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

• moieties of biologically active compounds. A salen–scandium triflate complex-catalyzed asymmetric (3 + 2) annulation of dialkyl 1-sulfonylaziridine-2,2-dicarboxylates and aldehydes generated optically active functionalized oxazolidine derivatives in moderate to good yields and good to excellent

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

• a naturally occurring plant metabolite frequently found in honey, fruits, and vegetables [1]. Cinnamic acid is biosynthesized through a shikimate pathway, catalyzed by the phenylalanine ammonia-lyase (PAL) enzyme. Generally, cinnamic acid derivatives possess a wide range of bioactivities, such as

• cinnamic acid. For example, Chen and co-workers (2020) reported the Pd-catalyzed N-acylation of cinnamic acids using tertiary amines to generate the corresponding amides 83 and 84 in good yields via C–N cleavage (Scheme 25) [61]. The active Pd0 species was inserted into the carboxylate group to afford the

• nitrilium salt 92 followed by carboxylate attack (93) and Mumm rearrangement (Scheme 27) [63]. Furthermore, Maruoka and co-workers (2020) developed a one-pot transamidation reaction catalyzed by Cu via acid fluoride 48 (Scheme 28) [64]. In this work, single-electron transfer (SET) between Selectfluor and

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• from direct photoreactivity [24][25], sulfonium salts can be easily reduced under photoredox-catalyzed conditions [20][21][22], and the resulting radical undergoes homolytic cleavage of one of the C–S bonds, releasing an aryl radical Ar• and a diaryl sulfide Ar2S. Subsequently, triarylsulfonium ions

• (whose EREDonset value were in the range −1.60 and −1.92 V vs Ag/AgCl, a set comparable to that reported in the literature for fac-Ir(ppy) [37], which was effectively used in the photoredox-catalyzed reduction of sulfonium salts [29]) and derivatives 1a–d (EAr3S+/Ar3S• = −1.35 to −1.46 V vs Ag/AgCl; see

• types of CDs and aims to promote the use of these sustainable materials, it opens the way for further exploitation of such compounds in visible-light-catalyzed reactions. UV–vis spectra of the CDs. All the measurements have been performed in water, except for CD-a-GLU, where a H2O/acetonitrile 1:1

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• Advanced Academic Research (IAAR), Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan 10.3762/bjoc.21.83 Abstract In this study, we implemented the P,olefin-type chiral ligand (aR)-(−)-6, which contains a cyclohexyl group and a cinnamoyl group on the nitrogen atom, in the Pd-catalyzed

• palladium catalysts with amines as nucleophiles have been reported [14][15][16][17][18][19][20][21][22][23][24][25], there have been only a few reports on the N-substitution of isatin using asymmetric methods. Recently, Wolf’s group reported a transition-metal-catalyzed (Pd-catalyzed) asymmetric allylic

• ligands with axial chirality for Pd-catalyzed asymmetric allylic substitution reactions. For example, the Zhou group reported a P,olefin-type chiral ligand 3 with C–C bond axial chirality for this reaction (Figure 2) [27]. Additionally, we have recently reported chiral ligands with C–N bond axial

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

• the terminal alkene and the conformational strain of forming a bridge[3.2.1]bicycle might be responsible for a selective 6-exo-trig cyclization. From tricyclic compound 4, anti-Markovnikov oxidation catalyzed by palladium led to the formation of aldehyde 5. When treated with p-TsOH, the intramolecular

• annulation and applied it in the divergent total synthesis of Cephalotaxus alkaloids (Scheme 3) [22], including cephalotaxine whose ester, homoharringtonine, has been listed as an approved FDA drug for the treatment of chronic myeloid leukemia [23]. In their elegant study, an Au-catalyzed [2 + 3] annulation

• -catalyzed asymmetric [2 + 3] annulation of tertiary enamides with enoldiazoacetates, enabling highly efficient total syntheses of Cephalotaxus alkaloids (Scheme 4) [27]. In their recent study, the homopiperonyl alcohol 26 was transformed into tricyclic enamide 28 in five steps in a decagram scale. As no

