Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• carboxylate groups followed by a ring opening of the aziridine ring, forming azomethine ylide intermediates A. The intermediates A further undergo a [2 + 3] annulation (or cycloaddition) with aldehydes 2 through endo transition state TS to generate intermediates B, which release products 3 with regeneration

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• using tris(2,4,6-trimethoxyphenyl)phosphine (TMPP) to obtain methyl cinnamate (44) in good yield (Scheme 18) [50]. Herein, the phosphine group attacks the acid fluoride to give intermediate 55, fluoride attack then triggers methoxy group release. Toste and co-workers (2021) synthesized N-trifluoromethyl

• trimethylsulfoxonium iodide (TMSOI) with DMSO-d6, resulting in CH3/CD3 exchange. Furthermore, Chisholm and co-workers (2019) synthesized bulky cinnamate esters 61–64 utilizing a trichloroacetimidate-based alkylating agent in moderate to excellent yields via carbocation 65 formation upon trichloroacetamide release

• ) utilized isothiocyanate and cinnamic acid (7) to prepare the corresponding amide 47 in good yield via a carbamothioic anhydride 74 formation followed by carbonyl sulfide (COS) release (Scheme 24A) [59]. Similarly, Zhao and co-workers (2020) employed tetraalkylthiuram disulfides to synthesize amides via COS

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• ]. In 2015, García-Valverde and co-workers described an alternative synthesis of benzo[e][1,4]diazepines 6, exploring the nitro group of 2-nitrobenzoic acid as a masked amino group. The release was achieved through the post-Ugi reduction of the nitro group with SnCl2 triggering concomitant

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• afforded phenanthridinones. Intriguingly, switching to the electron-rich bidentate ligand bis(diphenylphosphino)methane (dppm) redirected the pathway to yield acridones. Time-dependent NMR studies revealed that the selectivity hinges on the aryne release kinetics from its precursor. Employing CsF

• , oxidative addition of the C–I bond to palladium formed the four-membered aryl–palladium complex Int-5. Steric hindrance from the bulky dppm ligand, combined with slower aryne release (using KF as the fluoride source), attenuated aryne coordination. Under these electron-deficient conditions, CO

• to substrate 11, followed by oxidative addition and release of carbon dioxide to form the zwitterionic π-allylpalladium intermediate Int-21. Under the reaction conditions, silyl triflate 12 undergoes a fluoride-mediated 1,2-elimination to generate the cyclic allene intermediate Int-22. Through a

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• solution into chloroform and controllable release into acidic solution [32]. Very recently, it was found that the receptor L alone can further extract solid Li2SO4 into DMSO solution [33], where sulfate binding is sufficiently strong to drive the solid–liquid extraction. DFT calculations suggest that an

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• isoforms of NOS named according to their site of existence and include inducible NOS (iNOS), endothelial NOS (eNOS), and neuronal NOS (nNOS) [4]. For example, upon bacterial infection in humans, immune cells express iNOS which promotes the release of NO causing inflammation [5] and NO supports defense to

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• species Int C or Int D, which undergoes an SN2'-like pathway with allylic phosphates 23 to generate the chiral products 43 or 44 along with the release of L*CuOR species. A σ-bond metathesis of this alkoxycopper species with HBpin and/or PMHS regenerates the L*CuH catalyst, completing the secondary

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• trodelvy, used in a treatment for patients with triple-negative breast cancer, the linker may release the drug prior to internalization. (3) Payload: The payload may be a subunit used in cellular tracking, imaging, or most commonly toxic drug therapeutics. The overall goal of ADCs is to deliver the payload

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• grinding serves to dissociate the more loosely bound 2.3 from 2.2, where a release of strain energy and formation of a more thermodynamically stable 2.1·2.2 complex for a subsequent turnover are favored. The first preparative example of photomechanochemistry via manual grinding was reported by Wang and co

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• release [216] and even switch catalysis on and off [196]. MOCs containing peptides in the edge pieces also look promising to direct catalysis [217]. Extended frameworks Metal-organic frameworks (MOFs) [218][219] and covalent organic frameworks (COFs) [220][221][222][223][224] are well-studied as

• that might permit tuning of several consecutive catalytic steps [395], induced-fit binding, product release, allostery [396][397], or signaling. For the acyl transfer reaction, cage 1 is an inferior catalyst compared to cage 2, which we have postulated is due to the larger equilibrium cage height

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• , red-light photocatalysis enables innovative applications in phototherapy and controlled drug release, exploiting its tissue penetration and low cytotoxicity. Together, these developments underscore the versatility and impact of red-light photocatalysis, positioning it as a cornerstone of green organic

• photocatalysts, such as helical carbenium ions and advanced nitrobenzofuran derivatives for applications in phototherapy and controlled drug release, underscoring the potential of red-light photocatalysis in biomedicine. Review Red-light photocatalysis with metal-based complexes Metal-based complexes naturally

• acetone, allowing the pre-activation of the ruthenium complex with the successive release of an N-heterocyclic carbene ligand and a chlorine atom, which are replaced by two acetone molecules to form compound 2. Simultaneously, excitation of the osmium(II) complex in the red region (660 nm) decreases its

