective syntheses of SF5- and CF3SF4-containing [2]staffanes from SF5Cl and CF3SF4Cl, demonstrating cases whereby oligomerization is preferentially

• substituted BCPs [25][26][27] or photochemical appendage of 1 onto an extant BCP [28][29][30][31] are relatively effective tactics for the selective assembly of certain [n]staffanes; the main caveat is that multiple synthetic steps are required. On the other hand, while a one-pot radical chain oligomerization

• synthetic challenge. Herein, we report proof-of-concept that our previous work on strain-release pentafluorosulfanylation of 1 [36] using SF5Cl (prepared in house [37] under mild oxidative fluorination conditions [38][39][40][41][42][43][44]) can be extended to the selective synthesis of the associated

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

• cost effective and selective, one-pot transformation. Pharmaceutical uses for bio-active cyclic molecules accessible by I(III) reagents are plentiful; anticancer drugs can be formed from the basis of pyrrolo[2,3-b]indoles 1 [3][4], 2-oxazolines 2 [5][6], dihydrofuran 3 [7][8], and spirocyclic scaffolds

• . The level of this chemoselectivity was dependent on the iodane ligand: OPiv was more selective for aminofluorination than OAc, which was proposed to be due to differences in basicity and nucleophilicity (Scheme 10). Detailed mechanistic studies were carried out using multinuclear NMR spectroscopy

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

• , along with electrostatic and hydrogen-bonding interactions. This behavior not only allowed for the selective activation and deactivation of organocatalytic activity but also facilitated efficient catalyst recovery at the end of the catalytic reaction. Notably, control experiments supported the

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

• representative studies include antibacterial, anti-inflammatory, antioxidant, selective inhibitor of COX-2 [34], and anti-HIV activity [35]. In this context, even though indole is considered a privileged scaffold present in some anticancer agents [36], a few examples of methanesulfonylindoles are studied as

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• propargyltrichlorosilane without N,N-diisopropylethylamine and (b) with N,N-diisopropylethylamine. It includes Gibbs free energies (kcal/mol) and Mulliken charges (in parentheses). Metallotropic rearrangement and regioselectivity issues. Asymmetric catalytic allenylation of aldehydes. Selective preparation of

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• visible-light irradiation or heating, CD was moved back to the azobenzene moiety, and the entire process was reversible. This system was further developed in 2005 by introducing bipyridinium moieties to implement the selective transfer of the wheel via heating or light irradiation (Figure 5B) [57]. During

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• match for these dicarboxylates in terms of the zinc–zinc distance and a selective formation of 1:1 host–guest species does not occur. Nitrate, sulfate, and dithionite showed no significant binding as examples of guests without carboxylate residues (Figure S31 in Supporting Information File 1). A

• experiments (500 MHz, 500 µM, DMSO-d6, 25 °C) with mixtures of studied analytes showing the selective formation of the 1:1 oxalate host–guest complex [(C2)@L2Zn2]2− in all cases. Two-synthon approach for ligand preparation via CuAAC click reaction of an azide-functionalized, protected 8-hydroxyquinoline and a

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

• become sought-after functionalities, particularly following the multi-tone consumption in polymer production and success in medicinal chemistry. The selective introduction of a peroxide fragment at different positions on the target molecule is a priority in the modern reaction design. The pioneering

• peroxides, oxaziridines, and their derived species are often applied as terminal oxidants [7][8]. The weakness of the O–O bond allows alkoxy radicals to form through homolysis or reduction [9]. The generated alkoxy radicals provide an accessible tool for selective radical cascades, where a variety of

• photoredox catalysis [26][27][28]. These methods allow selectivity to be controlled despite the presence of the complex cocktail of radical species generated by hydroperoxides under redox or homolysis conditions. The main challenge in selective radical peroxidation is the wide range of possible pathways

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• chemistry [1][2][3]. In particular, cholesteric, i.e., chiral nematic, liquid crystals (LCs) are attractive for many display applications due to their chiroptical characteristics as well as the selective reflection of light giving rise to Bragg interference colors [4]. Cholesteric LCs can be obtained either

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• olefins, showcasing an efficient utilization of aryliodonium salts in the process. Later in the same year, Song and colleagues reported a protocol for the efficient synthesis of 2-aryl-substituted quinolines 27 and pyridine N-oxides 29 [63]. This reaction involved the selective arylation at the C2

• utilized to prepare these salts using ortho-triflate-substituted iodobenzene acetate 79. All synthesized diaryliodonium salts underwent successful aryl migrations, yielding the expected products 80 efficiently (Scheme 32). The advantages of this method include late-stage site-selective O-arylation

• therapeutics, particularly in antibody–drug conjugates (ADCs). Cysteine (Cys) holds a special place in this context due to the distinctive nucleophilicity of its thiol side chain. The cysteine thiol group offers a reactive handle for site-selective modifications, allowing for the attachment of various