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

• iodine should break the symmetry; however, no effect on the absorption spectra and especially on the lower energy |D1⟩ transition has been reported [45]. Interestingly, substitution of one of the para-chlorines in TTM by iodine (I-TTM) has been reported to enable Pd-catalyzed cross-coupling, allowing

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

• followed by interception of the lithium enolate with PhNTf2 to give enol triflate 25 in 59% overall yield. The following palladium-catalyzed methoxycarbonylation produced methyl ester 26 in a satisfactory yield of 84%. TIPS-protected allylic alcohol 28 was selected as the appropriate precursor for the α,β

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

• ) triflate-catalyzed post-Ugi assembly of novel pyrazolo[1,5-a][1,4]diazepine scaffolds is reported offering high yields (up to 98%) under mild conditions. The synthetic sequence involves the Ugi four-component reaction (U4CR) of pyrazole-3-carbaldehydes, primary amines, 3-substituted propiolic acids, and

• isocyanides, followed by a silver(I) triflate-catalyzed intramolecular heteroannulation of the resulting pyrazole-tethered propargylamides occurring in a 7-endo-dig fashion. The approach is scalable and tolerates a diverse range of substitution patterns. Keywords: heterocycles; post-MCR transformations

• employed the U4CR of ortho-halogenated benzaldehydes 7, primary amines 2, 3-substituted propiolic acids 8, and isocyanides 4 to synthesize propargylamides 9. These propargylic Ugi adducts 9 were subsequently subjected to a Cu-catalyzed tandem azide–alkyne cycloaddition/Ullmann coupling resulting in the

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

• control The precise regulation of product selectivity represents a fundamental challenge in transition-metal-catalyzed organic transformations, with significant implications for complex molecule synthesis. In this context, ligand-modulated divergent catalysis has emerged as a paradigm-shifting strategy

• , thereby offering unprecedented control over chemo-, regio-, and stereoselectivity parameters in catalytic manifolds. In 2015, the Jiang group developed a palladium-catalyzed regioselective three-component C1 insertion reaction (Scheme 1) [19]. In this reaction, an o-iodoaniline 1, phenylacetylene, and

• in steering catalytic selectivity. In 2016, the Jiang group achieved regioselective control in the gold-catalyzed intramolecular hydroarylation of alkynes by modulating the electronic and steric effects of ligands (Scheme 2) [20]. Mechanistically, the electron-deficient phosphite ligand L1 and the

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• carboboration of unsaturated hydrocarbons [1][2][3][4][5][6][7]. In the course of our investigation of the copper-catalyzed borylative coupling of alkynes with allylic gem-dichlorides [3], we observed that alkyl 4,4-dichloro-2-butenoates deviated from the general reactivity trend. While allylic gem-dichlorides

• mechanism for the copper-catalyzed diastereoselective dimerization of 4,4-dichoro-2-butenoic acid derivatives (Scheme 4). Initially, the LCu–pin complex generated through reaction between LCu–Ot-Bu and B2pin2 undergoes coordination and regioselective insertion into 1 giving rise to β-borylated organocopper

• functionalized cyclopropane scaffolds depending on the nature of the carboxylic acid derivative. Chemodivergent reactivity observed in copper-catalyzed borylative couplings of allylic gem-dichlorides. Cu-Bpin-mediated dimerization of 4,4-dichoro-2-butenoic acid derivatives. Control experiments. Proposed

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

• obtained (Table 1, entry 19). With the optimized conditions in hand, we explored the substrate scope of the CS@CuI-catalyzed cascade reactions of 2-halobenzoic acids (including 2-iodobenzoic acid and 2-bromobenzoic acid) with amidines (Scheme 2). Initially, when the amidine substituent (R2) is a methyl

