Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• lithium tetrakis(pentafluorophenyl)borate ethyl etherate LiBArF20 and sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate NaBArF24. The electron-rich, outwardly projected carbonyl oxygens of the HIM co-crystalize with the cations into bent supramolecular architectures. Both crystal structures show a

• systems, these macrocycles display dynamic behavior even in the absence of extra anions, with monomers swapping between macrocycles to participate in dynamic covalent chemistry. As a demonstration of even higher supramolecular assemblies, we also showed π-extended HIMs enable the co-assembly of

• hypothesis diverged and considered alternative binding sights including the exterior of the HIMs. Recently, Huber and co-workers [21] showed hypervalent iodine(III) compounds were not impacted by non-coordinating BArF cations. Upon this inspiration, we employed LiBArF20 and NaBArF24 as salt sources to

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

• was refluxed over sodium with benzophenone as an indicator and freshly distilled prior to use. Column chromatography was performed on silica gel (normal phase, 200–300 mesh) from Anhui Liangchen Silicon Material Co., Ltd. or basic aluminum oxide (pH 9–10) from Shanghai Titan Technology Co., Ltd

• . Petroleum ether (PE, 60–90 °C fraction) and ethyl acetate (EA) were used as eluent. Reactions were monitored by thin-layer chromatography (TLC) on GF254 silica gel plates (0.2 mm) from Anhui Liangchen Silicon Material Co., Ltd. The plates were visualized by UV light. 1H NMR (400 MHz) and 13C NMR (101 MHz

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

• 4 by utilizing pivaloyl chloride via the N-pivaloyl-activated amide 6 to give piperlotine A (5), the secondary metabolite of black pepper (Piper nigrum) reported to show antibacterial and bioinsecticidal activities, in good yield (Scheme 3A) [33][34]. In the akin process, Xu and co-workers (2023

• ) reported a carboxyl group activation of cinnamic acid (7) by applying pivalic anhydride in a single step to afford the corresponding amide 8 in excellent yield (Scheme 3B) [35]. Moreover, pivalic anhydride is easier to handle than its chloride counterpart. Wang and co-workers (2022) utilized 5-nitro-4,6

• applications in organic reactions. Similarly, Kunishima and co-workers (2021) utilized (N,N’-dialkyl)triazinedione-4-(dimethylamino)pyridine (ATD-DMAP) for the amidation of cinnamic acid (7) to generate the corresponding amide 10 in excellent yield (Scheme 5B) [37]. Mechanistically, the carboxyl group attacks

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• , lycopodine features a characteristic tetracyclic structure with a bridged cyclohexanone. To address the challenges associated with constructing the complex ring systems of this structure, She and co-workers devised an intramolecular aza-Prins cyclization strategy to form both the bridge ring and the N-hetero

• the reduction of amide-generated ketone 12 after a subsequent Dess–Martin oxidation. Upon treatment of 12 with Co(acac)2 and PhSiH3 in iPrOH at 80 °C, the Mukaiyama hydration of enamide delivered hemiaminal 13. Despite the incorrect configuration of the newly formed hydroxy group, it is considered

• column chromatography was required during this process, the synthetic route is highly practical. The enantioselective annulation of tertiary enamide 28 with enoldiazoacetate 29 was then explored under the catalysis of a chiral dirhodium catalyst. While Doyle and co-workers had previously reported an

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• ], and dyes [15][16] serve as promising structures for constructing and designing novel PCs. These structures show a high electron affinity, stability, and the possibility of tuning their physicochemical properties by substituting the two aromatic rings. In 2018, Sang Kwon and co-workers reported a

• previously reported by Zysman-Colman and co-workers [19]. Compound 5d showed the best performance with a 27% calculated NMR yield (20%, isolated yield) (Table 3, entry 3), while the azepine derivatives 5a and 5b led the transformation at 13 and 8%, respectively (Table 3, entries 1 and 2). However, these

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• Zhiyang Zhang Jialei Hu Hanfeng Ding Li Zhang Peirong Rao School of Chemistry and Chemical Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China Department of Chemistry, Zhejiang University, Hangzhou 310058, China Hangzhou DAC Biotechnology Co., Ltd 369 Qiaoxin Road, Qiantang District