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• a phenol moiety. The final step is assumed to be facilitated by the release of the ring distortion of the benzofuran system. Overall, triggered by the gold(I)-promoted 6-endo hydroamination between the 2,3-diaminobenzofuran and the alkyne in 11, dehydrogenative oxidation of the resulting 12 to form

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

• noncovalent bonding interactions. It also confers on supramolecular assemblies with higher complexity and multilevel ordering [9][10][11], leading to a vast number of applications, for example, for use in detection and separation [12], sensing [13], photocatalysis [14], release [15], and as thermochromic and

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, atroposelective aza-Michael addition, and intramolecular aldol reaction to form the cationic intermediate Int-6. Release of the catalyst C2, reduction with NaBH4, and dehydration with acetic acid leads to the desired product 6. Recently, an organocatalytic atroposelective intramolecular (4 + 2

• intermediate Int-9. As the assumed rate-determining step the intramolecular nucleophilic addition takes place, followed by further cyclization and finally, release of the organocatalyst to form the axially chiral product 9. Various aryl-substituted indolines 9 were obtained in good yields and high enantiomeric

• dehydration, release of the chiral acid, and aromatization through tautomerization of intermediate Int-50 generate the desired product 195. Kwon et al. compared the effectivity of traditional biaryl phosphoric acid C30 with peptide phosphoric acid C46 in the cyclodehydration of trifluorophenylaminoacetals

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• , characterized by a concave shape with a central cavity [1]. Such structures hold significant potential for drug delivery applications as nanomotors, offering both encapsulation capability and controlled release functionalities [2][3]. Moreover, researchers have explored novel shapes utilizing PEG-PS copolymers

• holds profound implications for drug delivery and beyond. By tailoring vesicle morphology to specific requirements, researchers can optimize drug encapsulation, targeting, and release, advancing the efficacy and precision of therapeutic interventions. Continued exploration of these versatile materials

• , triggering the release of water molecules from the hydrophilic layer. Consequently, enhanced interactions between polysarcosine chains ensue, culminating in a more rigid and less permeable membrane structure at an optimum dehydration at 70 °C. This augmented membrane permeability facilitates the buildup of

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

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

• synaptic vesicle protein that is required for normal synaptic function, interfering with the release of the neurotransmitter [71][72]. Ugi reaction: Cioc et al. [73] recognized the 2-oxo-1-pyrrolidino acetamide structure of levetiracetam as a potential Ugi scaffold and aimed to construct racetam

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

• -containing [2]staffane in the solid state. Keywords: pentafluorosulfanylation; [1.1.1]propellane; radical chain oligomerization; staffanes; strain-release; Introduction In various radical additions of X–Y across [1.1.1]propellane (1), functionalized oligomers known as [n]staffanes – with n > 1, where n

• 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

• cooling; this highlights that the [2]staffanes synthesized during this study are also interesting from a fundamental structural standpoint. Results and Discussion Over the past few years, our group has begun to establish strain-release pentafluorosulfanylation as a viable strategy for C(sp3)–SF5 bond

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• converted into photoisomers with higher energy upon absorption of light. In turn, this reaction is reversible, thus allowing to release the stored chemical energy as heat in a specifically triggered back reaction [7][8][10][11][12][13]. For a practicable MOST system, some key parameters have to be ensured

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• thioesterase (TE) domain and determines the topology of the final NRP product. The TE may release the NRP as a linear peptide or cyclic peptide, and the latter further manifests many possible topologies (Figure 5b). In a nutshell, offloading is a TE-catalyzed nucleophilic attack to release an NRP from the

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

• the entire solution derived from the release of the dumbbell 13 after the decrosslinking. This fluorescence wavelength change was induced by the solvation of the dye moieties. Since the dumbbell contains the push-pull type substituents on the biphenyl structure, this dye showed solvatochromism

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

• subsequent β C–C scission of radical B produces the β-keto radical E, driven by strain release. Further alkene 127 adds the β-keto radical E to form the C-centered radical F. The Fe(III)OO-t-Bu complex D resulted from the Fe(II)/Fe(III) catalytic cycle reacts with radical F to yield the target product 129. A

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

• carbohydrate moiety is later hydrolytically cleaved in the cell to release the indirubin which then acts as a CDK inhibitor. A synergistic effect of plasma-activated medium (PAM) and β-33b on human skin cancer cells was observed [32][33]. With regard to viability, adhesion capacity, apoptosis and G2/M cell

• negative feed-back loop by TRAIL and an upregulation of both receptors. In addition, a loss of mitochondrial membrane potential and release of cytochrome c was observed which gave rise to an activation of intrinsic apoptosis pathways. The mitochondrial response seems to be related to an upregulation of Bax

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• -depleting sulfur dioxide as side products [46][47]. Later, Ichikawa and co-workers established the release of difluorocarbene from TFDA with catalytic amounts of an N-heterocyclic carbene and a base (Scheme 1C) [29][48][49]. In these reactions, difluoromethyl enol ethers were obtained, which were

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

• enolization of benzofuranone 3 in the presence of a base produced intermediate A. The latter reacted with hydroperoxide to form B with the concomitant generation of the radicals, which further reacted with intermediate B to form intermediate C. Finally, C is hydrolysed with the release of one molecule CO2 and