3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• reactions of intermolecular annulation of a variety of non-aromatic five- [4][5][6] and six-membered carbo- and heterocycles [7][8][9] with azirines, which occur under transition metal catalysis or photocatalysis. Annulation of the pyrrole ring to an aromatic system is limited to reactions of functionalized

• heteroaromatic system have been reported to date. The formation of dihydrobenzofuro[3,2-b]pyrrole cycloadducts as by-products has been observed in the synthesis of aziridines by the transition metal-catalyzed reaction of benzofurans with 3-arylazirines [16]. This paper presents the use of azirines as annulation

• discussed. Results and Discussion Guided by the known fact that 3-arylazirines in the presence of transition metal compounds are sensitive to the enol form of 1,3-dicarbonyls [5][17][18][19], we chose for our study methyl 3-hydroxybenzo[b]thiophene-2-carboxylate (1) as an aromatic substrate having a 1,3

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• important transformation exhibiting higher chemical and environmental safety. Keywords: alternative solvent; click chemistry; cycloaddition; CyreneTM; 1,2,3-triazoles; Introduction In the past few decades, transition-metal-catalyzed coupling and addition reactions have represented one of the most powerful

• it is negative in the Ames test [25]. Recently, we determined key physicochemical properties of CyreneTM and showed that it has a negligible vapor pressure (<9.6 kPa) and low viscosity (<6.8 mPa·s) at typical transition-metal-catalyzed reaction temperatures (30–140 °C) [26]. CyreneTM has been

• obtained for Cu sources in different solvent systems [40][41]. Although CuAAC reactions can be efficiently performed in water, the moisture content of the organic reaction environment could have a significant effect on the efficiency of a transition-metal-catalyzed reaction. Because CyreneTM is fully

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• the reactivity of unsaturated esters towards an aza-Michael addition is the use of transition metal complexes as catalysts/promoters [40][41][42]. Considering this background, we reasoned that Ni(II) could be a suitable catalyst for the amination of unsaturated systems. Initial investigations were

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• , decarboxylative functionalizations, and Chan–Lam coupling reactions. In doing so, the authors point out the combination of transition-metal catalysis and electrochemistry as an efficient, sustainable method for the oftentimes challenging formation of C–C and C–heteroatom bonds in complex molecules. Another Review

• , Burley, Watson, and co-workers present a new synthesis of germyl triazoles from germyl alkynes through a copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction [6]. The resulting Ge-substituted triazoles could be further diversified. For example, through chemoselective transition-metal-catalyzed

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• -amination of benzoxazoles by transition-metal-catalysed reactions that traditionally involve aryl halide scaffolds [11][12][13][14]. However, these procedures entail disadvantages that need to be overcome if green chemistry criteria are to be met; high temperatures, long reaction times, the need for ligands

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• stimuli-responsive chiral electrochromic materials. In the same year, You’s group developed a transition-metal-catalyzed C–H/C–H-type regioselective C3-arylation of benzothiophenes using molecular oxygen as the oxidant [79]. This strategy afforded the TADF-active compound 64a, which exhibits efficient

• ), pronounced chiroptical activity (|gabs| = 0.0054–0.0056), and substantial ΦF of 0.21–0.32 under both neutral and acidic conditions. This work exemplifies the power of transition-metal catalysis for constructing enantioenriched helicenes with tunable photophysical properties. These contributions from 2021

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• molecules. On the other hand, C–H bonds exhibit low reactivity due to their relatively high bond dissociation energy (BDE) (Figure 1a). Therefore, the direct functionalization of C–H bonds is extremely challenging [1][2][3][4][5]. In recent decades, transition-metal-catalyzed C–H bond functionalization

• principles. (a) BDE of C–H. (b) Direct functionalization of C–H catalyzed by transition-metal. (c) Direct functionalization of C–H via HAT process. (a) Amidyl radical-enabled hydrogen atom transfer. (b) Substituent effects to amidyl radical properties. (c) This review: generation of amidyl radical and

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• a specific focus on strategies involving carbon-centered radicals. The reactions are systematically categorized according to their initiation modes and radical sources, including (1) transition-metal-catalyzed radical reactions, (2) peroxide-mediated thermal processes, (3) photoredox-catalyzed

• catalysts for generating trifluoromethyl radicals, thereby eliminating the need for expensive transition-metal catalysts and external oxidants, which enhances both the economic and environmental benefits of the process. Furthermore, the research demonstrated the method's broad applicability across various N

• oxidation, ultimately forming the final oxindole product 76a. Interestingly, the reaction proceeds via two distinct pathways depending on the presence of an alkene radical acceptor, with DMSO or dimethyl sulfone as the byproduct. In addition to transition-metal and photocatalyzed systems, several metal-free

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• , which generally employed stoichiometric amounts of oxidants or more expensive transition metal catalysts, the present protocol employs only cheap copper sulfate pentahydrate as a catalyst under mild reaction conditions. The achieved phosphorylation proceeds via the formation of P-centered radicals

• oxyphosphorylation of styrenes [40], this strategy was further extended [41] to phenylacetylenes [42][43][44], cinnamic [45][46][47][48] and α,β-alkynyl carboxylic acids [42], and vinyl azides [49][50] (Scheme 1a). As a rule, transition metal catalysts (Fe [42][44][51][52], Cu [42][44][46][51][53], Ag [54], Mn [55