• involving limonoids. Krishnolides A and C (7 and 8, respectively; Scheme 1A) were identified by Wu and co-workers from the seeds of a Krishna mangrove Xylocarpus moluccensis [26]. These two molecules belong to khayanolides, a class of rearranged phragmalin limonoids characterized by a structurally intricate

• at C10 was then introduced via a Michael addition (MeMgBr, CuI) to afford 22 in a yield of 65% (4:1 dr at C10). Initial attempts on the carbonyl 1,2-transposition protocol reported by Dong and co-workers were ineffective [45], leading to premature hydride termination and the formation of alkene 23

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

• heterocyclic peptidomimetics through various post-MCR transformations [28][29][30][31][32]. The construction of benzodiazepine cores has also been extensively explored through various post-Ugi transformations. In 2009, Torroba and co-workers developed a strategy towards β-turn mimetic benzo[e][1,4]diazepines 6

• ]. 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

• intramolecular condensation with the arylglyoxal-derived keto-carbonyl group [37]. In 2024, the same group streamlined this strategy by utilizing unprotected anthranilic acids, enabling the assembly of benzo[e][1,4]diazepines 6 directly during the Ugi reaction step [38]. In 2013, Van der Eycken and co-workers

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

• increasingly attracted attention [5][7][8][9][10][11][12][13][14], for example, in 2024, Rana [15] and co-workers reported advances in solvent-controlled stereodivergent catalysis. Surprisingly, to our knowledge, there is currently no comprehensive review of studies on controllable/divergent synthesis. This

• carbon monoxide were used as starting materials, and two natural product frameworks of phenanthridone and acridone alkaloids could be selectively obtained by controlling ligands. The reaction of o-iodoaniline with in situ-generated arynes under CO atmosphere under ligand-free conditions selectively

• , tetrabutylammonium iodide (TBAI), and water significantly accelerated aryne generation, thereby increasing its local concentration. This favored aryne coordination to the palladium center, followed by CO insertion and reductive elimination to furnish phenanthridinones. In contrast, when dppm was introduced

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• translate 2D to 3D chemical space have also been explored [48][49][50][51][52]. Here, efficient excitation, via EnT catalysis, is typically contingent on extended chromophores ≥ 4π electrons, with less conjugated systems requiring more powerful catalysts. A recent elegant example by Masarwa and co-workers

• ] cycloaddition observed, despite the use of higher catalyst loadings. The efficient isomerization of 1a during these reactions indicated that substrate lifetime for efficient intermolecular reactivity may be problematic. While substrate-tethered reactivity, developed by Brown and co-workers was unsuccessful [49

• strategies for cyclobutyl scaffolds [53][54][55], products 6 and 7 could be synthesized via mild conditions [68]. Inspired by recent advances by Nolan and co-workers demonstrating the synthetic power of gold catalysts in EnT catalysis [31][69][70][71][72], we probed the reactivity of [Au(SIPr)(Cbz)] in our

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

• found to be co-stabilized by three 18-crown-6 macrocycles. Next, a solid–liquid extraction experiment was conducted for Cs2SO4 salts. A solution of hexaurea receptor L and two equivalents of 18-crown-6 in CHCl3 were prepared, and solid Cs2SO4 was added into the solution. Under stirring at 60 °C for 5

• ion-dipole and ion-pairing are shown. Single crystal structure of complexed Cs2SO4 with 18-crown-6 and tripodal receptor L (CCDC: 2411573). One sulfate anion is encapsulated inside the hexaurea cavity through 12 × N–H···O hydrogen bonds. One Cs+ cation is co-stabilized by electrostatic interactions

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• methods, the cascade reaction between ortho-halogen (e.g., chlorine, bromine or iodine) substituted benzoic acids and amidines has become a prominent route to synthesize the corresponding quinazolinones [10][11][12][13][14][15][16][17][18]. In 2009, Fu and co-workers found that copper(I) could effectively

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• intermediates in total [29][30] and bio-synthesis protocols [31], e.g., in inositol chemistry [32] or towards aminocyclitols [33]. The potential of these compounds as functional photoswitches was primarily assessed in the 1960s and 1970s by Prinzbach and co-workers, who identified a variety of rearrangement