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

• /Education Center for Excellence in Molecular Sciences Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China 10.3762/bjoc.20.242 Abstract The selective C–H trifluoromethylthiolation of aldehyde hydrazones afforded interesting fluorinated building blocks, which could be used as a

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

• on a Bruker Avance spectrometer at 300.13 MHz and 75.47 MHz, respectively. IR spectra were created on a Thermo Nicolet Nexus 470 FT-IR spectrometer in cm−1. Mass spectra with an HP (Agile Technologies) 5975C Mass Selective Detector were used to confirm the mass of the synthesized products. The PL

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

• . Compounds 48a–d were investigated with regard to their antiproliferative activities against lung carcinoma cells (H157) and human corneal epithelial cells (HCEC). All compounds showed a moderate and selective activity against H157 with 60% inhibition for compound 48b at a concentration of 100 µM. No

• -dihydrothiazol-5-ylidene)indolin-2-one-N-glycosides β-49a and β-49b, respectively (Scheme 32) [51]. Again, a deprotection was not possible under various conditions. Compounds 49a,b showed a moderate and selective activity against lung cancer cells H157 [52]. 3-(4-Oxo-4,5-dihydrothiazol-5-ylidene)indolin-2-one-N

• very good Z-selectivity. Employment of the pivaloyl instead of the acetyl protective group resulted in an improved yield for both steps to give S-glucoside β-54b. All attempts to deprotect compounds 54a,b failed. Compound 54a shows a moderate and selective activity against lung cancer cells H157 [52

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• for the detection of both gaseous and/or aqueous H2S are shown in Figure 1 [12][16][17]. These sensors all function via the copper sequestration mechanism, where upon addition of hydrogen sulfide to the quenched bimetallic species, luminescence modulation occurs. In our quest for highly selective

• are highly selective to HS−(aq) ions and are thus suitable for environmental or biological studies where interfering anions may be present. Gaseous H2S studies of [Tb.1·3Cu]3+ We aimed to further investigate the luminescence response of Tb3+ analogues upon exposure to hydrogen sulfide gas, building

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

• nucleophiles (Scheme 1b). However, to achieve a highly selective yne-allylic substitution, a range of challenges must be addressed. First, how to achieve the regioselectivity under the coexistence of alkenyl and alkynyl units; second, how to realize the enantioselectivity control that is remote from the

• and yne-allylic substitution. Challenges in achieving highly selective yne-allylic substitution. Yne-allylic substitutions using indoles and pyroles. Yne-allylic substitutions using amines. Yne-allylic substitution using 1,3-dicarbonyls. Postulated mechanism via copper acetylide-bonded allylic cation

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• blocks. When using them as nucleophilic reagents [15][16][17][18][19][20], the reaction between anion species, such as fluorine-containing Horner–Wadsworth–Emmons reagents, and carbonyl compounds led to E-selective olefination (Scheme 1A) [15]. On the other hand, some reactions with electrophilic

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

• amination: Direct and selective CH-aminations and amidations are challenging reactions. In this context, the regioselective sulfonamidation of (hetero)aromatic groups was achieved by the Lei group via dehydrogenative aryl C–H/N–H cross-coupling [9]. A crucial step in this transformation is the generation of

• alternative to the harsh Pummerer rearrangement. Methanol played a crucial role in achieving the desired transformation and it was suggested to promote the self-assembly of reagents 24 and 25 for the formation of 27, which allows the selective abstraction of H+ from the less sterically hindered side

• atomoxetine, metaxalone, and tadalafil. Mechanistically, thiophenol is oxidized at the anode to the corresponding radical by SET, then dimerizes into a disulfide, which is further oxidized into an intermediate cation radical, yielding a highly electrophilic species. Subsequently, a selective anisole attack

Visible-light-mediated flow protocol for Achmatowicz rearrangement

• Joachyutharayalu Oja,
• Sanjeev Kumar and
• Srihari Pabbaraja

Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213

• towards investigating for the selective elimination of the waste solvent using an integrated one-flow work-up procedure to generate 3a with maximum practicality. Initially, the individual stages of the liquid–liquid extraction was achieved using the droplet micro fluidic method for extracting the compound

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• mainly afford 2-substituted 3-hydroxyesters usually in a highly anti selective manner. Keywords: α,β-unsaturated esters; epoxyesters; fluorine; Grignard-based cuprates; nucleophiles; Introduction Fluorine-containing compounds have been utilized in diverse fields due to their special character

• ) Grignard-based cuprates. These processes usually yielded the addition products along with the epoxy ring opening at the 2 position via the SN2 mechanism, affording 3-Rf-3-hydroxyesters with the incorporation of a variety of substituents at the 2-position in a highly anti-selective fashion. We believe that