• product was observed. Other transition metal salts were also ineffective in the discovered transformation (Table 1, entries 18–20). With optimal conditions in hand, the scope of the developed phosphorylation protocol was evaluated (Scheme 2). The discovered phosphorylation is applicable to various

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• activation, transforming these inert bonds into reactive carbon–transition metal (C–M) bonds. Subsequent transformations of these complexes enable the formation of an array of new functional groups, such as carbon–carbon and carbon–heteroatom bonds, underpinning a plethora of synthetic applications

• whether the connectivity has changed. The connectivity of the complex before and after optimization is compared only for bonds not involving the transition metal since the determination of bonds to transition metals is prone to errors. Instead, the geometry of the four atoms adjacent to the transition

• metal (the two oxygen atoms from the acetate moiety, the carbon atom from the reaction site, and the heteroatom from the directing group) is analysed without regard for connectivity. All four atoms have to lie within a plane after the optimization for the optimization to be considered successful. This

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• aryl modifications in C6 position by utilising the chiral pool of a non-proteinogenic amino acid in combination with transition metal-catalysed cross-coupling reactions. Moreover, we present an in-depth NMR analysis of the key intermediate steps, which illustrates the conformational constraints in

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

• release (82). Numerous cinnamic acid derivatives with electron-withdrawing and -donating groups were converted to the corresponding amides 76–81 in moderate to excellent yields (Scheme 24B) [60]. 2.1.2 Transition-metal catalysis: Several transition metals have been exploited to catalyze O/N-acylations of

• -abundant transition metal, Patel and Patel (2020) utilized a Ni salt of phosphomolybdic acid (NiHPMA) to synthesize methyl cinnamate (44) from cinnamaldehyde (162) via a reactive peroxo species 165 (Scheme 53) [94]. Beyond transition metals, metal-free oxidative esterifications, such as carbene-based

• source to perform the Pd-catalyzed alkyne hydrocarbonylation with CO via 276 to obtain the corresponding cinnamic acids 273–275 in good yields (Scheme 68B) [117]. In addition, a gram scale operation has been carried out. Li and co-workers (2019) employed a non-precious transition metal, ligand-free Fe3

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

• + species, a process where transition-metal-based complexes are employed [29], often (in the case of Ru(II)-based derivatives) in the presence of tertiary amines as sacrificial reductants [27][28]. Nonetheless, while this work serves primarily as a preliminary study comparing the reducing power of various

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

• 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

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

• formation of the tricyclic triazolo[1,5-a][1,4]benzodiazepine scaffold 10 (Scheme 1b) [39]. Triple bond-containing Ugi adducts showed a great promise for the assembly of various seven-membered nitrogen-containing heterocyclic cores through transition-metal-catalyzed alkyne hydroarylations [40][41][42][43

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

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

• cyclobutyldiol. A) Product derivatization and B) transition-metal EnT catalysis. Reaction conditions A): 4d (1 equiv), H2O2 (30 wt % in H2O), aq NaH2PO4, THF, 0 °C; B) 4 (1 equiv), KF (4 equiv), ʟ-tartaric acid (2.1 equiv), MeOH, MeCN, H2O, rt. Probing EnT catalysis of alkenylboronic ester 1a via alkene

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

• 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

• 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

• derivatives of glycine with diarylphosphine oxide (R2P(O)–H) for the synthesis of 1-aminoalkylphosphine oxides without the use of any transition metal catalyst or external oxidant. In this conversion, 1-aminoalkylphosphine oxides were formed in an undivided cell using a carbon electrode as the anode and

• first due to its lowest oxidation potential among the species. In 2024, Zhu et al. [63] reported an electrochemical transition-metal and additive-free synthesis of phosphorylated propargyl alcohols at room temperature. The reaction is carried out in an undivided cell using glassy carbon (GC) as an anode

• 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

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

• 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

• dialkylzinc reagents as nucleophiles [26]. They subsequently expanded the methodology by successfully employing triorganoaluminum reagents [27]. Recent developments in transition-metal-catalyzed AAA have increasingly turned to organoboron compounds [28][29][30][31]. These reagents offer numerous advantages

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

• particularly useful and important tool in which azides and other dipolar species engage with reactive alkenes and alkynes on non-canonical amino acids [20]. Transition-metal-mediated processes, including metathesis reactions, aryl cross-coupling reactions, and conjugate addition reactions with dehydroalanine

• emerged as a transformative approach in the modification of proteins, enabling researchers to achieve selective and efficient conjugation under mild conditions [37]. By utilizing visible light and transition-metal catalysts, this technique allows the generation of reactive intermediates that can

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

• traps the sulfonium ylide (Scheme 16). In an independent work, Mhaske et al. proposed an alternative methodology to furnish β-amino ketone 20a (Scheme 17), using DMSO as a formaldehyde surrogate but with activation via ammonium persulfate (APS), avoiding the use of transition-metal catalysis [51]. In

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

• used to achieve higher yields [27]. Even in the absence of a transition-metal-based photosensitizer, a recent study showed that perfluoroalkylation using perfluoroalkyl iodides (RFI) could be carried out by activation of the RF–I bonds by formation of electron donor–electron acceptor complexes with an