• higher reactivity than 2-bromobenzoic acid derivatives. Based on previously reported literature [7][13], a mechanism for the copper-catalyzed formation of quinazolinones is proposed in Scheme 3. Initially, the 2-halobenzoic acid 1 coordinates with CS@CuI to form intermediate I in the presence of Na2CO3

• under optimized conditions (Scheme 4a). The recyclability of heterogeneous catalysts is a critical factor in assessing their practical utility in transition metal-catalyzed reactions. Therefore, the recyclability of CS@CuI was evaluated in the reaction of 2-iodobenzoic acid (1a) with 2a, as illustrated

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• Seeun Lim Teresa Kim Yunmi Lee Department of Chemistry, Kwangwoon University, Seoul 01897, Republic of Korea 10.3762/bjoc.21.63 Abstract This study introduces a highly selective hydrocyanation method based on copper-catalyzed hydroalumination of allenes with diisobutylaluminum hydride, followed

• with diverse functional groups [12][13][14]. Consequently, the development of selective and predictable strategies for the introduction of cyano groups into quaternary carbon frameworks has become necessary in organic synthesis. The transition-metal-catalyzed hydrocyanation of carbon–carbon double

• -system configuration promotes selective functionalization, enabling the synthesis of various complex products through a single transformation [17][18][19]. Therefore, allenes have become versatile intermediates in numerous transition-metal-catalyzed reactions [20][21]. Despite extensive studies on the

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

• on silver-catalyzed C–H phosphorylation revealed that variations in current intensity, frequency, and duty ratio influence product yield. To achieve optimal reactivity, the duty ratio must exceed 50%. Additionally, an analysis of silver deposition on carbon and platinum electrodes indicated that

New advances in asymmetric organocatalysis II

• Radovan Šebesta

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

• , or sulfur. The year 2000 is typically regarded as the birth of organocatalysis, which was at that time regarded as a new mode of action for chemical catalysts. In that year, List and MacMillan et al. published their landmark studies on proline- and imidazolidine-catalyzed aldol, Mannich, and

• , carbohydrates, or thiourea [5][6][7][8]. Going even more back in time, we shall recognize the work of Eder, Sauer, Wiechert, Hajos, and Parrish on the proline-catalyzed Robinson annulation in the 1970s [9][10]. In light of this, organocatalysis appears to be 50 rather than 25 years old. But is even that correct

• -catalyzed reactions and biocatalysis. In the past 25 years, organocatalysis has grown rapidly into a broad area of research, with industrial applications now being developed [16]. The usefulness of any idea or methodology is ultimately often measured by its applications. The robustness, reliability, as well

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• hydrocyanation of hydrazones, catalyzed by a calcium–BINOL phosphate complex, has been studied for the first time both experimentally and computationally with DFT methods. A full catalytic cycle for the enantioselective synthesis of α-hydrazinonitriles is proposed based on insights gained from DFT calculations

• ; hydrazones; isocyanides; Introduction Catalytic applications of non-toxic earth abundant metals like calcium are currently on the rise [1][2][3][4]. Prominent recent examples that witness the versatility of calcium catalysis include calcium-catalyzed amination of π-activated alcohols [5], the Beckmann

• in elucidating the mechanism by which these bifunctional compounds act as powerful catalysts [21][22][23][24][25][26][27][28][29]. Since Ishihara disclosed the crucial role of calcium in many purportedly purely organocatalytic BINOL phosphate-catalyzed reactions [30][31], several asymmetric synthesis

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

• report the copper-catalyzed synthesis of tetrahydroquinoline derivatives via a domino reaction of aniline with cyclobutanone oxime. This method demonstrates a selective approach for generating bioactive tetrahydroquinoline scaffolds, which have broad applications in pharmaceutical chemistry. The reaction

• 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

• stereocontrol (Scheme 1b) [24]. In 2023, Zeng et al. reported the first example of a chromium-catalyzed spirocyclization between anilines and cyclobutanones, providing direct access to medicinally relevant cyclobutane-annulated and structurally constrained spirotetrahydroquinoline (STHQ) scaffolds [25]. Given

