Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• , most synthetic methods have focused on the preparation of symmetric derivatives [12][13]. Traditional approaches, such as oxidative coupling of anilines [14][15][16][17][18][19], reductive coupling of nitroarenes [20][21][22][23], or cross-coupling between anilines and nitroarenes have proven

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• : a mixture of aniline 4 (0.3 mmol), alkyne 3 (0.6 mmol), [RuCl2(p-cymene)]2 (0.03 mmol), KPF6 (0.06 mmol) and NaOAc (0.06 mmol) in H2O/iPrOH (1:1, 6 mL), refluxing under electrolysis (RVC anode, Pt cathode, 10 mA) for 1.8–3.9 h. This reaction was compatible with anilines with either electron-donating

• . Indole skeletons were obtained successfully through electrochemical coupling of urea derivatives, dehydrogenative annulation of alkynes with anilines, annulation of o-arylalkynylanilines, cyclization of 2-ethynylanilines, selenocyclization of diselenides with 2-ethynylanilines, and enantioselective

• functional molecules possessing five-membered rings. Electrochemical intramolecular coupling of ureas to form indoles. Electrochemical dehydrogenative annulation of alkynes with anilines. Electrochemical annulations of o-arylalkynylanilines. Electrochemical cyclization of 2-ethynylanilines. Electrochemical

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• corresponding tetra-ortho-substituted atropisomeric anilines 49 in high yields with excellent enantioselectivities (Scheme 8b). In contrast, lactams possessing only one ortho substituent suffered from much lower reactivity (e.g., 49c), presumably due to the lack of sufficient torsional strain [50], whereas

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• axially chiral anilines [10][11] and a triazine molecule [9]. In particular, protonation of a remote basic site in N–C axially chiral anilines significantly increases the rotational barrier by attenuating resonance stabilization in the transition state. One important issue in this field is the development

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

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• obtained for product 3e derived from 3-tolylacetylene. However, the yield for compound 3f dropped to 60% because of the more sterically hindered 2-tolylacetylene. The domino C–N cross-coupling/hydroamination reaction of 3a–h with various anilines was studied next (Scheme 2) [28][29]. The conditions were

• result in a further improvement of the yield. With the optimized conditions in hand, the scope of the reaction was studied. The cyclization of alkynylated uracils 3a–h with various anilines afforded pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones 4a–m in moderate to good yields (Scheme 3). Various functional

• )-diones based on a domino C–N coupling/hydroamination reaction of readily available alkynylated uracils with anilines. The optimized reaction conditions allowed for the employment of various functional groups. The products revealed fluorescence properties which were influenced by the substitution pattern

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

• , and all substituted anilines afforded high yields of phosphoramidates. However, N-methyl- and N-ethylanilines showed lower yields and electron-donating groups led to a reduced yield compared to unsubstituted aniline. Further, KI performed best as the electrolyte and catalyst at 50 °C (Scheme 20). The

• even unprotected anilines participated in this reaction, yielding the desired product with a 72% yield. Furthermore, anilines bearing electron-donating groups such as methyl or weak electron-withdrawing groups like chlorine at the ortho position were efficiently involved in the electrochemical

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

• 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

• conditions, we proceeded to investigate the generality of this Cu-catalyzed system. Initially, a series of anilines bearing diverse substituents was examined, and the results are summarized in Scheme 2. When copper(II) trifluoroacetate was employed as the catalyst, para-halogen-substituted anilines 1b–e

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

• –Alder reaction between an imine and an alkene (Scheme 6). Very successfully, the multicomponent version of the Povarov reaction using aldehydes, anilines, and alkenes has been explored in a three-component cascade reaction to quinolines [28][29][30][31] (Scheme 6). Furthermore, protocols have been

• separation processes are required [32][35][36]. In this context, DMSO has been used as an alternative to formaldehyde for the MCR synthesis of a wide variety of quinolines and related compounds. For example, Zhang et al. showed that starting from anilines and substituted styrenes while using K2S2O8 for the

• substituted styrene under copper(I) catalysis to give the target compounds via a Povarov reaction. A further aromatization process yields product I (Scheme 8, path I). In a closely related approach, the same group reported on the synthesis of quinolines from anilines and alkynes [37]. In this case, the alkyne

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

• considered transformation using 2H-furo[3,2-b]pyran-2-ones 1 without electron-donating substituents at the aromatic ring. Also, the considered protocol failed for interactions of furanone 1a with diverse anilines. In this case a complex mixture of products was obtained after 24 h reflux in AcOH (Scheme 2d

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

• redox properties similar to those of squaraine derivatives, enabling key transformations such as the cyclization of anilines with maleimides and the reduction of Umemoto salts for trifluoromethylation of alkenes. With an excited-state reduction potential around 0.80 V, 46 demonstrates the capability to

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• condensation of carboxylic acids with anilines, often promoted by activating agents such as thionyl chloride or peptide coupling agents [86][87][88][89]. However, these protocols rely on environmentally harmful reagents and produce unwanted byproduct wastes. Recently, the research group of Son showcased a

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• primary anilines using a copper catalyst and dual Cu-electrode system to form C–N bonds (Figure 19) [79]. This catalytic system demonstrates a broad substrate scope, including electron-deficient boronic acids, which are typically regarded as challenging substrates because of their low reactivity in Chan

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• the triple bond furnishes the furo-ring and the final oxidation affords the tricyclic product 22. Substituted quinolines 23 were obtained in a convenient solvent-free multicomponent reaction starting from electron-rich or electron-poor anilines, alkyl or arylaldehydes and terminal alkynes, performing

• obtain cyclic ether-fused tetrahydroquinolines 24 has been reported starting from secondary anilines, cyclic ethers and paraformaldehyde (Scheme 18) [35]. In addition to Cu(OTf)2 as a catalyst, the most effective reaction conditions required a substoichiometric amount of p-nitrobenzoic acid as an