• Bansal and co-workers [44] revealed the potential formation of aza-QC derivatives at low temperatures. However, isolation of these derivatives proved difficult, as rapid rearrangement to azepine analogues occurred at temperatures exceeding 0 °C. On the basis of the quadricyclane or azepine structure

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• amides with electron-withdrawing or electron-donating groups on their aromatic ring, producing products with yields ranging from 51% to 82%. In 2023, Lei and co-workers [47] reported an electrochemical C–P bond formation via a coupling reaction of C–H bonds of alkynes, alkenes, and aryl compounds with

• meta or ortho positions, which may be due to steric and electronic effects. The reaction proceeded via a radical process by forming Ph2P(O)H (Scheme 16). The reaction failed to give the corresponding product when using TEMPO in the reaction mixture. Zhang and co-workers [61] reported an electrochemical

• another study, Ding and co-workers [69] recently reported an electrochemical method for synthesizing S-heteroaryl phosphorothioates without using any transition metal catalysts and oxidants at 90 °C. This method is compatible with various functional groups and can be easily scaled up to a gram scale. The

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• progressed from the original amine catalysts is the work of Shirakawa and co-workers. In this contribution, the authors employed a binaphthalene-derived sulfide organocatalyst for enantioselective bromolactonizations of α- and β-substituted 5-hexenoic acids to produce the corresponding chiral lactones [23

• ]. Kowalczyk and co-workers showed how asymmetric organocatalysis can benefit from mechanochemical activation. They established that Michael additions of thiomalonates to enones, catalyzed by cinchona-derived primary amines, is efficient and enantioselective under ball-milling conditions [24]. Kondratyev and

• ]. The enantioselective addition of propargyltrichlorosilane to aldehydes was studied by Prabhakar, Takenaka, and co-workers. This transformation was catalyzed by a biisoquinoline N,N’-dioxide catalyst, which acted as a chiral Lewis base [26]. Torres-Oya and Zurro reviewed the recent developments in

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• remains a formidable challenge, primarily due to the inherent ring strain and the difficulties associated with achieving high diastereoselectivity during cyclization [4]. Recently, Chen and co-workers developed a chiral phosphoric acid (CPA)-catalyzed multicomponent reaction of anilines, aldehydes, and

• azetidinones, enabling the efficient and enantioselective synthesis of tetrahydroquinoline-fused azetidines with three contiguous stereocenters in a single step [23]. Later, Tanaka, Nagashima, and their co-workers established a chemo-, regio-, and diastereoselective dearomative transformation of quinolines

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• fluorescent protein (GFP), has revolutionized genetics by providing highly accurate real-time detection of fusion proteins in vitro and in vivo [1]. Pioneering work on GFP-tagged proteins for real-time monitoring of gene expression was first reported by Chalfie and co-workers in 1994 [2]. For a long time

• better solubility in the reaction buffer and did not require DMSO as co-solvent, making it a very promising candidate for in vivo applications. To complete the study, and given that the mesyloxy group has shown superior efficacy over all other functional groups tested for Pepper alkylation, we

• (left side). Bar graph (right side) illustrating the relative yields of covalent tethering under the following conditions: 2.5 µM RNA, 50 µM HBC ligand, 100 mM KCl, 2 mM MgCl2, 50 mM HEPES buffer, pH 7.0, 5 h at 37 °C. The numbers in the orange bars indicate the percentage of DMSO (%) used as co-solvent

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• (CHE-1807486) for past financial support. We thank the National Institute of General Medical Sciences of the National Institutes of Health (R35GM153362) for current financial support of this project. Conflict of Interest L.I. is co-founder and holds equity in Reversal Therapeutics (National Harbor

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

• organolithium species and the other employing chiral organoboron compounds. Copper-mediated stereospecific coupling of chiral organolithium species with allylic electrophiles In the organolithium approach, a breakthrough was achieved by Knochel and co-workers through carefully controlled reaction conditions

• stereochemical integrity. Through these careful experimental controls, Knochel and co-workers effectively addressed the long-standing challenge of handling these traditionally unstable chiral organometallic intermediates. Copper-catalyzed stereospecific coupling of chiral organoboron species with allylic

• configurationally stable organoboron compounds was recently developed by Morken and co-workers, which employs only catalytic amounts of copper [47][48]. Their strategy uses chiral secondary organoboron compounds 20 as precursors to generate chiral alkylcopper species through a carefully controlled activation and