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

• provide fluorophore 19. Subsequent palladium-catalyzed cross-coupling with tributyl(vinyl)tin resulted in the installation of the vinyl group (compound 20). Finally, cleavage of the silyl ether gave the free alcohol 21, which was converted into the corresponding mesyloxypropyl HBC ligand 22. The

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

• Abstract The transition-metal-catalyzed asymmetric allylic substitution represents a pivotal methodology in organic synthesis, providing remarkable versatility for complex molecule construction. Particularly, the generation and utilization of chiral secondary alkylcopper species have received considerable

• attention due to their unique properties in stereoselective allylic substitution. This review highlights recent advances in copper-catalyzed asymmetric allylic substitution reactions with chiral secondary alkylcopper species, encompassing several key strategies for their generation: stereospecific

• secondary organocopper; copper-mediated reaction; stereoselectivity; Introduction The transition-metal-catalyzed regio- and enantioselective allylic substitution represents a pivotal methodology in organic synthesis, providing remarkable versatility for complex molecule construction [1][2][3][4]. The

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• under Pd-catalyzed hydrogenolysis afforded diamino acid ester 14 (75% yield) that was likely formed by ring-opening of the unstable N-unprotected 2-aminoproline followed by the reduction of the open-chain imine tautomer. Likewise, the open-chain amino alcohol 15 was formed also upon the reduction of the

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

• disulfide bridges. More recently, Lang et al. developed an approach using dual photoredox/nickel-catalyzed antibody functionalization [45], demonstrating the selective modification of Cys residues through photocatalytic methods (Figure 7). A key advantage of this strategy lies in the use of readily

• procedure developed by Bräse et al. on photoinduced disulfide rebridging method. Schematic procedure developed by Lang et al. on a photoinduced dual nickel photoredox-catalyzed approach. The antibody shown in this figure is from https://www.gettyimages.de/detail/illustration/monoclonal-antibody-igg2a

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• alcohol 19 was isolated in 89% yield. The copper-catalyzed replacement of the bromine substituent in 19 with a hydroxy group was achieved in the presence of a catalytic amount of oxalamide ligand I [13]. This transformation is critical for enabling further functionalization and the reaction conditions

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• copper(I)-catalyzed reactions (48–71%) [13] and the four-component Ugi reaction [14] yields 48–71% and 27–67%, respectively. In addition, pyroglutamates with isocyanates, which provide exceptionally high yields (97–99%) [15], and dipeptides have been utilized in triflate-activated Mumm’s rearrangement

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

• , in a recent work, Pan et al. could chemoselectively oxidize methanol using a TEMPO-catalyzed electro-oxidation process, even in the presence of oxidizable amines, such as benzylamine, paving the way for the use of methanol as a formaldehyde surrogate in these isocyanide-based MCRs (Scheme 3) and

• compound and MMS, undergoes an aza-Diels–Alder cyclization with the alkyne, and after oxidation and aromatization steps generates quinoline II. Unfortunately, under these gentle and greener conditions, aliphatic alkynes remain unreacted, compared to the metal-catalyzed version developed by Xu et al. [37

• compound as no reaction is observed with aliphatic alkynes. Furthermore, the yields are between 50–80%, which are slightly lower than those under metal-catalyzed conditions. Nevertheless, these results open the door to further studies aimed at developing more efficient, non-catalyzed synthetic procedures

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

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

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• established by X-ray analysis. The proposed mechanism of the considered processes is outlined at Scheme 8. Initially, the free nitrogen nucleophile is reversibly generated from the corresponding hydrochloride or acetate. Next, acid-catalyzed addition of the amine component to the carbon atom of the aroyl

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

• -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

• enantio- and diastereoselective Mannich reaction of α-cyanoesters with aldimines catalyzed by chiral amines, which provided β-amino cyanoesters in excellent yield and diastereoselectivities with up to 98% ee (Figure 2a) [41]. The Mannich reaction has been also applied in the construction of contiguous