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

• be carried out in a one-pot fashion with comparable results and without significant variation from the two-step procedure. Utilization of the Povarov reaction and subsequent oxidation by DDQ was also done by Wang et al. in 2020 [54]. In situ-formed imines from anilines 91 and benzaldehydes 92 were

• a gram scale gave the product with analogous yield and enantioselectivity (73%, 96% ee). Hydrogen-bond-stabilized axially chiral N-arylquinones 133 were prepared by reaction of quinone esters 131 with anilines 132 mediated by CPA (R)-C23 (Scheme 39) [67]. Apart from respectable yields and remarkable

• it with another aromatic moiety such as phenyl or 2-thiophenyl led to no product being formed. An organocatalytic atroposelective three-component cascade heteroannulation was done by Wang et al. [87]. It was a reaction of ketoesters 192, anilines 193, and cyclohexadiones 194 catalyzed by SPINOL

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

• obtain α-acylaminoamides. Innovation in recent years with alternative reagents, like N-hydroxyimides or nitric acid in place of an acid, N-alkylated hydrazines, or nitrobenzene derivatives (reduced in situ to anilines) instead of amines, and in situ-prepared isocyanides, makes it a versatile method for

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

• ) using substituted anilines 101 and t-BuONO (Figure 18). The reactions were conducted under light irradiation (blue light/sunlight) for 30 minutes in DMSO within an inert atmosphere. All corroles demonstrated catalytic activity with only 0.5% loading, while control experiments without a catalyst or light

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

• of β-16a with 3-acetoxy-5-chloroindole. Anomerically pure indirubin-N-glucoside β-18a, indirubin-N-riboside β-19a, indirubin-N-galactoside β-20a, and indirubin-N-mannoside β-21a were prepared in good yields starting from the corresponding sugars and anilines [12][13]. In case of the indoxyl moiety

• corresponding acetyl-protected N-glycosyl anilines with oxalyl chloride was not possible. The failure of this reaction can be explained by electronic deactivation of the aromatic ring and steric hindrance which resulted in competing Claisen-type side-reactions of the acetyl groups. However, reactions of

• pivaloyl-protected N-glycosyl anilines also proved to be unsuccessful, which pointed to steric reasons. Therefore, we studied in our group the use of the less sterically hindered formyl instead of acetyl or pivaloyl protective groups. The reaction of glucose (22a) with aniline afforded anomerically pure N

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• efficient methods for the synthesis of heterocycles by multicomponent processes and domino reactions [16][17][18][19][20], here we disclosed the oxidative one-pot four-step synthesis of 2-amino-3,3’-spiroindolenines using readily available tertiary amines, electron-rich anilines and isocyanides as starting

• -pot multistep synthesis of unprecedent 2,3-diaminoindolenines using graphene oxide (GO) as heterogeneous catalyst [21]. The protocol involves the three-component Ugi (3C-Ugi) reaction between aldehydes, isocyanides and 2 equivalents of electron-rich anilines to give α-aminoamidines, which undergo a C

• two anilines are incorporated in the final product, we speculated that the diversification of them could lead to different products. Anyway, first attempts to use two different anilines in the reaction failed, giving complex mixtures of α-aminoamidines even using sequential or slow addition of

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

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• the possible substitution patterns, meta-substituted anilines hold a special place. These compounds are difficult to access due to the inherent ortho-/para-directional reactivity of the amino group, at the same time they are widely used in medicinal chemistry, resulting in several marketed drugs

• key fragment [17][18][19][20][21][22][23][24][25][26]. The aforementioned features have led to an extensive development of novel methods to access meta-substituted anilines which can be divided into two main strategies (Scheme 1A) [27]. The first strategy focuses on the decoration of the aromatic ring

• situ-generated acetone imines in a (3 + 3) manner to afford meta-substituted anilines (Scheme 1C) [53][54]. Various EWGs (ester, carbamoyl, ketone, trifluoromethyl) have been successfully employed which motivated us to evaluate other possible EWGs. Results and Discussion Based on the fact, that many

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• ][16], anilines [17], carbonyls [18][19][20][21], propargyl/allylsilanes [22][23][24][25][26][27][28][29][30][31][32][33][34], ynamides [35][36][37], and alkyl nitriles [38][39][40], were found to be suitable for this process. Whereas the addition of fluorine atoms to molecules is a well-established

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• ]. Synthesis of pyrazolo[4,3-c]quinoline derivatives [40]. Synthesis of 1,3,4-oxadiazoles and Δ3-1,3,4-oxadiazolines [41]. Synthesis of 1,3,4-oxadiazoles [43]. Synthesis of 2-(1,3,4-oxadiazol-2-yl)anilines [44]. Synthesis of fused s-triazolo perchlorates [45]. Synthesis of 1-aryl and 1,5-disubstitued 1,2,4

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• has been successfully applied as photoredox catalyst in the synthesis of secondary or primary anilines via light-dependent desulfonylation or desulfonylation/dealkylation procedures [19]. Thus, the design of novel and efficient routes for the synthesis of 5-aryldeazaalloxazines 2 has become a

• (1H,3H)-dione) by refluxing with thionyl chloride [20][23]. However, the preparation of partially hydrogenated 5,10-dihydropyrimido[4,5-b]quinolinediones has been repeatedly reported by one-pot condensation of substituted anilines, aldehydes and barbituric acids, usually in protic solvents (alcohols

• of photocatalysts by tuning their redox and photophysical properties. Thus, we successfully developed a one-pot, three-component synthetic method with those substituents in 5-aryldeazaflavins 1 on the deazaisoalloxazine core or on the phenyl ring by condensation of N-substituted anilines, aromatic