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• between 60–95% for all metal catalysis conditions. The most widely accepted mechanism is as follows: the alkynyl C–H bond is activated by the metal catalyst (Scheme 23). The metal can be added in its proper oxidation state (such as Cu(I)) or generated in situ (as in the case of Au(I), Co(I), Fe(II) and Ni

• (I)) by reducing the suitable salts (containing Au(III), Co(II), Fe(III), and Ni(II), respectively) at the beginning of the catalytic cycle. The metal in its reduced species (depicted in Scheme 23) activates the C–H bond of the alkyne. After this activation step, a weak base (like DBU, TMG, or even

• afford propargyl halide C. Finally, intermediate C reacts with the secondary amine to give the propargylamine product D. As outlined in the catalytic cycle, the presence of a base plays a dual role: co-activation of the alkynyl C–H bond through deprotonation and trapping of the HCl produced during the

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• organic chemistry [2][3][4][5], organocatalysis [6][7], metal catalysis [8][9], biochemistry [10][11], materials science [12][13], and supramolecular chemistry [14][15], although its successful application to asymmetric catalysis has been limited (Figure 1) [16][17][18][19][20]. In 2018, Arai and co

• -workers developed chiral amine 1 with an electron-deficient iodine atom, which catalyzed the Mannich reaction in excellent yields and enantioselectivities [17]. In 2020, Huber and co-workers reported the bis(iodoimidazolium) 2-catalyzed Mukaiyama–aldol reaction of carbonyl compounds with enol silyl ethers

• , which provided the products in high yields with up to 33% ee [19]. In 2023, García Mancheño and co-workers reported the tetrakis(iodotriazole) 3-catalyzed dearomatization of halogen-substituted pyridines 4, which formed the corresponding products 5 in high yields with up to 90% ee (Figure 1b) [20

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• Long K. San Sebastian Balser Brian J. Reeves Tyler T. Clikeman Yu-Sheng Chen Steven H. Strauss Olga V. Boltalina Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA ChemMatCARS, University of Chicago Advanced Photon Source, Argonne, IL 60439, USA 10.3762/bjoc.21.39

• , allows a tentative conclusion that photooxidation proceeds via dearomatization of the central ring due to the formation of the endoperoxide (Figure 4). This suggestion is also supported by a recent work of Sun and co-workers where they observed and structurally characterized the endoperoxide of 9,10-ANTH

• (trifluoromethyl)benzene (1,4-C6H4(CF3)2, Central Glass Co., 99%); dimethyl sulfoxide (DMSO, Fisher Scientific, ACS grade); anhydrous magnesium sulfate (MgSO4, Fisher Scientific); Cu powder (Strem Chemicals, 99%); dichloromethane (EMD Chemicals, ACS grade); acetone (technical grade); THF (Aldrich/Merck, ACS grade

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• solid state, which are highly dependent on molecular packing. The concept of topochemical reactions was first introduced by Kohlschütter in 1919 [1], and topochemical polymerizations were systematically studied by Schmidt and co-workers in the 1960s and 1970s [2][3][4]. Schmidt's pioneering work

• . Experimental Synthesis The studied bimanes were synthesized following the approach reported by Kosower and co-workers [17][19], and an alternative chlorination method developed by Neogi et al. [31]. The synthetic details can be found in Supporting Information File 1. Compounds were crystallized from a MeOH–DCM

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• of the electrophile. We thus identified aldehydes 9 and 10 as suitable branching points, which were easily derivatized to their aminomethyl-modified preQ1 analogs by reductive amination (Scheme 3). Their syntheses by Raney-Ni reduction of nitriles 7 and 8, previously described by Gangjee and co

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

• % yield, albeit after 72 h of irradiation. This experiment proved that 4.2 can be used in a sub-stoichiometric way, in fact acting as a catalyst. More recently, based on their previous approach via manual grinding (Scheme 2) [64], MacGillivray and co-workers adopted the vortex grinding method to enable

• exposing fresh material to light. In 2016, König and co-workers exploited rod milling to develop a photomechanochemical approach for the riboflavin tetraacetate (RFTA)-catalyzed photocatalytic oxidation of alcohols to the corresponding carbonyl compounds upon irradiation with five LEDs (λ = 455 nm) [69